Enantioselective Total Synthesis of (−)-Hunterine A Enabled by a Desymmetrization/Rearrangement Strategy

Abstract

The first enantioselective total synthesis of (−)-hunterine A is disclosed. Our strategy employs a catalytic asymmetric desymmetrization of a symmetrical diketone and subsequent Beckmann rearrangement to construct a 5,6-α-aminoketone. A convergent 1,2-addition joins a vinyl dianion nucleophile and the enantioenriched ketone. The endgame of the synthesis features an aza-Cope/Mannich reaction and azide-olefin dipolar cycloaddition to complete the pentacyclic ring system. The synthesis is completed through a regioselective aziridine ring opening.This article is licensed under CC-BY-NC-ND 4.0 * sı Supporting InformationThe Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/jacs.3c13590.Experimental procedures, spectroscopic data ( 1 H NMR, 13 C NMR, IR, and HRMS), and crystallographic data (PDF)