Catalytic Asymmetric Cycloaddition of Olefins with In Situ Generated -Boc-Formaldimine.

Chiral 1,3-amino alcohols are ubiquitous structural motifs in natural products and active pharmaceutical ingredients. We present a highly enantioselective, inverse-electron-demand hetero-Diels-Alder reaction of olefins with in situ generated -Boc-formaldimine catalyzed by strong and confined Bro̷nsted acids. This transformation provides direct access to valuable 1,3-amino alcohols from styrenes and 1,1-disubtituted alkenes. Isotope labeling studies and kinetic analysis reveal an unusual mechanism involving an oxazinium intermediate and a catalyst order greater than one.