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

Abstract

A bisperfluorotoluyl–BINOL catalyzed conjugate addition of trifluoroborate salts to doubly vinylogous esters and aldol condensation synthesized chiral δ-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 β-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.

Enantioselective Total Synthesis of Cannabinoids via a Tandem Conjugate Addition/Enolate Alkylation Annulation with Ambiphilic Organoboronates

“…We were then eager to combine the conjugate addition and alkylation into a single reaction. 26 An ideal solvent would replicate the polar aprotic properties of THF for the enolate alkylation annulation while having the noncoordinating nature and increased boiling point of 1,2-dichloroethane or toluene to ensure a good performance in the conjugate addition. 27 2-MeTHF, an ecologically friendly solvent, 28,29 was found to be the perfect bridge between these two solvent characteristics.…”

“…Potassium tert -butoxide was the most effective of those considered, as it gave both a high yield and excellent diastereoselectivity (entry 4). We were then eager to combine the conjugate addition and alkylation into a single reaction . An ideal solvent would replicate the polar aprotic properties of THF for the enolate alkylation annulation while having the noncoordinating nature and increased boiling point of 1,2-dichloroethane or toluene to ensure a good performance in the conjugate addition .…”