Synthesis of an enantiopure 2-arylcyclohexanols from prochiral enol acetates by an enantioselective protonation/diastereoselective reduction sequence

The enantioselective protonation with 2-sulfinyl alcohols of lithium enolates of 2-arylcyclohexanones with different substituents on the phenyl group takes place with excellent enantioselectivities (89-99%). Chiral 2-phenylcyclohexanone and 2-arylcyclohexanones carrying electron donor substituents on the aromatic ring are converted into the corresponding trans-2-arylcyclohexanols by diastereoselective reduction with sodium naphthalenide in the presence of acetamide. The stereochemical integrity of the tertiary stereocenter is fully preserved using this reduction procedure. Interestingly, the chiral proton source is not consumed in the synthesis.