Highly Diastereodivergent Synthesis of Tetrasubstituted Cyclohexanes Catalyzed by Modularly Designed Organocatalysts

A highly diastereodivergent synthesis of tetrasubstituted cyclohexanes has been achieved using modularly designed organocatalysts (MDOs) which are self-assembled in situ from amino acids and cinchona alkaloid derivatives. Diastereodivergence is realized through controlling the stereoselectivity of the individual steps of a tandem Michael/Michael reaction. Up to 8 of the 16 possible stereoisomers have been successfully obtained in high stereoselectivities using MDOs for the tandem reaction and an ensuing epimerization. The method was used in the enantioselective synthesis of the natural products (-)-alpha- and beta-lycoranes.