Trans-2-Phenylcyclohexanol

The other enantiomer, (+)-(1S,2fl)-trans-2-phenylcyclohexanol, was also prepared by this procedure. The crude mass of the alcohol was 39.15 g (95.8% ee), while after recrystalli/ration, the yield was 29.80 g (69%) of materieil with the following properties mp 64-66°G, >99.5% ee (see Note 7 for data). The reaction appears to be scaleable... 

In scaling up this procedure, the biggest improvement in the overall yield was achieved by omitting the crystallization of the intermediate diol. The trans-2-phenylcyclohexanol, which forms relatively large crystals, is easier to handle lhan the diol, which is a very fluffy powder. Analysis of the final product was carried out by both CSP-HPLC and CSP-SFC methods. 

SYNTHESIS OF (+)-(1S,2fl)- AND -H1B,2S)-trans-2-PHENYLCYCLOHEXANOL VIA SHARPLESS ASYMMETRIC DIHYOROXYLATION (AD)... 

Enantiomerically pure trans-2-phenylcyclohexanol, first used by Whitesell as a chiral auxiliary has become a popular reagent in a number of asymmetric transformations. Some recent applications include asymmetric azo-ene reactions, [4 + 2]-cycloaddition reactions, ketene-olefin [2 + 2]-reactions, enolate-imine cyclocondensations, Pauson-Khand reactions," palladium annulations and Reformatsky reactions. Despite its potential, use of this chiral auxiliary on a preparative scale is currently limited by its prohibitive cost. 

The Birch reduction of dibenzofuran is reported to give 1,4-dihydro-dibenzofuran. The electrochemical reduction of dibenzofuran by solvated electrons is reported to produce a dihydrodibenzofuran and a tetrahydro-dibenzofuran, both of unspecified structure. Treatment of dibenzofuran with W-7 Raney nickel in boiling methanol gave a moderate yield of trans-2-phenylcyclohexanol, whereas treatment of dibenzofuran with Raney nickel alloy and aqueous sodium hydroxide gave a low yield of 2-biphenylol. ... 

The technique of chiral auxiliaries was exploited in a synthesis of cholesterol absorption inhibitors, based on an imino-Reformatsky reaction between bromoacetates of chiral alcohols (e.g. 69a and 69b) and imine 70. Virtual complete asymmetric induction was found with (-)-trans-2-phenylcyclohexanol and (—)-phenyl substituted menthol derived chiral auxiliaries (equation 43)126. 

Because of the lack of ready access to 2, Whitesell et al.2 recommend trans-2-phenylcyclohexanol (3) as an auxiliary. Hydrolysis of the acetate of ( + )-3 with hog liver esterase provides optically pure (- )-3,aD - 56° and (+ )-3,aD + 54°. The glyoxylate ester of 3 undergoes ene reactions with high diastereoselectivity. 

LIPASE-CATALYZED KINETIC RESOLUTION OF ALCOHOLS VIA CHLOROACETATE ESTERS (-)-(1R,2S)-trans-2-PHENYLCYCLOHEXANOL AND (+)-(1S,2R)-trans-2-PHENYLCYCLOHEXANOL... 

B. Racemic trans-2-phenylcyclohexyl chloroacetate. A 1-L, round-bottomed flask equipped with a magnetic stirrer and a condenser is charged with 100 g (0.567 mol) of racemic trans-2-phenylcyclohexanol, 50 mL (0.625 mol) of chloroacetyl chloride (Note 9), 300 mg (0.0025 mol) of 4-dimethylaminopyridine (DMAP) (Note 10) and 250 mL of dichloromethane. This mixture is rapidly stirred and heated at reflux for 6 hr. The mixture Is cooled and a solution of 350 mL of saturated sodium bicarbonate is carefully added to the rapidly stirring mixture (Note 11). Stirring is maintained for 3... 

D. (+)-(1S,2R)-trans-2-Phenylcyclohexanol. A 500-mL, round-bottomed flask is charged with a mixture of 52.0 g (0.206 mol) of (+)-(1S,2R)-trans-2-phenylcyclohexyl chloroacetate, 250 mL of 2 N sodium hydroxide, and 100 mL of methanol and then stirred at reflux for 3 hr. TLC analysis (Note 24) indicates complete reaction. The mixture is cooled to room temperature, adjusted to pH 7 with -35 mL of 3 N sulfuric acid and poured into 500 mL of water. The mixture is extracted with two 150-mL portions of dichloromethane and the organic layer is dried over anhydrous sodium sulfate and concentrated on a rotary evaporator (35°C) to afford 37.0 g of a colorless solid. Recrystallization from 100 mL of petroleum elher (30-60°C) at -20°C gives in... 

The procedure described here provides ready access to both the (+)- and (-) antipodes of trans-2-phenylcyclohexanol, a useful chiral auxiliary in ene reactions of its glyoxylate ester4 and its N-sulfinylcarbamate,5 as well as in cycloaddition reactions... 

Optically pure trans-2-phenylcyclohexanol can also be prepared by resolution of the phthalate esters using brucine to obtain the (-t-)-alcohol and strychnine to obtain the (-)-alcohol (after basic hydrolysis of their respective salts).11 Enzyme-catalyzed kinetic resolution of the acetate esters using pig liver esterase4 and pig liver acetone powder12 has been used to prepare both enantiomers of this chiral auxiliary. The hydroboration of 1-phenylcyclohexene with isopinocampheylborane has been reported to give the chiral auxiliary in 97% enantiomeric excess.13... 

Racemic trans-2-phenylcyclohexanol has previously been prepared in a yield comparable to that realized in this procedure via copper-catalyzed phenyl Grignard addition to cyclohexene oxide using the more expensive copper(l) oxide.14... 

Racemic trans-2-Phenylcyclohexanol Cyclohexanol, 2-phenyl-, trans-( )- (9) (40960-69-8)... 

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