Anti-selective [3+2] (Hetero)annulation of non-conjugated alkenes via directed nucleopalladation

• DOI: 10.1038/s41467-020-20182-4
• Publication Date: 2020-12-22T11:03:02Z
• Authors: Hui-Qi Ni; Ilia Kevlishvili; Pranali G. Bedekar; Joyann S. Barber; Shouliang Yang; Michelle Tran-Dubé; Andrew M. Romine; Hou-Xiang Lu; Indrawan J. McAlpine; Peng Liu; Keary M. Engle
• Keywords: Aniline Compounds; Science; Q; Alkenes; 01 natural sciences; Article; 3. Good health; 0104 chemical sciences; Phenols; Thermodynamics; Computer Simulation; Palladium

Abstract2,3-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 studies on reactions with phenols support a mechanism involving turnover-limiting, endergonic directed oxypalladation, followed by intramolecular oxidative addition and reductive elimination.