Selective access to both diastereoisomers in an enantioselective intramolecular Michael reaction by using a single chiral organocatalyst and application in the formal total synthesis of (-)-epibatidine.

Two in one: Both diastereoisomers of 4-nitro-3-substituted cyclohexanones are accessed selectively by an intramolecular Michael reaction using a single chiral aminocatalyst (see scheme). Mechanistic studies show that the reaction is selective for the cis-diastereoisomer and that the trans-diastereoisomer arises over time. DFT calculations suggest that the cis-selectivity is due to a favorable electrostatic interaction between the iminium ion and the nucleophile.