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Regio- and stereoselective cyclopropanation of unactivated alkenes under mild conditions remains a challenging yet fundamental transformation. We present a versatile palladium(II)-catalyzed method for the diastereoselective cyclopropanation of alkenyl amines and alkenyl acids, which leverages the nucleopalladation mechanism and the unique ambiphilic reactivity of sulfur ylides. This Pd(II)/Pd(IV) catalytic protocol selectively delivers anti- cyclopropanes for allylamines with a removable isoquinoline-1-carboxamide auxiliary, while enabling excellent syn -selectivity for alkenyl acid derivatives containing a 2-(aminomethyl)pyridine derivative as a directing group. The protocol is operationally simple and scalable, features a wide substrate generality, and also remains effective in the presence of various medicinally relevant scaffolds. The cyclopropane products were further transformed into 1,2,3-trifunctionalized cyclopropanes and engaged in an aza-Piancatelli reaction, introducing additional molecular complexity. DFT studies were performed to shed light on the reaction mechanism and the origins of the observed stereoselectivity.
Ballav et al. (Mon,) studied this question.