Work

Empowering Diastereoselective Cyclopropanation of Unactivated Alkenes with Sulfur Ylides through Nucleopalladation

Year: 2025

Type: article

Abstract: 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 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.

Source: Journal of the American Chemical Society

DOI: 10.1021/jacs.5c03146

Authors: Nityananda Ballav, Chandan Kumar Giri, Shib Nath Saha, Manoj V. Mane, Mahiuddin Baidya

Institutions: Indian Institute of Technology Madras, Jain University

Language: English

Topic: Cyclopropane Reaction Mechanisms

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: green