Accessing Unsymmetrically Linked Heterocycles through Stereoselective Palladium-Catalyzed Domino Cyclization

Ramon Arora; José F Rodríguez; Andrew Whyte; Mark Lautens

doi:10.1002/anie.202112288

Accessing Unsymmetrically Linked Heterocycles through Stereoselective Palladium-Catalyzed Domino Cyclization

Angew Chem Int Ed Engl. 2022 Jan 3;61(1):e202112288. doi: 10.1002/anie.202112288. Epub 2021 Nov 25.

Authors

Ramon Arora¹, José F Rodríguez¹, Andrew Whyte¹, Mark Lautens¹

Affiliation

¹ Davenport Research Laboratories, Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, Ontario, M5S 3H6, Canada.

PMID: 34739741
DOI: 10.1002/anie.202112288

Abstract

A palladium-catalyzed strategy is presented to synthesize unsymmetrically linked heterocycles within stereoselective tetrasubstituted olefins. This reaction is proposed to occur via a vinyl-Pd^II intermediate capable of initiating the cyclization of various alkyne-tethered nucleophiles. Products are formed in up to 96 % yield and excellent stereoselectivities are obtained using low catalyst loadings. This transformation was scalable up to 1 mmol and mechanistic studies suggest a syn-carbopalladation of the carbamoyl chloride followed by Pd^II -catalyzed cyclization of alkyne-tethered nucleophiles.

Keywords: cyclization; heterocycles; palladium; stereoselectivity; synthetic methods.

Publication types

Research Support, Non-U.S. Gov't

Abstract

Publication types

Grants and funding