Anti-selective [3+2] (Hetero)annulation of non-conjugated alkenes via directed nucleopalladation
Hui‐Qi Ni, Ilia Kevlishvili, Pranali G. Bedekar, Joyann S. Barber, Shouliang Yang, Michelle Tran‐Dubé, Andrew M. Romine, Hou‐Xiang Lu, Indrawan McAlpine, Peng Liu, Keary M. Engle
Abstract
Abstract 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 –NH 2 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.