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CO2-Mediated Pd-Catalyzed Stereo- and Regioselective Arylation of Free Allylamines

preprint
revised on 03.06.2020 and posted on 04.06.2020 by Vinod Landge, Justin Maxwell, Pratibha Chand-Thakuri, Mohit Kapoor, Evan Diemler, Michael Young
Mizoroki-Heck couplings are a powerful method for elaborating alkene feedstocks. While selective functionalization of terminal olefins has been achieved by catalyst design, selective functionalization of internal olefins has generally required use of directing groups except in the case of Michael acceptors. Allylamine substrates have typically required protection to be suitable for these reactions, decreasing the step and atom economy of these procedures. Herein we demonstrate that the addition of CO2 (dry ice) allows for the reproducible stereospecific arylation of both secondary and primary allylamines in the presence of a PdII catalyst. Notably, the product 3,3’-diarylallylamine motif is prevalent in a variety of biologically-relevant structures, and this method represents the most straightforward synthesis of these targets to date. Key features of the method are the ability to access relatively mild conditions that facilitate a broad substrate scope, as well as direct diarylation of terminal allylamine substrates. In addition, several complex and therapeutically-relevant molecules are included to demonstrate the utility of the transformation. Mechanistic studies point to an amine-directed reaction where CO2 serves to protect the substrate and product from degradation.

Funding

ACS Herman Frasch Foundation (830-HF17), Start-up from The University of Toledo. ETD thanks The University of Toledo - Office of Undergraduate Research for an USRCAP Fellowship in support of this work.

History

Email Address of Submitting Author

michael.young8@utoledo.edu

Institution

The University of Toledo

Country

United States

ORCID For Submitting Author

0000-0002-3256-5562

Declaration of Conflict of Interest

US20190185392

Version Notes

V3 Has dramatically altered the understanding of the chemistry.

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