Acylammonium Salts as Dienophiles in Diels−Alder/Lactonization

ABSTRACT: α,β-Unsaturated acylammonium salts, gen-erated in situ from commodity acid chlorides and a chiral isothiourea organocatalyst, comprise a new and versatile family of chiral dienophiles for the venerable Diels−Alder (DA) cycloaddition. Their reactivity is unveiled through a highly diastereo- and enantioselective Diels−Alder/lacto-nization organocascade that generates cis- and trans-fused bicyclic γ- and δ-lactones bearing up to four contiguous stereocenters. Moreover, the first examples of DA-initiated, stereodivergent organocascades are described delivering complex scaffolds found in bioactive compounds. The origins of stereoselectivity are rationalized through computational studies. In addition, the utility of this methodology is demonstrated through a concise approach to the core structure of glaciolide and formal syntheses o