Synergy of activating substrate and introducing C-H···O interaction to achieve Rh2(II)-catalyzed asymmetric cycloisomerization of 1,n-enynes

Abstract

We report the first Rh2(II)-catalyzed asymmetric cycloisomerization of activated enynes to provide cyclopropane-fused tetrahydropyridines in good yields and excellent enantioselectivities under mild conditions. The activated group, CHZ (Z is electron-withdrawing group (EWG)), in the enyne substrates exerts two synergetic roles, one is to activate alkyne for the cyclopropanation reaction; the other is to introduce the C–H···O interaction between substrate and catalyst (reducing the energy barrier of the reaction). This double-mode activation was supported by both density functional theory (DFT) calculations and experimental tests. This strategy was also extended to other CH2Z (Z can be OH, OMe, F) as activating groups that made the CH2 more acidic so that the substrates could also form increased C–H···O interaction with the catalyst.