Synthesis of Vicinal Aminoalcohols by Stereoselective Aza-Wacker Cyclizations: Access to (—)-Acosamine by Redox Relay

摘要

The stereoselective synthesis of vicinal aminoalcohols from simple starting materials is a prominent challenge in organic chemistry. The prevalence of the vicinal aminoalcohol moiety in biologically active molecules, as well as the challenge in accessing the 1,2-oxidation pattern, has justified the development of a diverse array of synthetic approaches to this functionality. Intermolecular oxidative difunctionalization of alkenes is an appealing strategy for the generation of the 1,2-aminooxygenation pattern, but methods with a combination of high stereo- and regioselectivity,and diverse scope remain elusive. Examples include Sharpless asymmetric aminohydroxylation, metal-catalyze'd activation of oxazir-idines,and palladium-catalyzed aminoacetoxylation reactions which employ hypervalent iodine oxidants. Our interest in palladium-catalyzed aerobic oxidation of alkenes (Wacker-type reactions) prompted us to investigate new methods for the synthesis of vicinal aminoalcohols from readily available, stereochemically defined starting materials. Herein, we employ a detachable, tethered nitrogen nucleo-phile to generate the 1,2-aminooxygenation pattern from allylic alcohols by an aza-Wacker cyclization (Scheme 1 a). The cyclization step forms five-membered oxazolidine products and exhibits high levels of diastereoselectivity. This strategy is amenable to the de novo synthesis of aminosugars, which are key substructures of several antibiotic and anticancer natural products (Scheme 1b). Implementation of a redox-relay approach enables rapid synthesis of (—)-acosamine and highlights the utility of this method.