Efficient Access to All-Carbon Quaternary and Tertiary alpha-Functionalized Homoallyl-type Aldehydes from Ketones

Widely substituted all-carbon quaternary and tertiary α-homoallyl aldehydes are rapidly assembled through a unique synthetic operation from ketones consisting in: 1) C1-homologation; 2) epoxide-aldehyde Lewis acid mediated isomerization and, 3) electrophilic trapping. The synthetic equivalence between a vinyl oxirane and a β,γ-unsaturated aldehyde is the key concept for introducing such a previously undisclosed tactic. Mechanistic studies and labeled experiments suggest the intervention of an aldehyde enolate as the crucial intermediate. Significantly, the homologating carbenoid formation event (carbenoid precursor and organolithium) plays a critical role in determining the chemoselectivity.