Stereoselective palladium-catalyzed functionalization of homoallylic alcohols: a convenient synthesis of di- and trisubstituted isoxazolidines and β-amino-δ-hydroxy esters.

Abstract

Enantiopure, Boc-protected alkoxyamines 12 and 13, derived from the readily available homoallylic alcohols 4 via a reaction that involves either inversion or retention of configuration, undergo a diastereoselective Pd-catalyzed ring-closing carbonylative amidation to produce isoxazolidines 16/17 (≤50:1 diastereoisomer ratio (d.r.)) that can be readily converted into the N-Boc-protected esters of β-amino-δ-hydroxy acids and their γ-substituted homologues 37. The key carbonylative cyclization proceeds through an unusual syn addition of the palladium and the nitrogen nucleophile across the C=C bond (19→21), as revealed by the reaction of 15, which afforded isoxazolidine 18 with high diastereoselectivity.