The Stereoselectivity of the α‐Alkylation of (+)‐(1__R__, 2__S__)‐cis‐Ethyl‐2‐hydroxy‐cyclohexanecarboxylate
In continuation of our work on the stereoselectivity of the α‐alkylation of β‐hydroxyesters [1] [2], we studied this reaction with the title compound (+)‐2. The latter was prepared through reduction of 1 with baker's yeast. Alkylation of the dianion of (+)‐2 furnished (−)‐4 in 72% chemical yield (Scheme 1) and with a stereoselectivity of 95%. Analogously, (−)‐7 was prepared with similar yields. Oxidation of (−)‐4 and (−)‐7 respectively furnished the ketones (−)‐6 (Scheme 3) and (−)‐8 (Scheme 4) respectively, each with about 76% enantiomeric excess (NMR.). It is noteworthy that yeast reduction of rac‐6 (Scheme 3) is completely enantioselective with respect to substrate and product and gives optically pure (−)‐4 in 10% yield, which was converted into optically pure (−)‐6 (Scheme 3).
The alkylation of the dianionic intermediate shows a higher stereoselectivity (95%) from the pseudoequatorial side than that of 1‐acetyl‐ or 1‐cyano‐4‐t‐butyl‐cyclohexane (71% and 85%) [9] or that of ethyl 2‐methyl‐cyclohexanecarboxylate (82%). The stereochemical outcome of the above alkylation is comparable with that found in open chain examples [1] [2].
Finally (+)‐(1__R__, 2__S__)‐2 was also alkylated with Wichterle's reagent to give (−)‐(1__S__, 2__S__)‐9 in 64% yield. The latter was transformed into (−)‐(S)‐10 and further into (−)‐(S)‐11 (Scheme 5). (−)‐(S)‐10 and (−)‐(S)‐11 showed an e.e. of 76–78% (see also [11]). Comparison of these results with those in [11] confirmed our former stereochemical assignment concerning the alkylation step.