Diastereoselective synthesis of γ,γ-disubstituted β-hydroxy α,α-difluoro-γ-butyrolactones

Abstract

The L-proline catalyzed synthesis of α,α-difluoro homoallylic aldehydes was modified, and these aldehydes bearing either aromatic or aliphatic groups the γ-position were obtained with excellent E/Z selectivity (E/Z ≥ 20/1) in a practical manner. Thereafter, the obtained aldehydes were readily transformed into α,α-difluoro homoallylic esters in moderate yields (53–74%) over three steps, maintaining excellent E/Z selectivity (E/Z ≥ 20/1). These esters can be subjected to epoxidation with m-chloroperoxybenzoic acid to generate 3,4-epoxyesters in-situ, which can be treated with an aqueous NaOH to obtain γ,γ-disubstituted β-hydroxy α,α-difluoro-γ-butyrolactones in low to moderate isolated yields (20–72%) with excellent diastereoselectivity (d.r. ≥ 20/1).