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Anti-Selective [3+2] (Hetero)annulation of Non-Conjugated Alkenes via Directed Nucleopalladation

preprint
submitted on 19.06.2020 and posted on 22.06.2020 by Hui-Qi Ni, Ilia Kevlishvili, Pranali Bedekar, Joyann Barber, Shouliang Yang, Michelle Tran-Dubé, Hou-Xiang Lu, Indrawan McAlpine, Peng Liu, Keary Engle
2,3-Dihydrobenzofurans and indolines are common substructures in medicines and natural products. Herein, we describe a method that enables direct access to these core structures from non-conjugated alkenyl amides and ortho-iodoanilines/phenols. Under palladium(II) catalysis this [3+2] heteroannulation proceeds in an anti-selective fashion and tolerates a wide variety of functional groups. N-Acetyl, -tosyl, and -alkyl substituted ortho-iodoanilines, as well as free –NH2 variants, are all effective. Preliminary results with carbon-based coupling partners also demonstrate the viability of forming indane core structures using this approach. Experimental and computational data with phenols support a mechanism involving turnover-limiting, endergonic directed oxypalladation, followed by intramolecular oxidative addition and reductive elimination.

Funding

5R35GM125052-03

1R35GM128779

Alfred P. Sloan Fellowship

Camille Dreyfus Teacher-Scholar Program

Cottrell Scholars Program

History

Email Address of Submitting Author

keary@scripps.edu

Institution

The Scripps Research Institute

Country

USA

ORCID For Submitting Author

0000-0003-2767-6556

Declaration of Conflict of Interest

No conflict of interest to declare.

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