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

Abstract

β,γ-Unsaturated aldehydes with all-carbon quaternary or tertiary α-centers were rapidly assembled from ketones through a unique synthetic operation consisting of 1) C₁ homologation, 2) Lewis acid mediated epoxide-aldehyde isomerization, and 3) electrophilic trapping. The synthetic equivalence of a vinyl oxirane and a β,γ-unsaturated aldehyde is the key concept of this previously undisclosed tactic. Mechanistic studies and labeling experiments suggest that an aldehyde enolate is a crucial intermediate. The homologating carbenoid formation plays a critical role in determining the chemoselectivity.

Keywords: aldehydes; carbenoids; enolates; homologation; isomerization.