Pd-catalyzed halocyclizations of unactivated 1,6-diynes through a formal anti-carbopalladation/bromide radical cascade

We report a Pd-catalyzed halocyclization of unactivated 1,6-diynes with N-bromosuccinimide (NBS). This approach produces stereo-defined dibromo substituted dihydropyrans, tetrahydropyridines, and 3-methylene cyclohexenes with exocyclic double bond appendages in mostly good yields. Copper salt was found to be a useful Lewis acid in this reaction. Mechanistically, a formal anti-carbopalladation and a bromide radical promoted Pd-II-Pd-III-Pd-I-Pd-II catalytic cycles were proposed to be involved in the formation of the dibromo-substituted products. Further functionalization of the dihydropyran derivatives underwent B(C6F5)(3)-catalyzed ring opening, and reduction afforded dibrominated 1,3-dienes with excellent stereoselectivity. (C) 2021 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. Published by Elsevier B.V. All rights reserved.

Automated summary

The Pd-catalyzed halocyclization of unactivated 1,6-diynes with N-bromosuccinimide results in stereo-defined dibromo substituted dihydropyrans, tetrahydropyridines, and 3-methylene cyclohexenes with exocyclic double bond appendages in mostly good yields. Copper salt serves as a useful Lewis acid in this reaction. Mechanistically, a formal anti-carbopalladation and a bromide radical promoted Pd-II-Pd-III-Pd-I-Pd-II catalytic cycles are proposed to be involved in the formation of the dibromo-substituted products.