Chiral auxiliary cyclohexanol derivative

A further attempt has been made to develop a predictive model for chirality transfer achieved through alkylation reactions of ester enolates which feature chiral auxiliaries. " Hippurate esters (30) derived from (lI , 25 )-trani-2-(p-substituted phenyl)cyclohexanols were found, on reaction with benzyl bromide, to give (31) with predominantly the S configuration at the alkylation centre but with no correlation between the degree of stereoselectivity (20-98%) and the electron density on the aromatic ring. 

The Birch reduction has been applied to electron-deficient pyrroles substituted with a chiral auxiliary at the C(2)-position <1999TL435>. Using either (—)-8-phenylmenthol or (- -)-/ra /-2-(ot-cumyl)cyclohexanol as auxiliaries, high levels of stereoselectivity were obtained. Pyrrole 911, prepared from the l/7-pyrrole-2-carboxylic acid 910 in 90% yield, was reduced under modified Birch conditions (Scheme 176). The best conditions involved lithium metal (3 equiv), liquid ammonia and THE at —78°C. The addition of A, A -bis(2-methoxyethyl)amine (10 equiv) helped to reduce side reactions caused by the lithium amide formed in the reaction <1998TL3075>. After 15 min, the Birch reductions were quenched with a range of electrophiles and in each case 3,4-dehydroproline derivatives 912 were formed in excellent yields and with good diastereoselectivities. 

K. Laumen, D. Breitgoff, R. Seemayer, M.P. Schneider, Enantiomerically pure cyclohexanols and cyclohexane-1,2-diol derivatives chiral auxiliaries and substitutes for (-)-8-phenylmenthol. A facile enzymatic route, 1. Chem. Soc. Chem. Commun. (1989) 148-150. 

An important advantage of enol ether dienophiles is their use in asymmetric synthesis through attachment to a chiral auxiliary. Vinyl ethers derived from (+)-camphor, (l/ ,25)-2-phenylcyclohexanol, (7 )-2,2-diphenylcyclopenta-nol, and (l/ ,25)-2-(l-methyl-l-phenylethyl)cyclohexanol... 

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