Stereoselective Palladium-Catalyzed Carboetherification of Cyclopropenes via a Tethering Strategy

Abstract

Highly functionalized cyclopropanes are often sought after chemical motifs as building blocks in synthetic and medicinal chemistry. However, their stereoselective synthesis using catalytic methods remains a challenge. Herein we report the first carboetherification of cyclopropenes using a palladium-catalyzed tethering strategy. This reaction was compatible with various functional groups, and could be performed using aryl, alkynyl and vinyl coupling partners. The carboetherification proceeded in a stereoselective manner imparted by the trifluoromethylated tether and afforded pentasubstituted spirocyclopropanes as single diastereoisomers, extending significantly the scope of metal-catalyzed difunctionalization of strained alkenes. This process could be easily scaled up to a gram scale, and product modifications were enabled either by acid mediated ring-opening or by accessing free alcohols and amines.