Divergent synthesis of chiral cyclic azides via asymmetric cycloaddition reactions of vinyl azides

Abstract

Vinyl azides, bearing conjugated azide and alkene functional groups, have been recognized as versatile building blocks in organic synthesis. In general vinyl azides act as 3-atom (CCN) synthons through the fast release of molecular nitrogen and have been extensively utilized in the construction of structurally diverse N-heterocycles. Keeping the azide moiety intact in organic transformations to synthesis chiral azides is an important but challenging task. Herein, we report an enantioselective copper(II)/BOX-catalyzed cycloaddition of vinyl azides, generating diverse chiral cyclic azides. α-Aryl substituted vinyl azides react with unsaturated keto esters through an inverse-electron-demand hetero-Diels-Alder reaction to afford chiral azido dihydropyrans with excellent enatioselectivities. In contrast, cyclohexenyl azides undergo a diastereo- and enantio-selective Diels-Alder reaction giving important azido octahydronaphthalenes with three continuous stereogenic centers. Notable features of these reactions include a very broad scope, mild reaction conditions and 100% atom economy.

Fig. 1

Reactivities of vinyl azides. a General reactivity of vinyl azides as CCN synthon driven by the release of N₂. b Cycloaddition reactivity of vinyl azides with azide retention (this work). c Selected important natural sesquiterpenoids with decalin motif

Fig. 2

Further synthetic applications of chiral cyclic azides and absolute configuration determination. a Click reaction of chiral cyclic azide 3a and the crystal structure of triazole 5. b Transformations of 3a into 6, 7, and 8. c Click reaction of chiral bicyclic azide 4a. d Reduction of 4a into trans-decalone (10)