Asymmetric Hydrative Aldol Reaction (HAR) via Vinyl-Gold Promoted Intermolecular Ynamide Addition to Aldehydes

Angew Chem Int Ed Engl. 2023 Aug 1;62(31):e202305810. doi: 10.1002/anie.202305810. Epub 2023 Jun 23.

Abstract

Herein, we reported an intermolecular asymmetric hydrative aldol reaction through vinyl-gold intermediate under ambient conditions. This tandem alkyne hydration and sequential nucleophilic addition afforded a "base-free" approach to β-hydroxy amides with high efficiency (up to 95 % yields, >50 examples). Vinyl gold intermediate was applied as reactive nucleophile and Fe(acac)3 was used as the critical co-catalyst to prevent undesired protodeauration, allowing this transformation to proceed under mild conditions with good functional group tolerance and excellent stereoselectivity (>20 : 1 d.r. and up to 99 % ee).

Keywords: Asymmetric Catalysis; Gold Catalysis; Stereoselective Hydrative Aldol Reaction; Vinyl Gold; Ynamide.