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

烯烃与原位生成的N-Boc-甲醛亚胺的催化不对称环加成反应

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Abstract

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 N-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.

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