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CAS No. : | 5497-67-6 | MDL No. : | MFCD00010699 |
Formula : | C7H12O | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | DXSDIWHOOOBQTJ-UHFFFAOYSA-N |
M.W : | 112.17 | Pubchem ID : | 79636 |
Synonyms : |
|
Signal Word: | Danger | Class: | 3 |
Precautionary Statements: | P210-P233-P240-P241-P242-P243-P261-P264-P270-P271-P273-P280-P301+P312+P330-P303+P361+P353-P304+P340+P312-P305+P351+P338-P332+P313-P337+P313-P370+P378-P403+P233-P403+P235-P405-P501 | UN#: | 1989 |
Hazard Statements: | H225-H302-H315-H319-H335-H402 | Packing Group: | Ⅱ |
GHS Pictogram: |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With aluminum oxide; palladium/alumina Hydrogenation; | ||
With hydrogen | ||
With hydrogen In ethanol |
(hydrogenation); | ||
With hydrogen In ethanol Ambient temperature; | ||
With (bis(mesityl-benzimidazol-2-ylidene)phenyl)Co(N<SUB>2</SUB>)(PPh<SUB>3</SUB>); hydrogen In benzene-d6 at -196.16 - 19.84℃; for 22h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With methanol; nickel at 125℃; Hydrogenation; | ||
Multi-step reaction with 2 steps 1: lithium aluminium hydride 2: H2 / Pd/C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With lithium aluminium tetrahydride In diethyl ether for 3h; Heating; | |
95% | With sodium tetrahydroborate In methanol at 0℃; | |
90% | With lithium aluminium tetrahydride In diethyl ether for 2h; Heating; |
90% | With sodium tetrahydroborate; sodium hydroxide In methanol; water at 25℃; for 10.5h; | 2,2-Dimethylpent-4-en-1-ol To a solution of aldehyde 12 (40.0 g, 0.35 mol) in MeOH (400 mL) was added a solution of sodium borohydride (4.8 g, 0.13 mol) in 0.2 M aqueous NaOH (60 mL) slowly over 30 min. The resulting solution was stirred at 25 °C for 10 h, concentrated on a rotary evaporator, diluted with aqueous 10% NH4Cl solution (50 mL), and extracted with diethyl ether (3 × 100 mL). The combined organic layers were washed with water and brine, dried (MgSO4), concentrated, and column chromatographed on silica gel using a mixture of hexane and diethyl ether(1:1) as eluent to give 2,2-dimethylpent-4-en-1-olYield: 38 g (90%); colorless oil. 1H NMR (400 MHz, CDCl3): = 5.94-5.82 (m, 1 H, =CH), 5.07-5.04 (m,2 H, =CH2), 3.34 (s, 2 H, CH2O), 2.03 (d, J = 8.0 Hz, 2 H, CH2), 0.89 (s, 6H, 2 CH3). |
89% | With lithium aluminium tetrahydride In diethyl ether at 0℃; for 0.5h; | 24 A solution of lithium aluminium hydride in diethyl ether (1M, 15.75 ml) was added dropwise to an ice-bath cooled and stirred solution of 2,2-dimethyl-4-pentenal (3.528 g, 31.5 mmol) in diethyl ether (20 ml). The mixture was stirred for 30 min. and carefully quenched with 4M NaOH (30 ml). The mixture was extracted into diethyl ether. The combined organic extracts were dried (Na2SO4) and concentrated to give the title product (3.2 g, 89%). [0210] δH (400 MHz, CDCl3): 5.85 (1H, m), 5.05 (2H, m), 3.33 (2H, s), 3.65 (2H, m), 2.02 (2H, d, J 7.4 Hz), 1.47 (1H, br), 0.89 (6H, s). |
80% | With sodium tetrahydroborate In methanol at 0 - 20℃; for 1h; | |
78% | With sodium tetrahydroborate | |
73% | With lithium aluminium tetrahydride In diethyl ether Reflux; | |
72% | With sodium hydroxide; sodium tetrahydroborate In ethanol at 20℃; | |
With potassium hydroxide | ||
With sodium tetrahydroborate | ||
40 g | With sodium tetrahydroborate In ethanol; water | |
With lithium aluminium tetrahydride | ||
With sodium tetrahydroborate | ||
With sodium tetrahydroborate In methanol at 0 - 20℃; | ||
With sodium tetrahydroborate In methanol at 0 - 20℃; for 1h; | ||
With lithium aluminium tetrahydride | ||
With sodium tetrahydroborate In tetrahydrofuran; dichloromethane; water | 11 Synthesis of 2,2-dimethyl-4-pentenol EXAMPLE 11 Synthesis of 2,2-dimethyl-4-pentenol In a dry box, 5 g 2,2-dimethyl-4-pentenal was mixed with 40 mL anhydrous THF. NaBH4 (3.376 g) was added in portions. Soon the solution became hot. More THF was added to lower the temperature. The mixture was stirred overnight at RT. The flask was taken out of the dry box. Water and CH2Cl2 were added to the mixture. The CH2Cl2 layer was separated, washed with water twice and dried with Na2SO4. Evaporation of CH2Cl2 gave 4.3 g pure product. 1H NMR(CDCl3): δ 1.00 (s, 6H, -CMe2-); 2.15 (d, 2H, CH2=CH-CH2-); 3.44 (s, 2H, -CH2OH); 5.15 (d, 2H, CH2=CH-); 5.95 (m, 1H, CH2=CH-). | |
i 4,4-Dimethyl-5-methoxypentanal i) 2,2-Dimethylpent-4-en-1-ol was prepared from 2,2-dimethylpent-4-enal (supplied by Aldrich) using methodology described in stage (iv) of Process P. | ||
Stage #1: 2,2-dimethyl-4-pentenal With sodium tetrahydroborate In ethanol at 20℃; Stage #2: With sodium hydroxide; water In tetrahydrofuran at 0℃; | 24.A Alternatively, the title compound (24a) was prepared in comparable yield starting from the corresponding alkyl esters of acid employing comparable synthetic methods, or from commercially available 2,2-dimethyl-4-pentenal through reduction of the aldehyde functionality with sodium borohydride (NaBH4) in ethanol (EtOH) at room temperature. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With toluene-4-sulfonic acid In various solvent(s) for 48h; Heating; | |
92% | With toluene-4-sulfonic acid at 150℃; for 36h; | 2,2-dimethylpent-4-enal (5) To a one-liter single-necked flask equipped with a magnetic stirring bar were added 275 mL (216 g, 3.0 mol) isobutyraldehyde, 140 mL (116 g, 2.00 mol) allyl alcohol, and 0.8276 g (4.2 mmol) p-toluenesulfonic acid monohydrate as a catalyst, and 500 mL p-cymene. The reaction flask was fitted with a 24 in. vigreux column and a 30 mL Dean-Stark tap equipped with a reflux condenser on top of the trap. The reaction was heated to 150 °C for 36 hrs. and 30 mL of H2O were collected. The reaction was then cooled to 100 °C while the Dean-Stark trap and reflux condenser were replaced with a distillation head. The mixture was then distilled, with the fraction that came at 120 °C (1 atm) collected, to yield the title compound (206.37 g, 92% yield) as a clear liquid. 1H NMR (500 MHz): 1.07 (s, 6H), 2.22 (d, 2H, Ja = 8 Hz), 5.09 (dd, 2H, Ja = 8 Hz, Jb = 10 Hz), 5.72 (td, 1H, Jc = 3 Hz, Jb = 10 Hz), 9.49 (s, 1H). 13C NMR (133 MHz): 21.32, 41.60, 45.87, 118.60, 133.27, 206.03. |
90% | With toluene-4-sulfonic acid In 1,3,5-trimethyl-benzene at 220℃; for 48h; Dean-Stark; | 2,2-Dimethylpent-4-enal (12) To a round-bottom flask equipped with a Vigreux column (30 cmlength), a Dean-Stark apparatus, and a reflux condenser, were addedallyl alcohol (21.7 g, 0.375 mol), isobutyraldehyde (40.5 g, 0.56 mol),p-toluenesulfonic acid (0.125 g, 6.5 mmol) and mesitylene (70 mL).The solution was stirred and heated at 220 °C for 48 h, and during thistime water was collected in the Dean-Stark apparatus. The solution was cooled to 25 °C and distilled under normal pressure to give aldehyde12.Yield: 40 g (90%); colorless liquid; bp 124-125 °C/760 mm (Lit.27 124-126 °C).1H NMR (400 MHz, CDCl3): = 9.50 (s, 1 H, CHO), 5.77-5.67 (m, 1 H,=CH), 5.11-5.06 (m, 2 H, =CH2), 2.23 (d, J = 7.6 Hz, 2 H, CH2), 1.07 (s, 6H, 2 CH3). |
89% | With 1,1'-bis-(diphenylphosphino)ferrocene; bis(1,5-cyclooctadiene)nickel (0) In methanol at 80℃; for 16h; Inert atmosphere; Schlenk technique; Glovebox; Sealed tube; | |
78% | With toluene-4-sulfonic acid for 32h; Heating; Dean-Stark; | |
73% | With 4-methylisopropylbenzene; toluene-4-sulfonic acid for 32h; Reflux; Dean-Stark; | |
73% | With toluene-4-sulfonic acid for 32h; Reflux; Dean-Stark; | 2.1 4.2.1. 2,2-Dimethylpent-4-enal (24) Freshly distilled isobutyraldehyde (108 g, 1.5 mol) and allyl alcohol (58.0 g, 1.0 mol) were added to a solution of p-toluenesulfonic acid (0.25 g) in p-cymene (200 g). The mixture was heated to reflux for 32 h under a Dean-Stark trap until no more water was separated and a sump temperature of about 140 °C was reached. After vacuum distillation (76 °C at 200 mbar) through a 50 cm Vigreux column the aldehyde (81.4 g, 0.73 mol, 73%) was obtained as a colourless liquid. 1H NMR (CDCl3, 200 MHz): δ = 9.47 (s, 1H), 5.60-5.70 (m, 1H), 5.01-5.05 (m, 2H), 2.21 (d, J = 7.3 Hz, 2H), 1.05 (s, 6H) ppm; 13C NMR (CDCl3, 50 MHz): δ = 205.9, 133.1, 118.4, 45.7, 41.4, 21.1 ppm. These data are consistent with published data. 18 |
73% | With toluene-4-sulfonic acid for 32h; Dean-Stark; Reflux; | 2,2-Dimethylpent-4-enal (6) Freshly distilled isobutyraldehyde (108 g, 1.5 mol) and allyl alcohol (58.0 g, 1.0 mol) were added to a solution of p-toluenesulfonic acid (0.25 g) in p-cymene (200 g). The mixture was heated to reflux for 32 h under a Dean-Stark trap until no more water was separated and a sump temperature of about 140 °C was reached. After vacuum distillation (76 °C at 200 mbar) through a 50 cm Vigreux column the aldehyde (81.4 g, 0.73 mol, 73%) was obtained as a colourless liquid. 1H NMR (CDCl3, 200 MHz,): δ = 9.47 (s, 1H), 5.60-5.70 (m, 1H), 5.01-5.05 (m, 2H), 2.21 (d, J = 7.3 Hz, 2H), 1.05 (s, 6H) ppm; 13C NMR (CDCl3, 50 MHz): δ = 205.9, 133.1, 118.4, 45.7, 41.4, 21.1 ppm. These data are consistent with published data (Lit.: Brannock, K. C. J. Am. Chem. Soc. 1959, 81 (13), 3379-3383). |
73% | With toluene-4-sulfonic acid at 140℃; Dean-Stark; | |
72% | With toluene-4-sulfonic acid In 4-methylisopropylbenzene for 24h; Reflux; | |
60% | With 4-methylisopropylbenzene; toluene-4-sulfonic acid at 140℃; for 72h; Inert atmosphere; Schlenk technique; Dean-Stark; | |
With 4-methylisopropylbenzene; toluene-4-sulfonic acid | ||
(i) CaCl2, (ii) aq. H3PO4; Multistep reaction; | ||
With 4-methylisopropylbenzene; toluene-4-sulfonic acid | ||
With toluene-4-sulfonic acid In various solvent(s) for 32h; Heating; | ||
With toluene-4-sulfonic acid In 4-methylisopropylbenzene for 36h; Heating / reflux; | 6.A A 2-L round-bottom flask was charged with p-cymene (800 mL), allylic alcohol (290 mL, 4.27 mol), isobutyraldehyde (588 mL, 6.40 mol), and p-toluenesulfonic acid (2 g). The flask was fitted with a Dean-Stark apparatus, and the mixture was refluxed for 36 hours to remove water azeotropically. The Dean-Stark apparatus was removed and replaced by a Rashig-ring packed column. The mixture was distilled to collect the fraction at 93-135 0C. The distilled fraction was washed with water to remove allyl alcohol, dried over sodium sulfate, filtered and redistilled. The fractions distilled before 180 0C were discarded, and distillate at 180-205 0C was collected to give the title compound as a yellow oil. | |
With toluene-4-sulfonic acid In 4-methylisopropylbenzene Reflux; | ||
With toluene-4-sulfonic acid In Isopropylbenzene at 150℃; Inert atmosphere; | ||
With 1,1'-bis-(diphenylphosphino)ferrocene; bis(1,5-cyclooctadiene)nickel (0) In methanol at 80℃; for 15h; Schlenk technique; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With carbon monoxide In 1,2-dimethoxyethane at 150℃; for 24h; Yield given. Yields of byproduct given. Title compound not separated from byproducts; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With oxygen; copper(l) chloride; palladium dichloride In water; N,N-dimethyl-formamide for 1h; Ambient temperature; | |
66% | With oxygen; copper dichloride; palladium dichloride In water; N,N-dimethyl-formamide at 20℃; for 72h; | 2,2-dimethyl-4-oxopentanal (6) To a three-liter three-necked flask equipped with a stirring bar, reflux condenser, and fretted aerator connected to a compressed air line were added 206 g (1.84 mol) of 2,2-dimethylpent-4-enal (4) was dissolved in 1650 mL DMF and 650 mL H2O. To this mixture, 32.85 g (244.3 mmol) CuCl2 and 1.20 g (6.76 mmol) PdCl2 were added to the reaction mixture. Air was then sparged through the solution at room temperature while the condenser was cooled with cold water for 72 hrs., to prevent the evaporation of product. After completion, the reaction was cooled with ice, acidified with 2 M HCl until the pH was 1, and extracted with (3 x 500 mL) diethyl ether. Additionally, the acidic aqueous layer was saturated with sodium chloride and re-extracted with (3 x 500 mL) diethyl ether. The combined organic layers were washed with saturated sodium chloride (3 x 500 mL) and dried over MgSO4. The total combined organic layers were filtered, and evaporated to get the title compound without further purification as a clear oil, (139.2 g, 66% yield). 1H NMR (500 MHz): 1.13 (s, 6H), 2.13 (s, 3H), 2.73 (s, 2H), 9.57 (s, 1H). 13C NMR (133 MHz): 15.40, 22.36, 30.68, 51.63, 65.98, 205.04. |
60% | With oxygen; copper(l) chloride; palladium dichloride In water; N,N-dimethyl-formamide at 20℃; for 72h; Inert atmosphere; Schlenk technique; |
1.4 g | With N,N-diethylpivalamide; oxygen In <i>tert</i>-butyl alcohol for 8h; | |
With oxygen; copper(l) chloride; palladium dichloride In water; N,N-dimethyl-formamide for 72h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With bromine In dichloromethane at 0℃; for 0.5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With carbon monoxide In 1,2-dimethoxyethane at 150℃; for 24h; Yield given. Yields of byproduct given. Title compound not separated from byproducts; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With boron trifluoride diethyl etherate; mercury(II) oxide In tetrahydrofuran; water |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With toluene-4-sulfonic acid In benzene Heating; | |
95% | In benzene for 0.666667h; Heating; | |
95% | With toluene-4-sulfonic acid |
81% | With hydrogen cation | |
76% | With pyridinium p-toluenesulfonate In benzene for 6h; Heating; | |
75% | With toluene-4-sulfonic acid In benzene for 2h; Heating; | |
55% | With pyridinium p-toluenesulfonate In benzene Dean-Stark; Reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
30% | With potassium hydride In N,N,N,N,N,N-hexamethylphosphoric triamide; diethyl ether | |
28% | With potassium hydroxide In 1,2-dimethoxyethane for 4h; | |
With potassium <i>tert</i>-butylate In dichloromethane at 20℃; for 2h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | Stage #1: 1-ethoxyacetylene With n-butyllithium In tetrahydrofuran; hexane; n-heptane at -78℃; for 0.0833333h; Stage #2: 2,2-dimethyl-4-pentenal In tetrahydrofuran; hexane; n-heptane at 26℃; for 0.166667h; | |
With n-butyllithium 1.) THF, hexane, -78 deg C, 2.) THF, hexane, 1.5 h; Yield given. Multistep reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With magnesium sulfate In dichloromethane at 20℃; | ||
In methanol at 20℃; for 5h; | 4.2.2. Preparation of N-benzyl-2,2-diphenyl-4-pentenylamine (1a) General procedure: A solution of 1m (1.19 g, 5 mmol) and benzaldehyde (0.54 g, 5.1 mmol) in MeOH (20 mL) was stirred at room temperature for 5 h, then treated with NaBH4 (0.29 g, 7.5 mmol) and the mixture was stirred overnight. The resulting mixture was treated with water (50 mL), 1 M NaOH (20 mL) and was extracted with CH2Cl2 (100 mL x 3). The combined organic layer was dried (MgSO4) and concentrated. The resulting oily residue was chromatographed (petroleum ether/dichloromethane=3:1) to give 1a (1.32 g, 81%) as a viscous oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With lithium hexamethyldisilazane In tetrahydrofuran at -40℃; | |
85% | With lithium hexamethyldisilazane In tetrahydrofuran at -40℃; | |
85% | With lithium hexamethyldisilazane In tetrahydrofuran at -40℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With 2,2'-biquinoline In tetrahydrofuran; hexane | ||
Stage #1: n-butyllithium; 2,2-dimethyl-4-pentenal In tetrahydrofuran; hexane at -65 - -5℃; for 2h; Cooling with acetone-dry ice; Stage #2: With ammonium chloride In tetrahydrofuran; hexane; water at -60℃; | 1.3 15 g (133 mmol) of 2,2-dimethyl-4-pentenal was added to 600 mL of THF in a 2 L, 3-neck flask, flushed with N2, and sealed with rubber stoppers. The reaction mixture was cooled to -60° C. in a dry ice/acetone bath. Butyllithium solution (2.5 M in hexane, 64.4 mL, 160.7 mmol) was added 4-5 mL at a time from a 20 mL glass syringe. The reaction temperature was kept at -65° C., during addition and afterwards was stirred for an additional hour. The reaction mixture was allowed to warm to -5° C. over 1 hour, cooled to -60° C. again, and slowly quenched with ammonium chloride solution (10.5 g/200 mL water, 200 mmol). THF was evaporated using a rotary evaporator, keeping the water bath temperature set at 30° C. The resultant aqueous solution was first extracted with CH2Cl2 (3×200 mL), and then with ether (1×200 mL). The organic extracts were combined, dried, and concentrated on a rotary evaporator (30° C. water bath) to yield 22.64 g of 4,4-dimethyl-non-1-en-5-ol, TLC Rf=0.67 (1:1 ethyl acetate:hexanes, visualization by 12). 1H NMR (CDCl3, 500 MHz) δ (ppm): 5.86 (m, 1H), 5.06 (m, 1H)), 5.03 (s, 1H), 3.26 (d, 1H), 2.15 (m, 1H), 1.95 (m, 1H), 1.5 (m, 2H), 1.3 (m, 4H), 0.95, (t, 3H), 0.90 (s, 3H), 0.89 (s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With hydroxylamine hydrochloride; sodium carbonate In methanol; water for 24h; | To a solution of 2,2-dimethylpent-4-enal (2.05 mL, 15mmol, 1.0 equiv) in MeOH (50 mL) and H2O (6 mL) was added Na2CO3 (1.91 g, 18 mmol, 1.2equiv) and hydroxylamine hydrochloride (1.25 g, 18 mmol, 1.2 equiv). The reaction mixture wasallowed to stir for 24 h and then was quenched by the addition of H2O (50 mL). The resultingreaction mixture was extracted with Et2O (3 × 50 mL). The Et2O layers were combined, washedwith brine (2 × 50 mL), dried over Na2SO4, and filtered. The filtrate was concentrated in vacuo ,providing 2,2-dimethylpent-4-enal oxime as a clear liquid (1.88 g, 99%). |
90% | With sodium hydroxide; hydroxylamine hydrochloride In ethanol; water | |
84% | With hydroxylamine hydrochloride; sodium hydroxide In ethanol; water |
83% | With hydroxylamine hydrochloride; sodium acetate In water; acetonitrile at 20℃; for 3h; | |
With hydroxylamine hydrochloride; sodium methylate In methanol for 14h; Inert atmosphere; Reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With diisobutylaluminium hydride In pentane at -78 - 20℃; for 3h; | |
Stage #1: 2,2-dimethylpent-4-enenitrile With diisobutylaluminium hydride In pentane at -78 - 20℃; for 8.5h; Inert atmosphere; Stage #2: With hydrogenchloride; sulfuric acid; water; ammonium chloride In formic acid ethyl ester; pentane at 20℃; Inert atmosphere; | ||
With diisobutylaluminium hydride In tetrahydrofuran; hexane at -78 - 23℃; for 2.25h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | With NaH; In tetrahydrofuran; water; pentane; | EXAMPLE 8 Synthesis of 3,3-Dimethyl-5-hexene-1,2-epoxide In a dry box, 2.4 g NaH (0.1 mol) was suspended in 75 mL anhydrous THF. To this stirring mixture was added 12.8 g (0.1 mol) <strong>[5034-06-0]trimethylsulfoxonium chloride</strong>. The mixture was brought to gentle reflux for 2 h. Temperature was then lowered to 55° C. and 10 g 2,2-dimethyl-4-pentenal in 50 mL THF was added slowly. The addition lasted ca. 1.5 h. When addition was complete, the solution was stirred at 55° C. for another h, then overnight at RT. The volume of the solvent was reduced by half. The flask was then taken out of the dry box. Water and pentane were added to extract product. The pentane layer was washed twice with water and dried with anhydrous Na2SO4. Evaporation of pentane gave a liquid that was nearly colorless. The product was allowed to pass through a short silica column by eluding with hexane/ethyl acetate(30:1). Pure product was obtained upon evaporation of the solvents. Yield 67percent. 1H NMR(CDCl3): delta 0.96 (s, 3H, -CH3); 0.99 (s, 3H, -CH3); 2.18 (m, 2H, CH2=CH-CH2-); 2.73 (m, 2H, -CH2-O-); 2.88 (m, 1H, -CH-O-); 5.15 (m, 2H, CH2=CH-); 5.95 (m, 1H, CH2=CH-). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | With oxalyl dichloride; dimethyl sulfoxide; triethylamine In dichloromethane at -78℃; for 0.5h; | |
With sulfur trioxide pyridine complex; dimethyl sulfoxide; triethylamine In dichloromethane at 0℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
52% | Stage #1: 2,2-dimethyl-4-pentenal; cyclohexylamine In methanol at 20℃; for 3h; Stage #2: With sodium tetrahydroborate In methanol for 19h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | Stage #1: 2-((2-(methoxy)ethoxy)methoxy)-1,1,1-trifluoroethane With lithium diisopropyl amide In tetrahydrofuran; hexane at -78℃; for 2h; Stage #2: 2,2-dimethyl-4-pentenal In tetrahydrofuran; hexane at -78 - -30℃; for 2h; | |
61% | Stage #1: 2-((2-(methoxy)ethoxy)methoxy)-1,1,1-trifluoroethane With n-butyllithium; diisopropylamine In tetrahydrofuran; hexane at -78℃; for 0.5h; Stage #2: 2,2-dimethyl-4-pentenal In tetrahydrofuran; hexane at -78 - 20℃; for 18h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | Stage #1: 2,2-dimethyl-4-pentenal; diethylzinc With (1R,2S)-(+)-1-cyclohexyl-2-phenyl-2-(N-morpholino)ethanol In hexane; toluene at 20℃; for 24h; Stage #2: acetic anhydride In hexane; toluene Further stages.; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 86 percent / LiOH / tetrahydrofuran / 48 h / Heating 2: 95 percent / DIBAH / tetrahydrofuran / 2 h / -78 °C | ||
Multi-step reaction with 2 steps 1: 85 percent / LiHMDS / tetrahydrofuran / -40 °C 2: 98 percent / DIBALH / diethyl ether / 0.5 h / 0 °C | ||
Multi-step reaction with 2 steps 1: 85 percent / LiHMDS / tetrahydrofuran / -40 °C 2: 97 percent / DIBALH / diethyl ether / 0.5 h / 0 °C |
Multi-step reaction with 2 steps 1: 85 percent / LiHMDS / tetrahydrofuran / -40 °C 2: 98 percent / DIBALH / diethyl ether / 0.5 h / 0 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With hydroxylamine hydrochloride; 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine In ethyl acetate; N,N-dimethyl-formamide at 100℃; | |
Multi-step reaction with 2 steps 1: Na2SO4 / CH2Cl2 / 10 h / Heating 2: 64 percent / methyl chloroformate / diethyl ether / 1 h / Ambient temperature | ||
With hydroxylamine hydrochloride In 1-methyl-pyrrolidin-2-one at 90℃; | 1-6.a (a) Preparation of Functionalized Olefin reactants; Using the procedures described by Brannock in the Journal of the AmericanChemical Society, vol 81 (1959) pp 3379 to 3383, the following olefin reactants wereprepared: 2,2-dimethyl-4-pentenal; and 2-allyl-2-ethyl-4-pentenal.A portion of the 2,2-dimethyl-4-pentanal was converted to the corresponding 2,2-dimethyl-4-pentenonitrile by placing into a reaction vessel 11.2 g of the aldehyde, 6.9 g ofhydroxylamine hydrochloride (99% purity, Aldrich), and 75 ml of N-methylpyrrolidone(99% purity, Aldrich: M-PYROL), and heating, with stirring, to a temperature of about 90°C to initiate a reaction. The reaction mixture was left stirring until the exotherm subsided,then the contents were poured into a 10 fold volume of water. The organic layer wasseparated and the nitrile was isolated by fractional distillation, collecting the fractionsdistilling at a temperature from about 146 C to about 148 C.2,2-dimethyl-4-allyloxybutenal was prepared from allyl alcohol and ethylenebromide by published methods. The resulting allyl intermediate was reacted withisobutraldehyde in accordance with published methods (Subramanian et al., Chemistry andIndustry, Vol. 16 (1978) page 731) to yield the allyloxyaldehyde. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 12 steps 1: 2) THF, reflux, 20 h 2: PhCH2N(1+)Et3*Cl(1-), KF*2H2O / tetrahydrofuran / 2 h / Heating 3: 87 percent / 1.) n-BuLi / -70 - 20 °C 4: 50 percent / heptane / 20 h / 110 °C 5: 92 percent / hydrogen / Pd/C 6: 79 percent 7: 64 percent / Wacker oxidation 8: 74 percent / KO-t-Bu / 2-methyl-propan-2-ol / 0.5 h / 20 °C 9: KO-t-Bu / 1,2-dimethoxy-ethane / 2 h / 20 °C 10: MCPBA / CH2Cl2 / 1 h 11: DBU / CH2Cl2 12: 74 percent / pyridine, polyhydrogenfluoride | ||
Multi-step reaction with 12 steps 1: 86 percent / n-BuLi / tetrahydrofuran / 1.) -70 deg C, 1 h; 2.) reflux, 20 h 2: 90 percent / benzyltriethylammonium chloride, KF*2H2O / tetrahydrofuran / 3 h / Heating 3: 98 percent / n-BuLi / tetrahydrofuran / -70 - 20 °C 4: 50 percent / heptane / 20 h / 110 °C 5: 92 percent / H2 / Pd-C / ethanol / 20 h / 20 °C 6: 79 percent / NaH / 1,2-dimethoxy-ethane / 0.5 h / 70 °C 7: 64 percent / O2, CuCl / PdCl2 / dimethylformamide; H2O / 24 h / 20 °C 8: 74 percent / t-BuOK / 2-methyl-propan-2-ol / 0.17 h / 20 °C 9: 74 percent / t-BuOK / 2-methyl-propan-2-ol; 1,2-dimethoxy-ethane / 2 h / 20 °C 10: MCPBA / CH2Cl2 / 1 h / 20 °C 11: DBU / CH2Cl2 / 0.25 h / 20 °C 12: 74 percent / pyridinium polyhydrogen fluoride / tetrahydrofuran / 8 h / 60 °C | ||
Multi-step reaction with 12 steps 1: 86 percent / n-BuLi / tetrahydrofuran / 1.) -70 deg C, 1 h; 2.) reflux, 20 h 2: 90 percent / benzyltriethylammonium chloride, KF*2H2O / tetrahydrofuran / 3 h / Heating 3: 98 percent / n-BuLi / tetrahydrofuran / -70 - 20 °C 4: 50 percent / heptane / 20 h / 110 °C 5: 92 percent / H2 / Pd-C / ethanol / 20 h / 20 °C 6: 79 percent / NaH / 1,2-dimethoxy-ethane / 0.5 h / 70 °C 7: 64 percent / O2, CuCl / PdCl2 / dimethylformamide; H2O / 24 h / 20 °C 8: 74 percent / t-BuOK / 2-methyl-propan-2-ol / 0.17 h / 20 °C 9: 74 percent / t-BuOK / 2-methyl-propan-2-ol; 1,2-dimethoxy-ethane / 2 h / 20 °C 10: MCPBA / CH2Cl2 / 1 h / 20 °C 11: DBU / CH2Cl2 / 0.25 h / 20 °C 12: aq. HBF4 / tetrahydrofuran |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 6 steps 1: 2) THF, reflux, 20 h 2: 79 percent / heptane / 110 °C 3: 90 percent / hydrogen / Pd/C 4: 87 percent / HBF4, H2O / tetrahydrofuran 5: 92 percent 6: 67 percent / oxalyl chloride, Me2SO | ||
Multi-step reaction with 6 steps 1: 86 percent / n-BuLi / tetrahydrofuran / 1.) -70 deg C, 1 h; 2.) reflux, 20 h 2: 79 percent / heptane / 20 h / 110 °C 3: 89 percent / H2 / Pd-C / ethanol / 20 °C 4: 87 percent / 25percent aq. HBF4 / tetrahydrofuran / 4 h / 20 °C 5: 92 percent / TsOH*H2O / benzene / 3 h / Heating 6: 67 percent / oxalylchloride, DMSO / CH2Cl2 / 0.5 h / -50 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 5 steps 1: 2) THF, reflux, 20 h 2: PhCH2N(1+)Et3*Cl(1-), KF*2H2O / tetrahydrofuran / 2 h / Heating 3: 87 percent / 1.) n-BuLi / -70 - 20 °C 4: 50 percent / heptane / 20 h / 110 °C 5: 92 percent / hydrogen / Pd/C | ||
Multi-step reaction with 5 steps 1: 86 percent / n-BuLi / tetrahydrofuran / 1.) -70 deg C, 1 h; 2.) reflux, 20 h 2: 90 percent / benzyltriethylammonium chloride, KF*2H2O / tetrahydrofuran / 3 h / Heating 3: 98 percent / n-BuLi / tetrahydrofuran / -70 - 20 °C 4: 50 percent / heptane / 20 h / 110 °C 5: 92 percent / H2 / Pd-C / ethanol / 20 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 6 steps 1: 2) THF, reflux, 20 h 2: PhCH2N(1+)Et3*Cl(1-), KF*2H2O / tetrahydrofuran / 2 h / Heating 3: 87 percent / 1.) n-BuLi / -70 - 20 °C 4: 50 percent / heptane / 20 h / 110 °C 5: 92 percent / hydrogen / Pd/C 6: 79 percent | ||
Multi-step reaction with 6 steps 1: 86 percent / n-BuLi / tetrahydrofuran / 1.) -70 deg C, 1 h; 2.) reflux, 20 h 2: 90 percent / benzyltriethylammonium chloride, KF*2H2O / tetrahydrofuran / 3 h / Heating 3: 98 percent / n-BuLi / tetrahydrofuran / -70 - 20 °C 4: 50 percent / heptane / 20 h / 110 °C 5: 92 percent / H2 / Pd-C / ethanol / 20 h / 20 °C 6: 79 percent / NaH / 1,2-dimethoxy-ethane / 0.5 h / 70 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 8 steps 1: 2) THF, reflux, 20 h 2: PhCH2N(1+)Et3*Cl(1-), KF*2H2O / tetrahydrofuran / 2 h / Heating 3: 87 percent / 1.) n-BuLi / -70 - 20 °C 4: 50 percent / heptane / 20 h / 110 °C 5: 92 percent / hydrogen / Pd/C 6: 79 percent 7: 64 percent / Wacker oxidation 8: 74 percent / KO-t-Bu / 2-methyl-propan-2-ol / 0.5 h / 20 °C | ||
Multi-step reaction with 8 steps 1: 86 percent / n-BuLi / tetrahydrofuran / 1.) -70 deg C, 1 h; 2.) reflux, 20 h 2: 90 percent / benzyltriethylammonium chloride, KF*2H2O / tetrahydrofuran / 3 h / Heating 3: 98 percent / n-BuLi / tetrahydrofuran / -70 - 20 °C 4: 50 percent / heptane / 20 h / 110 °C 5: 92 percent / H2 / Pd-C / ethanol / 20 h / 20 °C 6: 79 percent / NaH / 1,2-dimethoxy-ethane / 0.5 h / 70 °C 7: 64 percent / O2, CuCl / PdCl2 / dimethylformamide; H2O / 24 h / 20 °C 8: 74 percent / t-BuOK / 2-methyl-propan-2-ol / 0.17 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 7 steps 1: 2) THF, reflux, 20 h 2: PhCH2N(1+)Et3*Cl(1-), KF*2H2O / tetrahydrofuran / 2 h / Heating 3: 87 percent / 1.) n-BuLi / -70 - 20 °C 4: 50 percent / heptane / 20 h / 110 °C 5: 92 percent / hydrogen / Pd/C 6: 79 percent 7: 64 percent / Wacker oxidation | ||
Multi-step reaction with 7 steps 1: 86 percent / n-BuLi / tetrahydrofuran / 1.) -70 deg C, 1 h; 2.) reflux, 20 h 2: 90 percent / benzyltriethylammonium chloride, KF*2H2O / tetrahydrofuran / 3 h / Heating 3: 98 percent / n-BuLi / tetrahydrofuran / -70 - 20 °C 4: 50 percent / heptane / 20 h / 110 °C 5: 92 percent / H2 / Pd-C / ethanol / 20 h / 20 °C 6: 79 percent / NaH / 1,2-dimethoxy-ethane / 0.5 h / 70 °C 7: 64 percent / O2, CuCl / PdCl2 / dimethylformamide; H2O / 24 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 9 steps 1: 2) THF, reflux, 20 h 2: PhCH2N(1+)Et3*Cl(1-), KF*2H2O / tetrahydrofuran / 2 h / Heating 3: 87 percent / 1.) n-BuLi / -70 - 20 °C 4: 50 percent / heptane / 20 h / 110 °C 5: 92 percent / hydrogen / Pd/C 6: 79 percent 7: 64 percent / Wacker oxidation 8: 74 percent / KO-t-Bu / 2-methyl-propan-2-ol / 0.5 h / 20 °C 9: KO-t-Bu / 1,2-dimethoxy-ethane / 2 h / 20 °C | ||
Multi-step reaction with 9 steps 1: 86 percent / n-BuLi / tetrahydrofuran / 1.) -70 deg C, 1 h; 2.) reflux, 20 h 2: 90 percent / benzyltriethylammonium chloride, KF*2H2O / tetrahydrofuran / 3 h / Heating 3: 98 percent / n-BuLi / tetrahydrofuran / -70 - 20 °C 4: 50 percent / heptane / 20 h / 110 °C 5: 92 percent / H2 / Pd-C / ethanol / 20 h / 20 °C 6: 79 percent / NaH / 1,2-dimethoxy-ethane / 0.5 h / 70 °C 7: 64 percent / O2, CuCl / PdCl2 / dimethylformamide; H2O / 24 h / 20 °C 8: 74 percent / t-BuOK / 2-methyl-propan-2-ol / 0.17 h / 20 °C 9: 74 percent / t-BuOK / 2-methyl-propan-2-ol; 1,2-dimethoxy-ethane / 2 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 11 steps 1: 2) THF, reflux, 20 h 2: PhCH2N(1+)Et3*Cl(1-), KF*2H2O / tetrahydrofuran / 2 h / Heating 3: 87 percent / 1.) n-BuLi / -70 - 20 °C 4: 50 percent / heptane / 20 h / 110 °C 5: 92 percent / hydrogen / Pd/C 6: 79 percent 7: 64 percent / Wacker oxidation 8: 74 percent / KO-t-Bu / 2-methyl-propan-2-ol / 0.5 h / 20 °C 9: KO-t-Bu / 1,2-dimethoxy-ethane / 2 h / 20 °C 10: MCPBA / CH2Cl2 / 1 h 11: DBU / CH2Cl2 | ||
Multi-step reaction with 11 steps 1: 86 percent / n-BuLi / tetrahydrofuran / 1.) -70 deg C, 1 h; 2.) reflux, 20 h 2: 90 percent / benzyltriethylammonium chloride, KF*2H2O / tetrahydrofuran / 3 h / Heating 3: 98 percent / n-BuLi / tetrahydrofuran / -70 - 20 °C 4: 50 percent / heptane / 20 h / 110 °C 5: 92 percent / H2 / Pd-C / ethanol / 20 h / 20 °C 6: 79 percent / NaH / 1,2-dimethoxy-ethane / 0.5 h / 70 °C 7: 64 percent / O2, CuCl / PdCl2 / dimethylformamide; H2O / 24 h / 20 °C 8: 74 percent / t-BuOK / 2-methyl-propan-2-ol / 0.17 h / 20 °C 9: 74 percent / t-BuOK / 2-methyl-propan-2-ol; 1,2-dimethoxy-ethane / 2 h / 20 °C 10: MCPBA / CH2Cl2 / 1 h / 20 °C 11: DBU / CH2Cl2 / 0.25 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1: 2) THF, reflux, 20 h 2: 79 percent / heptane / 110 °C 3: 90 percent / hydrogen / Pd/C 4: 87 percent / HBF4, H2O / tetrahydrofuran | ||
Multi-step reaction with 4 steps 1: 86 percent / n-BuLi / tetrahydrofuran / 1.) -70 deg C, 1 h; 2.) reflux, 20 h 2: 79 percent / heptane / 20 h / 110 °C 3: 89 percent / H2 / Pd-C / ethanol / 20 °C 4: 87 percent / 25percent aq. HBF4 / tetrahydrofuran / 4 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 7 steps 1: 2) THF, reflux, 20 h 2: 79 percent / heptane / 110 °C 3: 90 percent / hydrogen / Pd/C 4: 87 percent / HBF4, H2O / tetrahydrofuran 5: 92 percent 6: 67 percent / oxalyl chloride, Me2SO 7: Li/NH3 / further reducing agents | ||
Multi-step reaction with 7 steps 1: 86 percent / n-BuLi / tetrahydrofuran / 1.) -70 deg C, 1 h; 2.) reflux, 20 h 2: 79 percent / heptane / 20 h / 110 °C 3: 89 percent / H2 / Pd-C / ethanol / 20 °C 4: 87 percent / 25percent aq. HBF4 / tetrahydrofuran / 4 h / 20 °C 5: 92 percent / TsOH*H2O / benzene / 3 h / Heating 6: 67 percent / oxalylchloride, DMSO / CH2Cl2 / 0.5 h / -50 °C 7: Li, NH3 / tetrahydrofuran |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 5 steps 1: 2) THF, reflux, 20 h 2: 79 percent / heptane / 110 °C 3: 90 percent / hydrogen / Pd/C 4: 87 percent / HBF4, H2O / tetrahydrofuran 5: 92 percent | ||
Multi-step reaction with 5 steps 1: 86 percent / n-BuLi / tetrahydrofuran / 1.) -70 deg C, 1 h; 2.) reflux, 20 h 2: 79 percent / heptane / 20 h / 110 °C 3: 89 percent / H2 / Pd-C / ethanol / 20 °C 4: 87 percent / 25percent aq. HBF4 / tetrahydrofuran / 4 h / 20 °C 5: 92 percent / TsOH*H2O / benzene / 3 h / Heating |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: 2) THF, reflux, 20 h 2: 79 percent / heptane / 110 °C 3: 90 percent / hydrogen / Pd/C | ||
Multi-step reaction with 3 steps 1: 86 percent / n-BuLi / tetrahydrofuran / 1.) -70 deg C, 1 h; 2.) reflux, 20 h 2: 79 percent / heptane / 20 h / 110 °C 3: 89 percent / H2 / Pd-C / ethanol / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | Stage #1: 2,2-dimethyl-4-pentenal; diethylzinc In toluene at 20℃; for 72h; Stage #2: With acetic anhydride for 48h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With piperidine; acetic acid In toluene for 18h; Heating / reflux; | 5 2-Cyano-4,4-dimethyl-hepta-2,6-dienoic acid ethyl ester. A solution of 2,2-dimethyl-pent-4-enal (5.0 g, 44 mmol), cyano-acetic acid ethyl ester (5.12 mL, 48 mmol), piperidine (1.3 mL, 14 mmol) and acetic acid (4.52 mL, 80 mmol) in 170 mL of toluene was heated under reflux for 18 hours in a flask equipped with a Dean-Stark separator. Several mL of water was collected in the trap. The reaction was cooled and washed with 1N HCl, NaHCO3 and brine, successively. The organic layers were dried over Na2SO4 and concentrated to an oil. This oil was chromatographed eluting with 20% of EtOAc in hexane to give a combination of two lots total 8.3 g (91%). 1H NMR (400 MHz; CDCl3) 1.28 (s, 6H), 1.32 (t, 3H, J=7 Hz), 2.26 (d, 2H, J=7.6 Hz), 4.27 (q, 2H, J=7.2 Hz), 5.08 (d, 1H, J=12 Hz), 5.10 (d, 1H, J=4 Hz), 5.72 (m, 1H) |
91% | With piperidine; acetic acid In toluene for 18h; Heating / reflux; | 5 2-Cyano-4, 4-dimethyl-hepta-2, 6-dienoic acid ethyl ester. A solution of 2, 2-dimethyl-pent-4-enal (5. 0g, 44 mmol), cyano-acetic acid ethyl ester (5.12 mL, 48 MMOL), piperidine (1.3 mL, 14 MMOL) and acetic acid (4.52 mL, 80 MMOL) in 170 mL of toluene was heated under reflux for 18 hours in a flask equipped with a Dean-Stark separator. Several mL of water was collected in the trap. The reaction was cooled and washed with 1 N HCI, NAHCO3 and brine, successively. The organic layers were dried over NA2SO4 and concentrated to an oil. This oil was chromatographed eluting with 20% of EtOAc in hexane to give a combination of two lots total 8.3g (91%).H NMR (400 MHz; CECI3) 1.28 (s, 6H), 1.32 (t, 3H, J = 7 Hz),. 2.26 (d, 2H, J = 7. 6 Hz), 4.27 (q, 2H, J = 7.2 Hz), 5.08 (d, 1 H, J = 12 Hz), 5.10 (d, 1H, J= 4 HZ), 5.72 (m, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With trichlorosilane In isopropyl alcohol at 100 - 120℃; | 1.b Examples 1-6:; The Example process is carried out by placing an aliquot of the selectedfunctionalized olefin reactant into a reaction flask equipped with an external heat source, areflux condenser, a stirring apparatus, and a dropping funnel. The reaction flask thuscharged is purged with nitrogen to maintain an inert atmosphere and the dropping funnelcharged with the selected silicon reactant. The reaction is maintained under an inertatmosphere and 0.025 mole of chloroplatinic acid is added to the olefin reactant as a 0.1 Msolution in isopropanol. The reaction flask is heated initially to about 110 °C. After theinitial temperature is reached, the silicon reactant is added dropwise with continued stirring.The reaction temperature is maintained at a temperature from about 100 °C to about 120 °Ceither by continued heating or by adjusting the rate of addition of the silicon reagent, or acombination of the two. After all of the silicon reactant has been added the reactiontemperature is maintained by continued heating with stirring for three additional hours. Atthe end of the reaction period, reaction completion is verified by assaying the reactionmixture for residual functionalized olefin reactant and for carbo-silicon product by gaschromatographic analysis (GC) using published methods. In some reactions, additionalheating to temperatures as high as 170° C were performed to increase the initial yield orconversion.In all cases, the product formed was isolated by fractional distillation, at reducedpressure as needed, and the isolated product was analyzed by published infraredspectroscopic methods to verify the product formed in the reaction.In addition to the reactants prepared as described below, trichlorosilane (99%purity), dimethylchlorosilane (99% purity), and tetramemyldisiloxane 97% purity (siliconreactants) were obtained from Aldrich used as received. All other reagents were ACSgrade reagent articles of commerce obtained from commercial sources.; (b) Preparation of the Carbo-silanesCarbo-silanes of the invention were prepared using the inventive process by reactingthe functionalized olefin reactant indicated in rows 1 through 3 of Table II, below, with theindicated silane silicon reactant to yield the indicated product by the above-describedprocedure.Carbo-siloxanes were prepared using the inventive process by reacting thefunctionalized olefm reactant indicated in rows 4 of Table II with the indicated siloxanesilicon reactant to yield the indicated product. The product of Example 4 was prepared bythe above-described procedure.In each of the Examples, the mole % conversion of functionalized olefin reactantindicated in the table was determined by GC, as described above.Table IIEx.No.Silicon ReactantFunctionalized Olefm reactantProductYield*1trichlorosilane2,2-dimethyl-4 pentenal2,2-dimethyl-5-trichlorosilyl-pentanal85%2dimethyl-chlorosilane2,2-dimethyl-4 pentenal2,2-dimethyl-5-dimethyl-chlorosilyl-pentanal50%3dimethyl-chlorosilane2,2-dimethyl-4-pentenonitrile1 , 1 -dimethyl-5 -(dimethyl-chlorosilyl)-pentanonitrile75%4tetramethyl-disiloxane2,2-dimethyl-4-pentenonitrilel,2-bis(2,2-dimethyl-4-pentanonitrile)-tetramethyl-disiloxane82%5tetramethyldisiloxane2,2-dimethyl-4pentenal1 ,2-bis(2,2-dimethyl-4-pentanal)-tetramethyldisiloxane50%6trimethoxysilane2,2-dimethy.-4pentenal2,2-dimethyl-5-trimethoxysilylpentanal80%* % base on moles of olefin reactant consumedThese examples demonstrate that the process of the present invention provides afacile, high yield route to direct production of carbo-silicon compounds having mixtures ofsubstiruents, including those which can not be provided by derivative routes and includingthose which have a substantial potential to impede a hydrosilation reaction. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | In benzene | 92.a a. a. Allyl-(2,2-dimethyl-pent-4-enylidene)-amine 2,2-Dimethyl-4-pentenal (2.8 g, 25 mmol) was dissolved in 15 mL benzene. To this solution allylamine (2.85 g, 50 mmol) was added. A few molecular sieves were used to absorb water generated during the reaction. The mixture was stirred at room temperature overnight. Removal of the solvent and excess amount of allylamine on rotavapor provided 3.76 g of the title compound as clear liquid (yield 100%). 1H-NMR (400 MHz, CDCl3):. 7.52(s, 1H), 5.99-5.90(m, 1H), 5.80-5.70(m, 1H), 5.15-4.99(m, 4H), 4.01-3.99(m, 2H), 2.17(d, 2H), 1.06(s, 6H). |
100% | In benzene | 92.a a.) a.) Allyl-(2,2-dimethyl-pent-4-enylidene)-amine 2,2-Dimethyl-4-pentenal (2.8 g, 25 mmol) was dissolved in 15 mL benzene. To this solution allylamine (2.85 g, 50 mmol) was added. A few molecular sieves were used to absorb water generated during the reaction. The mixture was stirred at room temperature overnight. Removal of the solvent and excess amount of allylamine on rotavapor provided 3.76 g of the title compound as clear liquid (yield 100%). 1H-NMR (400 MHz, CDCl3): 7.52(s, 1H), 5.99-5.90(m, 1H), 5.80-5.70(m, 1H), 5.15-4.99(m, 4H), 4.01-3.99(m, 2H), 2.17(d, 2H), 1.06(s, 6H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
40.7% | With n-butyllithium In tetrahydrofuran; hexane; water; toluene | 2 1-(3Chlorophenyl)-3,3-dimethyl-1-(1-imidazolyl)-5-hexen-2-ol EXAMPLE 2 1-(3Chlorophenyl)-3,3-dimethyl-1-(1-imidazolyl)-5-hexen-2-ol 16.2 ml (25.1 mmol) of a 1.55 molar solution of n-butyllithium in hexane were added dropwise to a solution of 4.82 g (25 mmol) of 1-(3-chlorobenzyl)-imidazole in 50 ml of absolute THF at -70° C. The mixture was stirred for a further 30 minutes at -70° C., and a solution of 3.75 g of 75% purity (25 mmol) (containing 15% of toluene) 2,2-dimethyl-4-pentenaldehyde in 38 ml of absolute THF was then added dropwise at about -70° C. over about 15 minutes. The reaction mixture was subsequently stirred for a further 15 minutes at about -70° C. and allowed to warm to room temperature over about 2 hours, 350 ml of water were added at 1°-10° C. with cooling, the mixture was stirred for a further 30 minutes at 10°-20° C., the phases were separated, and the aqueous phase was extracted repeatedly with ether. The combined organic solutions were further worked up as described in Example 1. The extract residue (7.2 g) was chromatographed, eluding with CH2 Cl2 /hexane 1:2 and 1:1 mixtures, CH2 Cl2 and CH2 Cl2 /C2 H5 OH mixtures with an increasing C2 H5 OH content (to a maximum of 2% by volume) on a silica gel S/CH2 Cl2: hexane 1:2 column (φ2.8 cm, height 43 cm). After elution of 0.60 g preliminary fractions, 5.0 g of product, in which the compound desired was greatly concentrated, were eluted. From this proportion, 3.10 g (≅40.7% yield) of pure 1-(3-chlorophenyl)-3,3-dimethyl1-(1-imidazolyl)-5-hexen-2-ol of melting point 95° C. were obtained by crystallization from diisopropyl ether C17 H21 ClN2 O (304.83) calculated: C 66.98 H 6.94 Cl 11.63 N 9.19% found: C 67.4 H 7.1 Cl 12.0 N 9.2%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
43.6% | With diisopropylamine In tetrahydrofuran; C2 H5 OH; water | 6 1-(3-Bromophenyl)-3,3-dimethyl-1-(1-imidazolyl)-5-hexen-2-ol EXAMPLE 6 1-(3-Bromophenyl)-3,3-dimethyl-1-(1-imidazolyl)-5-hexen-2-ol A solution of lithium diisopropylamide was prepared in 40 ml of absolute tetrahydrofuran (THF) at -30° C. starting from 2.06 g (20.4 mmol) of diisopropylamine and 13.4 ml of 1.5 molar n-butyllithium/hexane solution (20 mmol). A solution of 4.75 g (20 mmol) of 1-(3-bromobenzyl)imidazole in 25 ml of absolute THF was added dropwise to this solution at -70° C. to -78° C., the mixture was stirred at about -70° C. for a further 30 minutes, a solution of 3.22 g of 70% purity (20 mmol) 2,2-dimethyl-4-pentenaldehyde in 30 ml of absolute THF was subsequently added dropwise at about -70° C., and the mixture was stirred at about -70° C. for a further 20 minutes and allowed to warm to room temperature over about 2.5 hours 300 ml of water were subsequently added dropwise at 0° C.-5° C., and the mixture was stirred for 1 hour with ice cooling. After separating the phases, the aqueous solution was extracted repeatedly with ether. The combined organic solutions were further worked up as described in Example 1. The extract residue (7.3 g) was chromatographed by elution with CH2 Cl2 and CH2 Cl2 /C2 H5 OH mixtures with an increase in C2 H5 OH content (to a maximum of 2% by volume) on a silica gel S/CH2 Cl2 column (φ 2.8 cm, height 48 cm). After elution of 2.0 g preliminary fractions, 5.2 g of product were eluted in which the compound desired was greatly concentrated. From these 5.2 g, 3.05 g (φ 43.6% yield) of pure 1-(3-bromophenyl)-3,3-dimethyl-1-(1-imidazolyl)-5-hexen-2-ol of melting point 126° C. were obtained by crystallization from diisopropyl ether/hexane 2:1. C17 H21 BrN2 O (349.29) calculated: C 58.46 H 6.06 Br 22.88 N 8.02% found: C 58.4 H 6.1 Br 23.8 N 8.0%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With aluminum isopropoxide; In water; | To the obtained crude vitamin A, 1.86 g (16.5 mmol) of 2,2-dimethyl-4-pentenal and 86 mg (0.42 mmol) of aluminum isopropoxide were added, and the reaction mixture was agitated at 35-40 C. for 60 min. After the stopping of reaction by the addition of 0.07 ml of water, unreacted 2,2-dimethyl-4-pentenal and 2,2-dimethyl-4-penten-1-ol formed as a reaction by-product were distilled off (at 60 C., 10 mmHg) to obtain 3.77 g of crude vitamin A aldehyde (purity 55.5%, yield 87%, total trans form ratio 98%). The obtained crude vitamin A aldehyde was recrystallized from hexane to obtain 1.25 g of purified vitamin A aldehyde (melting point 60-61 C.). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With acetic anhydride In hexane; toluene | 6 EXAMPLE 6 EXAMPLE 6 To a vial containing aminoalcohol 1 (0.05 g, 0.17 mmol) prepared as in Example 1 was added a solution containing 2,2-dimethyl-4-pentenal (0.34 g, 90% pure, 2.7 mmol), toluene (3.0 mL), and 1 M diethylzinc in hexane (6.0 mL). After 3 days at room temperature, acetic anhydride (1.2 mL, 13 mmol) was added. After 2 additional days, the mixture was diluted in ether (50 mL) and the reaction was quenched by dropwise addition of half-saturated aqueous ammonium chloride (50 mL). The ether layer was separated and the aqueous layer was further extracted with ether (2*50 mL). The combined ether layers were dried over magnesium sulfate whereupon the solvent was removed at reduced pressure. The residue was purified by flash chromatography on 220-400 mesh silica with 95% hexane and 5% ether as eluant. The product (+)-3-acetoxy-4,4-dimethylhept-1-ene (0.39 g, 78%) was isolated as a colorless liquid by distillation of the solvent at reduced pressure. Anal. for C11H20O2. Calcd: C, 71.70; H, 10.94; found: C, 71.75; H, 10.66. 1H NMR (CDCl3/TMS): δ0.84 (s+t, 6 H total), 0.87 (s, 3 H), 1.46 (m, 1 H), 1.62 (m, 1 H), 1.89-2.06 (m, 2 H), 2.07 (s, 3 H), 4.71 (dd, 1 H), 4.96-5.05 (m, 2 H), 5.81 (m, 1 H). 13C NMR (CDCl3/TMS): δ10.96, 21.02, 22.33, 23.12, 37.41, 43.46, 81.41, 117.37, 134.74, 171.11. [α]D25=+14.2, c=2.02 g/100 mL chloroform. Chiral capillary gas chromatographic analysis at 100° C. on Cyclodex B stationary phase (J & W Scientific) indicated that the enantiomeric excess of the product was 98%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | Stage #1: tert-butyl diethylphosphonoacetate With sodium hydride In tetrahydrofuran for 2h; Stage #2: 2,2-dimethyl-4-pentenal In tetrahydrofuran at 20℃; for 16h; Further stages.; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With sodium hydride In ethanol at 20℃; for 5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
To a freshly prepared tetrahydrofuran (300 mL) solution of lithium diisopropylamide (0.19 mol) under nitrogen at 00C was added dropwise in 30 minutes a tetrahydrofuran (200 mL) solution of diphenyl(methoxymethyl) phosphinoxide (49.5 g, 0.2 mol). After stirring for 15 minutes at 00C, a tetrahydrofuran (100 mL) solution of 2,2-dimethylpent-4-enal (24.5 g, 0.22 mol) was added <n="28"/>dropwise in 20 minutes to the cherry-colored mixture. After 15 minutes, the mixture was warmed to room temperature and then refluxed for 5 hours. The mixture was cooled to room temperature, charged with water (20 mL), and cooled at 00C under vigorous stirring. The resulting solid was filtered, washed with hexanes, and discarded. The filtrates were collected and distilled at 101-102 0C (155 mmHg) to give the title compound as a colorless oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
64% | With sodium acetate In N,N-dimethyl-formamide at 110℃; for 20h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With dihydrogen peroxide; copper(l) chloride In water; <i>tert</i>-butyl alcohol at 20℃; for 28h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | Stage #1: 2,2-dimethyl-4-pentenal; diethylzinc With (1S,2R,3S,5S)-6,6-dimethyl-3-morpholinobicyclo[3.1.1]heptan-2-ol; (1R,2S,3R,5R)-6,6-dimethyl-3-morpholinobicyclo[3.1.1]heptan-2-ol In hexane at -15 - 0℃; for 18h; Inert atmosphere; Stage #2: With water; ammonium chloride In hexane at 0℃; optical yield given as %ee; enantioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | Stage #1: 2,2-dimethyl-4-pentenal; diethylzinc With (1S,2R,3S,5S)-6,6-dimethyl-2-morpholinobicyclo[3.1.1]heptan-3-ol; (1R,2S,3R,5R)-6,6-dimethyl-2-morpholinobicyclo[3.1.1]heptan-3-ol In hexane at -15 - 0℃; for 18h; Inert atmosphere; Stage #2: With water; ammonium chloride In hexane at 0℃; optical yield given as %ee; enantioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With acetic acid In methanol Reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | Stage #1: 4-[1-ethyl-1-(4-ethynyl-3-methylphenyl)-propyl]-2-methylphenol With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 1h; Stage #2: 2,2-dimethyl-4-pentenal In tetrahydrofuran; hexane at -78 - 20℃; for 12h; Stage #3: With ammonium chloride In tetrahydrofuran; hexane; water | 38.1 To a solution of 4- [l-ethyl-I- (4-ethynyl-3-methyl-phenyl)-propyl]-2-methyl- phenol (compound prepared in Example 1- (3)) (1 g, 3.42 mmol) in THF (20 ml) was added 1.6N n-BuLi in Hex (5.34 ml, 8. 55 mmol) at-78 degrees C under nitrogen atmosphere. The mixture was stirred at-78 degrees C for 1 h and 2, 2-dimethyl-4-pentenal (1.39 mi, 10.26 mmol) was added. The reaction mixture was warmed to room temperature and stirred for 12 h. The mixture was poured into saturated NH4CI aq. and the products were extracted with EtOAc. The extracts were washed with brine, dried over MgS04, filtered and concentrated under reduced pressure. The obtained residue was purified by Silica gel chromatography (EtOAc: n-Hexane=1: 12) to give the title compound (829 mg, 60%). 1H-NMR (300MHz, CDCl3) : 0.59 (t, 6H), 1.04 (d, 6H), 2.03 (q, 4H), 2.18 (s, 3H), 2.20 (m, 2H), 2.38 (s, 3H), 4.34 (s, 1H), 5.10 (m, 2H), 5.87 (m, 1H), 6.65 (d, 1 H), 6.80-7. 00 (m, 4H), 7.28 (d, 1 H) ; MS (ESI-) : 403 ([M-H]-). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | Stage #1: 1,1-dibromo-1,3-pentadiene With n-butyllithium In tetrahydrofuran at -78 - 20℃; Inert atmosphere; Stage #2: 2,2-dimethyl-4-pentenal In tetrahydrofuran at -78℃; for 0.583333h; Inert atmosphere; Stage #3: methyl chloroformate In tetrahydrofuran at -78℃; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | With C36H28Br2Sn; sodium methylate In methanol; toluene at 20℃; for 19h; Inert atmosphere; optical yield given as %ee; enantioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With C36H28Br2Sn; sodium methylate In methanol; toluene at 20℃; for 19h; Inert atmosphere; optical yield given as %ee; enantioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | Stage #1: Cyclopropylacetylene With (1R,2R)-3-tert-butyldimethylsilyloxy-2-(N,N-dimethylamino)-1-p-nitrophenyl-1-propanol; zinc trifluoromethanesulfonate; triethylamine In toluene at 55℃; for 0.5h; Inert atmosphere; Stage #2: 2,2-dimethyl-4-pentenal In toluene at 55℃; for 46h; Inert atmosphere; optical yield given as %ee; enantioselective reaction; | |
90% | Stage #1: Cyclopropylacetylene With (1R,2R)-3-tert-butyldimethylsilyloxy-2-(N,N-dimethylamino)-1-p-nitrophenyl-1-propanol; zinc trifluoromethanesulfonate; triethylamine In toluene at 55℃; for 0.5h; Inert atmosphere; Stage #2: 2,2-dimethyl-4-pentenal In toluene at 55℃; for 46h; Inert atmosphere; optical yield given as %ee; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With ethanol; sodium hydride In mineral oil at 20℃; for 5h; Inert atmosphere; | 6.4.24. 4,4-Dimethyl-1-phenyl-hepta-2,6-dien-1-one Sodium hydride (60% in mineral oil, 800 mg, 20 mmol) was added to 60 mL of ethanol and stirred at room temperature for 15 min. This was followed by the addition of acetophenone (2.4 g, 20 mmol) and 2,2-dimethyl-4-pentenal (2.5 g, 20 mmol). The reaction mixture then was allowed to stir at room temperature for 5 h. Upon completion of the aldol reaction, the ethanol was removed in vacuo. The crude mixture was diluted with ethyl acetate, washed with water, dried over MgSO4, and filtered through a short pad of Celite. Purification by column chromatography using 6% ethyl acetate in hexanes provided 3.5 g (81%) of 4,4-dimethyl-1-phenyl-hepta-2,6-dien-1-one as a colorless oil. 1H NMR (CDCl3, 500 MHz): δ 7.90-7.95 (m, 2H, aromatic H), 7.53-7.59 (m, 1H, aromatic H), 7.44-7.50 (m, 2H, aromatic H), 7.02 (d, J=15.7 Hz, 1H), 6.76 (d, J=15.7 Hz, 1H), 5.75 (ddt, J=16.7, 10.2, 7.3 Hz, 1H), 5.07 (dm, J=10.2 Hz, 1H), 5.05 (dm, J=16.7 Hz, 1H), 2.18 (d, J=7.3 Hz, 2H), 1.13 (s, 6H). 13C NMR (CDCl3, 75 MHz): δ 191.1, 158.0, 138.0, 134.2, 132.4, 128.4, 128.3, 122.1, 117.7, 46.4, 37.0, 26.1. IR (NaCl, cm-1): 3075, 3004, 2963, 2928, 2871, 1673, 1651, 1620, 1598, 1580, 1464, 1448, 1385, 1365, 1329, 1298, 1283, 1221, 1180, 1090, 1035, 1019, 993, 916. HRMS (EI+) calcd for C15H18O: 214.13577, Found: 214.13550. Anal. Calcd for C15H18O: C, 84.07; H, 8.47. Found: C, 83.84; H, 8.60. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | Stage #1: butanone With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 0.916667h; Inert atmosphere; Stage #2: 2,2-dimethyl-4-pentenal In tetrahydrofuran at -78℃; for 2h; Inert atmosphere; Stage #3: With water; ammonium chloride In tetrahydrofuran at -78℃; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | Stage #1: 2-bromo-3,3,3-trifluoropropene With n-butyllithium; N-ethyl-N,N-diisopropylamine In tetrahydrofuran; hexane at -78℃; for 0.333333h; Inert atmosphere; Stage #2: 2,2-dimethyl-4-pentenal In tetrahydrofuran; hexane at -78℃; for 1h; Inert atmosphere; | 4.3. Preparation of fluorine-containing propargyl alcohol 7 General procedure: To a solution of diisopropylamine (4.20 mL, 30 mmol) in THF (100 mL) was added 1.6 M n-BuLi solution in hexane (18.75 mL, 30 mmol) at -78 °C and the whole was stirred for 20 min. To this solution was added 2-bromo-3,3,3-trifluoropropene (1.50 mL, 15 mmol) very slowly. After stirring at -78 °C for 20 min, various aldehydes (10 mmol) or ketones (10 mmol) were added to the solution and the whole was stirred for 1 h at -78 °C. The reaction mixture was quenched with saturated NH4Cl aq. and extracted with ethyl acetate three times. The combined organic layers were dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was chromatographed on silica gel to afford fluorine-containing propargyl alcohols 7 and 8. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | Stage #1: (methoxymethyl)triphenylphosphonium chloride With potassium <i>tert</i>-butylate In tetrahydrofuran at 0℃; for 1h; Inert atmosphere; Stage #2: 2,2-dimethyl-4-pentenal In tetrahydrofuran at 0 - 20℃; for 2.5h; Stage #3: With sulfuric acid In tetrahydrofuran; water at 0 - 20℃; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | Stage #1: diethoxyphosphoryl-acetic acid ethyl ester With sodium hydride In tetrahydrofuran; mineral oil at 0℃; for 1h; Inert atmosphere; Stage #2: 2,2-dimethyl-4-pentenal In tetrahydrofuran; mineral oil at 0 - 20℃; for 72h; Inert atmosphere; | 4 To a suspension of sodium hydride (60% in mineral oil, 783 mg, 19.6 mmol) in dry tetrahydrofuran at 0°C, under nitrogen was added dropwise triethyl phosphonoacetate (3.38 ml_, 19.6 mmol). The white suspension was stirred for 1 h where it became a solution, then 2,2- dimethyl-4-pentenal (2.42 ml_, 17.8 mmol) was slowly added and the resulting green/yellow solution was stirred at 0°C and allowed to warm to RT. After 72 h ethanol (1 ml.) was added to the solution, followed by water (100 ml.) and the organics were extracted with diethyl ether (2 x 200 ml_). The combined organics were washed with water (200 ml_), dried over magnesium sulfate, filtered and concentrated in vacuo to give a crude residue. This was purified by silica gel chromatography, using /'so-hexanes (144 ml_), then /'so-hexanes/diethyl ether 50:50 (72 ml_), then diethyl ether (48 ml.) to give the title compound (3.20 g, 99%) as an oil |
99% | Stage #1: diethoxyphosphoryl-acetic acid ethyl ester With sodium hydride In tetrahydrofuran; mineral oil at 0℃; for 1h; Inert atmosphere; Stage #2: 2,2-dimethyl-4-pentenal In tetrahydrofuran; mineral oil at 0 - 20℃; for 72h; | 4 To a suspension of sodium hydride (60% in mineral oil, 783 mg, 19.6 mmol) in dry tetrahydrofuran at 0° C., under nitrogen was added dropwise triethyl phosphonoacetate (3.38 mL, 19.6 mmol). The white suspension was stirred for 1 h where it became a solution, then 2,2-dimethyl-4-pentenal (2.42 mL, 17.8 mmol) was slowly added and the resulting green/yellow solution was stirred at 0° C. and allowed to warm to RT. After 72 h ethanol (1 mL) was added to the solution, followed by water (100 mL) and the organics were extracted with diethyl ether (2×200 mL). The combined organics were washed with water (200 mL), dried over magnesium sulfate, filtered and concentrated in vacuo to give a crude residue. This was purified by silica gel chromatography, using iso-hexanes (144 mL), then iso-hexanes/diethyl ether 50:50 (72 mL), then diethyl ether (48 mL) to give the title compound (3.20 g, 99%) as an oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With 1,4-diaza-bicyclo[2.2.2]octane In neat (no solvent) at 55℃; for 12h; Inert atmosphere; | |
83% | With 1,4-diaza-bicyclo[2.2.2]octane In neat (no solvent) at 55℃; for 12h; | 4.1.1. Aldehydes General procedure: To 1.0 equiv. of phenol were added successively 1.0 equiv. of DABCO, 2.0 equiv. of aldehyde and 1.0 equiv. of isocyanide. The resulting mixture was stirred neat at 55 °C for 12 h. The crude product was purified by flash chromatography on silica gel. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With <i>L</i>-proline In chloroform at 30℃; enantioselective reaction; | General Procedure for the (S)-Proline Catalyzed Aldol Reaction of Acetone with α-Trisubstituted Aliphatic Aldehydes General procedure: (S)-proline (23 mg, 0.20 mmol, 0.20 equiv) was added to a solution of aldehyde (1 mmol, 1 equiv) indry acetone (4 mL) and dry chloroform (1 mL) and was stirred at 30 °C. After this time the mixturewas diluted with water (5 mL) and diethyl ether (5 mL) and partitioned. The aqueous layer was washed with diethyl ether (5 mL x 3), and the combined organic layers were dried over Na2SO4. Evaporation of the solvent and flash column chromatography with the specified solvent system afforded the desired products. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With rac-Pro-OH In chloroform at 30℃; | General Procedure for the (S)-Proline Catalyzed Aldol Reaction of Acetone with α-Trisubstituted Aliphatic Aldehydes General procedure: (S)-proline (23 mg, 0.20 mmol, 0.20 equiv) was added to a solution of aldehyde (1 mmol, 1 equiv) indry acetone (4 mL) and dry chloroform (1 mL) and was stirred at 30 °C. After this time the mixturewas diluted with water (5 mL) and diethyl ether (5 mL) and partitioned. The aqueous layer was washed with diethyl ether (5 mL x 3), and the combined organic layers were dried over Na2SO4. Evaporation of the solvent and flash column chromatography with the specified solvent system afforded the desired products. Racemates All racemates were prepared following the same general procedure for the asymmetric reaction, usingrac-proline as catalyst. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: diethyl 1-chloro-(1-cyanomethyl)phosphonate With lithium hexamethyldisilazane In tetrahydrofuran at -10℃; for 0.25h; Stage #2: 2,2-dimethyl-4-pentenal In tetrahydrofuran at 0℃; for 0.416667h; Overall yield = 84 %; Overall yield = 2.58 g; Optical yield = 46 %de; | 2.1 Preparation of (2Z)-2-chloro-4,4-dimethyl-hepta-2,6-dienenitrile and (2E)-2-chloro-4,4-dimethyl-hepta-2,6-dienenitrile (Step 1) 2-chloro-2-diethoxyphosphoryl-acetonitrile (3.80g, 18. OmM) was dissolved in 15ml dry THF then cooled to -10°C with stirring. Lithium bis(trimethylsilyl)amide (1 M in THF, 18.0ml, 18. OmM) was added dropwise over 15 minutes to give an amber solution then 2,2-dimethylpent-4-enal (2.12g, 18.9mM) was added over 5 minutes and stirred at 0°C. After 20 minutes at 0°C the reaction was diluted with isohexane (200ml) then washed sequentially with 2N HCI (aq, 20ml) , water (20ml), saturated NaHC03(aq, 20ml), water (10ml), saturated brine (aq, 10ml), then passed through phase separation cartridge to remove any droplets of water and evaporated to give an amber oil (2.58g , 84%). H NMR (CDCI3) showed a 73:27 mixture of geometric isomers:- Major isomer 6.53 (s, 1 H), 5.72 (m, 1 H), 5.13 (m, 1 H), 5.09 (m, 1 H), 2.22 (dm, 2H), 1.28 (s, 6H) Minor isomer 6.56 (s, 1 H), 5.72 (m, 1 H), 5.17 (m, 1 H), 5.14 (m, 1 H), 2.27 (dm, 2H), 1.25 (s, 6H) | |
With lithium hexamethyldisilazane In tetrahydrofuran at -10 - 0℃; for 0.666667h; Overall yield = 84 %; Overall yield = 2.58 g; Optical yield = 46 %de; | 1.1 Preparation of (2Z)-2-chloro-4,4-dimethyl-hepta-2,6-dienenitrile and (2E)-2-chloro-4,4- dimethyl-hepta-2,6-dienenitrile 2-chloro-2-diethoxyphosphoryl-acetonitrile (3.80g, 18.0mM) was dissolved in 15m1 dry THE thencooled to -10°C with stirring. Lithium bis(trimethylsilyl)amide (1M in THE, 18.Oml, 18.0mM) was added dropwise over 15 minutes to give an amber solution then 2,2-dimethylpent-4-enal (2.12g, 18.9mM) was added over 5 minutes and stirred at 0°C. After 20 minutes at 0°C the reaction was diluted with isohexane (200m1) then washed sequentially with 2N HCI (aq, 20m1) , water (20m1), saturated NaHCO3(aq, 20m1), water (lOmI), saturated brine (aq, lOmI), then passed throughphase separation cartridge to remove any droplets of water and evaporated to give an amber oil (2.58g , 84%). 1H NMR (CDCI3) showed a 73:27 mixture of geometric isomers:-Major isomer 6.53 (s, 1H), 5.72 (m, 1H), 5.13 (m, 1H), 5.09(m, 1H), 2.22 (dm, 2H), 1.28(s, 6H) Minor isomer 6.56(s, 1H), 5.72 (m, 1H), 5.17 (m, 1H), 5.14(m, 1H), 2.27 (dm, 2H), 1.25(s, 6H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | With sodium tris(acetoxy)borohydride; acetic acid In dichloromethane at 0 - 20℃; for 12h; Inert atmosphere; | 2 4.2.6 General synthetic procedure for compounds 25-29 and 36 General procedure: To a solution of the unsaturated aldehyde 24 (2.4 equiv) and the appropriate diamine in anhydrous dichloromethane (7 mL/mmol of diamine) was added sodium triacetoxyborohydride (3 equiv) portion wise at 0 °C, followed by acetic acid (1.2 equiv). The reaction mixture was stirred at room temperature under an nitrogen atmosphere for 12 h and was then quenched with 20% NaOH solution. The phases were separated and the aqueous layer was extracted three times with 20 mL dichloromethane. The combined organic phases were first washed with brine, then with water and dried over MgSO4. The solvent was removed under reduced pressure to afford the corresponding product, which was used for the next step without further purification. 4.2.6.2 (S)-Benzyl 2,6-bis(2,2-dimethylpent-4-enylamino)-hexanoate (25) Prepared according to the general procedure from 19 (850 mg, 1.83 mmol) and 2,2-dimethyl-4-pentenal 24 (493 mg, 4.39 mmol) yielding 25 (510 mg, 1.19 mmol, 65%) as a pale yellow oil. 1H NMR (CDCl3, 400.1 MHz): δ = 7.30-7.38 (m, 5H), 5.70-5.81 (m, 2H), 5.12-5.16 (m, 2H), 4.95-5.10 (m, 4H), 3.10-3.13 (m, 1H), 2.86-2.90 (m, 2H), 2.38 (d, J = 11.3 Hz, 1H), 2.15 (d, J = 7.8 Hz, 2H), 2.01-2.03 (m, 1H), 1.93-1.96 (m, 2H), 1.76-1.84 (m, 2H), 1.15-1.69 (m, 6H), 1.07 (s, 6H), 0.82 (2* s, total 6H) ppm; 13C NMR (CDCl3, 100.6 MHz): δ = 175.3, 135.8, 134.4, 133.3, 128.5, 128.3, 118.9, 116.8, 66.3, 62.2, 58.1, 57.3, 49.1, 44.3, 43.5, 34.4, 33.5, 32.7, 29.6, 25.2, 25.1, 23.8 ppm; HRMS (ESI): m/z calcd for C27H45N2O2+: 429.3481; found: 429.3454 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With sodium tris(acetoxy)borohydride; acetic acid In dichloromethane at 0 - 20℃; for 12h; Inert atmosphere; | 3 4.2.6 General synthetic procedure for compounds 25-29 and 36 General procedure: To a solution of the unsaturated aldehyde 24 (2.4 equiv) and the appropriate diamine in anhydrous dichloromethane (7 mL/mmol of diamine) was added sodium triacetoxyborohydride (3 equiv) portion wise at 0 °C, followed by acetic acid (1.2 equiv). The reaction mixture was stirred at room temperature under an nitrogen atmosphere for 12 h and was then quenched with 20% NaOH solution. The phases were separated and the aqueous layer was extracted three times with 20 mL dichloromethane. The combined organic phases were first washed with brine, then with water and dried over MgSO4. The solvent was removed under reduced pressure to afford the corresponding product, which was used for the next step without further purification. 4.2.6.3 (S)-Phenethyl 2,6-bis(2,2-dimethylpent-4-enyl-amino)hexanoate (26) Prepared according to the general procedure from 20 (980 mg, 2.05 mmol) and 2,2-dimethyl-4-pentenal 24 (551 mg, 4.92 mmol) yielding 26 (810 mg, 1.83 mmol, 89%) as a pale yellow oil. 1H NMR (CDCl3, 400.1 MHz): δ = 7.28-7.33 (m, 2H), 7.10-7.25 (m, 3H), 5.73-5.88 (m, 2H), 4.97-5.07 (m, 4H), 4.35 (t, J = 7.0 Hz, 2H), 3.03-3.15 (m, 1H), 2.90-2.97 (m, 2H), 2.72 (s, 1H), 2.07-2.36 (m, 5H), 1.95-2.03 (m, 4H), 1.74-1.83 (m, 2H, 3-H), 1.30-1.65 (m, 4H), 0.84 and 0.89 (2* s, total 12H) ppm; 13C NMR (CDCl3, 100.6 MHz): δ = 175.3, 137.1, 134.9, 134.7, 128.3, 127.9, 126.0, 116.5, 116.2, 71.1, 64.2, 50.1, 44.2, 43.8, 42.8, 34.6, 33.8, 33.6, 24.7, 24.6, 23.2 ppm; HRMS (ESI): m/z calcd for C28H47N2O2+: 443.3638; found: 443.3620 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With sodium tris(acetoxy)borohydride; acetic acid In dichloromethane at 0 - 20℃; for 12h; Inert atmosphere; | 4 4.2.6 General synthetic procedure for compounds 25-29 and 36 General procedure: To a solution of the unsaturated aldehyde 24 (2.4 equiv) and the appropriate diamine in anhydrous dichloromethane (7 mL/mmol of diamine) was added sodium triacetoxyborohydride (3 equiv) portion wise at 0 °C, followed by acetic acid (1.2 equiv). The reaction mixture was stirred at room temperature under an nitrogen atmosphere for 12 h and was then quenched with 20% NaOH solution. The phases were separated and the aqueous layer was extracted three times with 20 mL dichloromethane. The combined organic phases were first washed with brine, then with water and dried over MgSO4. The solvent was removed under reduced pressure to afford the corresponding product, which was used for the next step without further purification. 4.2.6.4 (S)-3-Phenylpropyl 2,6-bis(2,2-dimethylpent-4-enyl-amino)hexanoate (27) Prepared according to the general procedure from 21 (1.00 g, 2.03 mmol) and 2,2-dimethyl-4-pentenal 24 (547 mg, 4.87 mmol) yielding 27 (755 mg, 1.65 mmol, 81%) as a yellow-brown oil. 1H NMR (CDCl3, 400.1 MHz): δ = 7.26-7.30 (m, 2H), 7.16-7.21 (m, 3H), 5.73-5.81 (m, 2H), 4.96-5.07 (m, 4H), 4.09-4.15 (m, 2H), 3.08 (dd, J = 7.7 Hz, J = 5.5 Hz, 1H), 2.92-2.96 (m, 2H), 2.66-2.69 (m, 4H), 2.16-2.43 (m, 4H), 1.82-2.09 (m, 8H), 1.32-1.69 (m, 4H), 1.09 (s, 6H), 0.85 (2* s, total 6H) ppm; 13C NMR (CDCl3, 100.6 MHz): δ = 175.4, 140.9, 135.4, 135.2, 128.4, 128.3, 126.0, 117.1, 116.9, 63.9, 62.3, 58.2, 49.1, 44.3, 44.2, 43.3, 34.4, 33.5, 32.8, 32.1, 25.3, 25.2, 23.7, 23.4 ppm; HRMS (ESI): m/z calcd for C29H49N2O2+: 457.3794; found: 457.3758 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With sodium tris(acetoxy)borohydride; acetic acid In dichloromethane at 0 - 20℃; for 12h; Inert atmosphere; | 5 4.2.6 General synthetic procedure for compounds 25-29 and 36 General procedure: To a solution of the unsaturated aldehyde 24 (2.4 equiv) and the appropriate diamine in anhydrous dichloromethane (7 mL/mmol of diamine) was added sodium triacetoxyborohydride (3 equiv) portion wise at 0 °C, followed by acetic acid (1.2 equiv). The reaction mixture was stirred at room temperature under an nitrogen atmosphere for 12 h and was then quenched with 20% NaOH solution. The phases were separated and the aqueous layer was extracted three times with 20 mL dichloromethane. The combined organic phases were first washed with brine, then with water and dried over MgSO4. The solvent was removed under reduced pressure to afford the corresponding product, which was used for the next step without further purification. 4.2.6.5 (S)-Naphthalen-1-yl 2,6-bis((2,2-dimethylpent-4-en-1-yl)amino)hexanoate (28) Prepared according to the general procedure from 22 (765 mg, 1.53 mmol) and 2,2-dimethyl-4-pentenal 24 (412 mg, 3.67 mmol) yielding 28 (638 mg, 1.37 mmol, 90%) as a yellow-orange oil. 1H NMR (CDCl3, 400.1 MHz): δ = 7.85-7.90 (m, 2H), 7.74-7.76 (m, 1H), 7.45-7.54 (m, 3H), 7.25 (d, J = 7.2 Hz, 1H), 5.77-5.91 (m, 2H), 4.99-5.06 (m, 4H), 3.54-3.58 (m, 1H), 2.64-2.69 (m, 3H), 2.32-2.38 (m, 3H), 1.97-2.09 (m, 5H), 1.81-1.89 (m, 1H), 1.56-1.73 (m, 4H), 1.32-1.55 (m, 2H), 0.94 (2* s, total 6H), 0.90 (s, 6H) ppm; 13C NMR (CDCl3, 100.6 MHz): δ = 174.6, 146.6, 135.5, 135.4, 134.7, 128.1, 126.8, 126.4, 126.0, 125.4, 121.1, 118.0, 117.0, 116.8, 62.9, 60.4, 58.5, 50.8, 44.8, 44.5, 34.6, 34.2, 33.7, 29.9, 25.5, 25.4, 25.3, 23.9 ppm; HRMS (ESI): m/z calcd for C30H45N2O2+: 465.3481; found: 465.3484 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With sodium tris(acetoxy)borohydride; acetic acid In dichloromethane at 0 - 20℃; for 12h; Inert atmosphere; | 6 4.2.6 General synthetic procedure for compounds 25-29 and 36 General procedure: To a solution of the unsaturated aldehyde 24 (2.4 equiv) and the appropriate diamine in anhydrous dichloromethane (7 mL/mmol of diamine) was added sodium triacetoxyborohydride (3 equiv) portion wise at 0 °C, followed by acetic acid (1.2 equiv). The reaction mixture was stirred at room temperature under an nitrogen atmosphere for 12 h and was then quenched with 20% NaOH solution. The phases were separated and the aqueous layer was extracted three times with 20 mL dichloromethane. The combined organic phases were first washed with brine, then with water and dried over MgSO4. The solvent was removed under reduced pressure to afford the corresponding product, which was used for the next step without further purification. 4.2.6.6 (S)-4-Methoynaphthalen-1-yl 2,6-bis((2,2-dimethyl-pent-4-en-1-yl)amino)hexanoate (29) Prepared according to the general procedure from 23 (1.00 g, 1.88 mmol) and 2,2-dimethyl-4-pentenal 24 (508 mg, 4.52 mmol) yielding 29 (785 mg, 1.59 mmol, 84%) as a pale brown oil. 1H NMR (CDCl3, 400.1 MHz): δ = 8.24-8.28 (m, 1H), 7.74-7.79 (m, 1H), 7.48-7.55 (m, 2H), 7.11 (d, J = 8.5 Hz, 1H), 6.76 (d, J = 8.3 Hz, 1H), 5.76-5.91 (m, 2H), 4.99-5.07 (m, 4H), 4.00 (s, 3H), 3.51-3.55 (m, 1H), 2.62-2.67 (m, 2H), 2.38 (s, 2H), 2.31-2.35 (m, 1H), 1.93-2.11 (m, 5H), 1.78-1.87 (m, 1H), 1.56-1.74 (m, 5H), 0.90 and 0.93 (2* s, total 12H) ppm; 13C NMR (CDCl3, 100.6 MHz): δ = 174.9, 153.4, 139.9, 135.5, 127.5, 126.9, 126.2, 125.7, 122.5, 120.8, 117.6, 116.9, 116.8, 102.8, 71.7, 62.8, 60.3, 58.5, 55.7, 50.7, 44.8, 44.5, 43.4, 34.6, 34.2, 25.5, 25.4, 25.3, 23.9, 23.8 ppm; HRMS (ESI): m/z calcd for C31H47N2O3+: 495.3587; found: 495.3581 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With sodium tris(acetoxy)borohydride; acetic acid; In dichloromethane; at 0 - 20℃; for 12h;Inert atmosphere; | General procedure: To a solution of the unsaturated aldehyde 24 (2.4 equiv) and the appropriate diamine in anhydrous dichloromethane (7 mL/mmol of diamine) was added sodium triacetoxyborohydride (3 equiv) portion wise at 0 °C, followed by acetic acid (1.2 equiv). The reaction mixture was stirred at room temperature under an nitrogen atmosphere for 12 h and was then quenched with 20percent NaOH solution. The phases were separated and the aqueous layer was extracted three times with 20 mL dichloromethane. The combined organic phases were first washed with brine, then with water and dried over MgSO4. The solvent was removed under reduced pressure to afford the corresponding product, which was used for the next step without further purification. 4.2.6.1 (S)-Methyl 2,6-bis(2,2-dimethylpent-4-enylamino)-hexanoate (36) Prepared according to the general procedure from 2,2-dimethyl-4-pentenal 24 (5.57 g, 49.6 mmol) and l-<strong>[13515-95-2]lysine methyl ester dihydrochloride</strong> 35 (4.82 g, 20.7 mmol) yielding 36 (6.46 g, 18.3 mmol, 89percent) as a pale yellow liquid; (Found: C, 71.16; H, 11.53; N, 7.82. C21H40N2O2 requires C, 71.54; H, 11.44; N, 7.95percent); 1H NMR (CDCl3, 400.1 MHz): delta = 5.73-5.87 (m, 2H), 4.97-5.06 (m, 4H), 3.69 (s, 3H), 3.12 (t, J = 6.8 Hz, 1H), 2.52 (t, J = 6.8 Hz, 2H), 2.34 (d, J = 11.3 Hz, 1H), 2.32 (s, 2H), 2.07 (d, J = 11.5 Hz, 1H), 1.95-2.02 (m, 4H), 1.29-1.65 (m, 6H), 0.84 and 0.88 (2* s, total 12H) ppm; 13C NMR (CDCl3, 100.6 MHz): delta = 176.2, 135.3, 116.6, 116.5, 62.3, 60.2, 58.0, 51.3, 50.5, 44.5, 44.1, 34.2, 34.0, 33.3, 29.6, 25.3, 25.1, 25.0, 23.6 ppm. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With sodium tris(acetoxy)borohydride; acetic acid In dichloromethane at 0 - 20℃; for 12h; Inert atmosphere; | (S)-(Anthraquinon-2-yl)methyl 2,6-bis(2,2-dimethylpent-4-enyl-amino)-hexanoate (7) To a solution of the unsaturated aldehyde 6 (92 mg, 0.82 mmol, 2 equiv.) and TFA salt 5 (243 mg, 0.41 mmol) in anhydrous dichloromethane (20 mL) was added sodium triacetoxyborohydride (260 mg, 1.23 mmol, 3 equiv.) portion wise at 0 °C, followed by acetic acid (47 μL, 0.82 mmol, 2 equiv.). The reaction mixture was stirred at room temperature under an nitrogen atmosphere for 12 h and was then quenched with 20% NaOH solution. The phases were separated and the aqueous layer was extracted three times with 20 mL dichloromethane. The combined organic phases were first washed with brine, then with water and dried over MgSO4. The solvent was removed under reduced pressure to afford the diamine 7 (219 mg, 0.39 mmol, 96%), which was used for the next step without further purification. 1H NMR (CDCl3, 400.1 MHz): δ = 8.29-8.33 (m, 3H), 8.27-8.29 (m, 1H), 7.78-7.83 (m, 2H), 7.75-7.77 (m, 1H), 5.72-5.83 (m, 2H), 5.26-5.34 (m, 2H), 4.98-5.00 (m, 2H), 4.95-4.97 (m, 2H), 3.22-3.26 (m, 1H), 2.52-2.56 (m, 2H) 2.41 (d, J = 11.5 Hz, 1H), 2.31 (s, 1H), 2.14 (d, J = 11.5 Hz, 1H), 1.96-1.99 (m, 4H), 1.34-1.72 (several overlapping signals, 9H), 0.85 and 0.84 (2 × s, total 12 H) ppm; 13C NMR (CDCl3, 100.6 MHz): δ = 182.8, 182.7, 175.6, 142.7, 135.5 (2 × C), 134.3, 134.2, 133.7, 133.4, 133.1, 133.0, 132.8, 127.7, 127.3, 126.2, 116.8, 116.7, 71.7, 65.1, 62.5, 58.3, 50.6, 44.7, 44.4, 43.4, 34.5, 34.2, 33.9, 25.6, 25.5, 25.3, 25.2, 23.8, 23.7 ppm; HRMS (ESI): m/z calcd for C35H47N2O4+: 559.3530; found: 559.3531 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | With titanium(IV) tetraethanolate In dichloromethane at 20℃; for 18h; | Preparation of intermediate F1 Preparation of intermediate F1 To a mixture of 2,2-dimethyl-4-pentanal (3.68 g, 32.8 mmol) and 2-methyl-2- propanesulfinamide (4.77 g, 39.4 mmol) in anhydrous CH2CI2 (225 mL) was added drop-wise titanium(IV) ethoxide (9.8 mL, 39.4 mmol) at rt. The resulting mixture was stirred at rt for 18 h. Water was added portion-wise until all precipitation of T1O2 and the mixture was filtered over celite. The filtrate was decanted and the organic layer was washed with water (once). The organic layer was dried over MgS04, filtered and the solvent was removed in vacuo. The crude was purified by preparative silica LC (mobile phase gradient: heptane/EtOAc: 95/5 to 70/30) to give 4.89 g of F1 as a colorless oil (69%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With (bis(diisopropylphenyl-imidazol-2-ylidene)phenyl)CoN<SUB>2</SUB> In benzene at 20℃; for 4.5h; chemoselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With (bis(diisopropylphenyl-imidazol-2-ylidene)phenyl)CoN<SUB>2</SUB> In benzene at 20℃; for 7h; chemoselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | With 1,4-diaza-bicyclo[2.2.2]octane In neat (no solvent) at 80℃; for 12h; | 4.2. General Procedure B for Passerini-Smiles Reaction with 2-Fluoro-4-nitrophenol Derivatives General procedure: To 1.0 equiv. of phenol were added successively 1.0 equiv. of DABCO, 2.0 equiv. of aldehyde, and 1.0 equiv. of isocyanide. The resulting mixture was stirred neat at 80 °C for 12 h. The crude product was dissolved in dichloromethane. The organic layer was washed with 1 M NaOH, water, dried over MgSO4 and then concentrated. The crude product was purified by flash chromatography on silica gel. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
20 g | With magnesium In tetrahydrofuran; toluene at 20℃; Inert atmosphere; | Example 6a: (1S*,2S*)-2,6,6-trimethylcyclohex-3-en-1-yl (E)-but-2-enoate and comparitive example 6b (1S*,2R*)-2,6,6-trimethylcyclohex-3-en-1-yl (E)-but-2-enoate a) A few m of a souDon of (E)-1-chorobut-2-ene (25.6 g, 282 mmoD n THF (200 mD were added to rnagnesum turnings (8.58 g, 353 rnrnofl ri THF (100 mfl under argon atmosphere. After the reaction had started, the rest of the chorobutene soufion was added dropwse. The mixture was aflowed to coo’ to room temperature and a souton of 2,2-dmethypent-4-ena (40.0 g, 66% souton n touene, 235 mmo) n THF (50 mD was added sowy. The mixture was coo’ed to 0°C and quenched with aq. NH4C (200 mD, The organic ayer was separated and the aqueous ayer was extracted wfth ethy acetate (3 x 200 mL). The combined organic ayers were washed wfth brine, dried (MgSO4) and concentrated n vacuo. The residue was dstWed bub-to-bub (014 mbar, 140 °C) to yed 20Og of 3,5,5-trmethyocta-1 ,7-den-4-o as a cooress oH. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With oxygen at 110℃; Schlenk technique; Green chemistry; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With oxygen at 110℃; for 48h; Schlenk technique; Green chemistry; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | With oxygen at 110℃; for 48h; Schlenk technique; Green chemistry; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
52% | Stage #1: nitromethane; 2,2-dimethyl-4-pentenal With triethylamine at 20 - 25℃; Inert atmosphere; Schlenk technique; Stage #2: With trifluoroacetic anhydride In dichloromethane at -78℃; for 0.0833333h; Inert atmosphere; Schlenk technique; Stage #3: With N-ethyl-N,N-diisopropylamine In dichloromethane at -78 - 25℃; Inert atmosphere; Schlenk technique; | 4.3.11 (E)-1-nitro-2,2-dimethyl-hexa-1,5-diene (17) A solution of 2,2-dimethylpent-4-enal (2.00mL, 14.7mmol), triethylamine (1.03mmol, 0.35 equiv.) and nitromethane (4.00mL, 74.1mmol, 5.0 equiv.) was stirred overnight under N2 at rt. The nitromethane and trimethylamine were removed in vacuo; purification by silica plug gave nitroalcohol which was used directly in the next step. To a solution of the purified nitroalcohol (14.7mmol) in dry DCM (45mL) under N2 at-78°C was added TFAA (17.6mmol, 1.2 equiv.) dropwise and the reaction stirred for 5min before the dropwise addition of DIPEA (36.8mmol, 2.50 equiv.). The reaction was stirred at - 78°C until complete reaction (tlc) before warming to rt. The reaction was quenched with 2M HCl (50mL) extracted with CH2Cl2 (50mL x 3), washed with sat. NaCl solution (50mL), dried (MgSO4) filtered and conc in vacuo. Purification by flash column chromatography (2% EtOAc/Hexanes) afforded 17 as a colourless oil (1.19g, 7.67mmol, 52%); IR νmax (thin film) 2966 (C-H) 1642 (C=C) 1524 (N-O, asymm) 1348 (N-O, symm) cm-1; 1H NMR (CDCl3, 500MHz) δ 1.13 (6H, s, C(CH3)2) 2.18 (2H, apt dt, J=7.4, 1.0, CCH2) 5.07 (1H, dm, J=17.0, CH2CHCH2-trans) 5.12 (1H, dm, J=10.2, CH2CHCH2-cis) 5.70 (1H, ddt, J=17.0, 10.3, 7.4, CH2CH) 6.88 (1H, d, J=13.6, CHCHNO2) 7.25 (1H, d, J=13.7, CHCHNO2); 13C NMR (CDCl3, 125MHz) δ 26.1 (2C, CH3) 35.9 (q, C(CH3)2) 46.3 (C(CH3)2CH2) 119.0 (CCH2CHCH2) 133.1 (CHCH2) 138.0 (CHNO2) 150.9 (CHCHNO2); m/z (ESI+) 194.1 (6%, M+K+) 178.1 (72%, M+Na+) 156.1 (100%, M+H+); HRMS C8H14NO2 calcd. 156.1024 found 156.1030. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With [PAIM][NTf2]; 3-butyl-1-methyl-1H-imidazol-3-ium hexafluorophosphate at 20℃; for 1.5h; Inert atmosphere; | General procedure for the epoxidation reaction: General procedure: An oven-dried 25mL reaction tube equipped with magnetic stir bar was charged with IL solvent [BMIM][BF4] or [BMIM][PF6] (5-6 mL) and the carbonyl compound (1 mmol) under nitrogen. After stirring for 10-15 minutes at r.t., trimethylsulfonium iodide (1.1 mmol) and Basic-IL [PAIM][NTf2] (20 mol%) were added and the reaction mass was stirred for the specified time (see Table 2). The progress of the reaction was monitored by TLC and by GC-MS. Upon completion, the reaction mixture was extracted with Et2O (310mL) and the combined organic phase was dried over anhydrous sodium sulfate. The solvent was removed under vacuum and the crude products were purified by flash column chromatography with hexane-ethyl acetate mixture (80:20) to afford pure compounds. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | at 20℃; for 14h; Inert atmosphere; | 2,2-Dimethyl-4-pentenal-N,N-dimethylhydrazone (4b’) A 20 mL round-bottomed flask equipped with a magnetic stirring bar and an N2 inlet was charged with 2,2-dimethyl-4-pentenal7 (2.6 g, 23 mmol) and N,N-dimethylhydrazine (2.2 mL, 28 mmol). The reactant mixture was stirred at room temperature for 12 h. The resulting water layer was removed and KOH pellets (2.0 g) were added to the reaction mixture. The solution was stirred for an additional 2 h then filtered through a pad of Celite. Excess N,N-dimethylhydrazine was removed in vacuo and the concentrate was purified by short path distillation from CaH2 to provide 3.00 g (85%) of the title compound as a clear liquid. 1H NMR (500 MHz, CDCl3): δ 6.56 (s, 1H), 5.81 (ddt, J = 7.3, 10.7, 14.5 Hz, 1H), 5.08-4.97 (m, 2H), 2.71 (s, 6H), 2.16 (dt, J = 1.2, 7.3 Hz, 2H), 1.06 (s, 6H). 13C NMR (500 MHz, CDCl3): δ 146.0, 135.3, 116.9, 46.0, 43.4, 37.1, 25.9. |
85% | at 20℃; for 12h; Inert atmosphere; | 2,2-Dimethyl-4-pentenal-N,N-dimethylhydrazone (4b’) A 20 mL round-bottomed flask equipped with a magnetic stirring bar and an N2 inlet was charged with 2,2-dimethyl-4-pentenal7 (2.6 g, 23 mmol) and N,N-dimethylhydrazine (2.2 mL, 28 mmol). The reactant mixture was stirred at room temperature for 12 h. The resulting water layer was removed and KOH pellets (2.0 g) were added to the reaction mixture. The solution was stirred for an additional 2 h then filtered through a pad of Celite. Excess N,N-dimethylhydrazine was removed in vacuo and the concentrate was purified by short path distillation from CaH2 to provide 3.00 g (85%) of the title compound as a clear liquid. 1H NMR (500 MHz, CDCl3): δ 6.56 (s, 1H), 5.81 (ddt, J = 7.3, 10.7, 14.5 Hz, 1H), 5.08-4.97 (m, 2H), 2.71 (s, 6H), 2.16 (dt, J = 1.2, 7.3 Hz, 2H), 1.06 (s, 6H). 13C NMR (500 MHz, CDCl3): δ 146.0, 135.3, 116.9, 46.0, 43.4, 37.1, 25.9. |
Tags: 5497-67-6 synthesis path| 5497-67-6 SDS| 5497-67-6 COA| 5497-67-6 purity| 5497-67-6 application| 5497-67-6 NMR| 5497-67-6 COA| 5497-67-6 structure
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P403 + P235 | Store in a well-ventilated place. Keep cool. |
P410 + P403 | Protect from sunlight. Store in a well-ventilated place. |
P410 + P412 | Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF. |
P411 + P235 | Keep cool. |
Disposal | |
Code | Phrase |
P501 | Dispose of contents/container to ... |
P502 | Refer to manufacturer/supplier for information on recovery/recycling |
Physical hazards | |
Code | Phrase |
H200 | Unstable explosive |
H201 | Explosive; mass explosion hazard |
H202 | Explosive; severe projection hazard |
H203 | Explosive; fire, blast or projection hazard |
H204 | Fire or projection hazard |
H205 | May mass explode in fire |
H220 | Extremely flammable gas |
H221 | Flammable gas |
H222 | Extremely flammable aerosol |
H223 | Flammable aerosol |
H224 | Extremely flammable liquid and vapour |
H225 | Highly flammable liquid and vapour |
H226 | Flammable liquid and vapour |
H227 | Combustible liquid |
H228 | Flammable solid |
H229 | Pressurized container: may burst if heated |
H230 | May react explosively even in the absence of air |
H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
H240 | Heating may cause an explosion |
H241 | Heating may cause a fire or explosion |
H242 | Heating may cause a fire |
H250 | Catches fire spontaneously if exposed to air |
H251 | Self-heating; may catch fire |
H252 | Self-heating in large quantities; may catch fire |
H260 | In contact with water releases flammable gases which may ignite spontaneously |
H261 | In contact with water releases flammable gas |
H270 | May cause or intensify fire; oxidizer |
H271 | May cause fire or explosion; strong oxidizer |
H272 | May intensify fire; oxidizer |
H280 | Contains gas under pressure; may explode if heated |
H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
H290 | May be corrosive to metals |
Health hazards | |
Code | Phrase |
H300 | Fatal if swallowed |
H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
H304 | May be fatal if swallowed and enters airways |
H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
H313 | May be harmful in contact with skin |
H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
Sorry,this product has been discontinued.
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