Intramolecular Diels–Alder (IMDA) Studies toward the Synthesis of Australifungin. Stereocontrol in the Acetate Aldol Reaction of β,β′-Branched Aldehydes

• DOI: 10.1021/acs.orglett.5b03463
• Publication Date: 2016-01-19T12:34:43Z
• Authors: David R. Williams; J. Cullen Klein
• Keywords: Aldol reaction; Nitroalkene; Diels–Alder reaction; Aldol condensation; Decalin

Studies of australifungin illustrate an enantiocontrolled synthesis the trans-decalin core 28 via intramolecular [4π + 2π] cycloaddition. This strategy utilizes nitroalkene dienophile 27 as a surrogate ketene equivalent. Stereocontrol at C-2 is critically important for effective Diels–Alder (IMDA) process. Our studies report high asymmetric induction using nonracemic Duthaler titanium enolate in acetate aldol reaction with β,β′-branched aldehyde 13 to introduce required chirality.