Remote Construction of N‐Heterocycles via 1,4‐Palladium Shift‐Mediated Double C−H Activation
Takeru Miyakoshi, Nadja Niggli, Olivier Baudoin
Abstract
Abstract In the past years, Pd 0 ‐catalyzed C(sp 3 )−H activation provided efficient and step‐economical methods to synthesize carbo‐ and heterocycles via direct C(sp 2 )−C(sp 3 ) bond formation. We report herein that a 1,4‐Pd shift allows access to N‐heterocycles which are difficult to build via a direct reaction. It is shown that o ‐bromo‐ N ‐methylanilines undergo a 1,4‐Pd shift at the N ‐methyl group, followed by intramolecular trapping by C(sp 2 )−H or C(sp 3 )−H activation at another nitrogen substituent and remote C−C bond formation to generate biologically relevant isoindolines and β‐lactams. The product selectivity is influenced by the employed ligand, with NHCs favoring the product of remote C−C coupling against products arising from direct C−C coupling and N‐demethylation.