Enantioselective Organocatalytic Conjugate Addition in a Tandem Synthesis of δ-Substituted Cyclohexenones and Four-Step Total Synthesis of Penienone

A bisperfluorotoluyl-BINOL catalyzed conjugate addition of trifluoroborate salts to doubly vinylogous esters and aldol condensation synthesized chiral 6-substituted cyclohexenones with high yields and enantioselectivities (10 examples, up to 89% yield, 89-98% ee). Stepwise and single-pot sequences were developed, with the former also providing beta-substituted masked ketoaldehydes containing a vinyl ether. The transformation was used in a four-step total synthesis of penienone (24% overall yield), <= half the steps as in previous syntheses.

Automated summary

A chiral 6-substituted cyclohexenone was synthesized with high yields and enantioselectivities through a bisperfluorotoluyl-BINOL catalyzed conjugate addition of trifluoroborate salts to doubly vinylogous esters and aldol condensation. Stepwise and single-pot sequences were developed, with the former also providing beta-substituted masked ketoaldehydes containing a vinyl ether. This transformation was used in a four-step total synthesis of penienone with a significantly reduced number of steps compared to previous syntheses.