Direct Amidination of Alkenes Via C–H Activation of Pyridinyl Formimidamide Synthon

Abstract Alkenes are among the most abundant and versatile feedstocks in synthetic chemistry, yet methods for their direct and regioselective conversion into nitrogen-containing frameworks remain scarce. In particular, the direct catalytic amidination of alkenes has remained underdeveloped. Herein, we report a rhodium-catalyzed anti-Markovnikov amidination of alkenes using a stable pyridinyl formimidamide synthon. This reaction enables the direct installation of amidine moieties onto a wide range of alkenes, including styrenes, aliphatic alkenes, and challenging internal alkenes that undergo efficient chain-walking with high regioselectivity and broad functional group tolerance, accommodating unprotected amines, phenols, and halides. The resulting pyridyl amidines can be readily transformed into amides, carboxylic acids and esters, establishing a practical platform for alkene diversification. Notably, late-stage functionalization of complex bioactive molecules, including cyclosporine A, FK506, and quinine etc., provides access to previously inaccessible analogues. Mechanistic investigations, highlighted by the crystallographic capture of a key rhodium–aminopyridinyl formimidamide intermediate, provide compelling evidence for the proposed catalytic cycle. Collectively, this work not only fills a critical gap in alkene functionalization but also offers a concise and general route to high-value nitrogen-containing architectures.