Mechanism and Origin of MAD-Induced Ni/NHC Catalyzed Regio- and Enantioselective C-H Cyclization of Pyridines with Alkenes

Chemistry : a European Journal
Xia ZhaoDongju Zhang

Abstract

This work presents a DFT-based computational study on the regio- and enantioselective C - H functionalization of pyridines with alkenes at the relatively unreactive C4-position, which was successfully achieved by Shi et al. [ J. Am. Chem. Soc. 2019 , 141 , 5628-5634] using Ni(0)/N-heterocyclic carbene (NHC) catalysis under the assistance of an aluminum-based Lewis acid additive (2,6-t-Bu 2 -4-Me-C 6 H 2 O) 2 AlMe (MAD). The calculations indicate that the selective functionalization involves a three-step mechanism where a unique H-migration assisted oxidation metalation (HMAOM) step is identified as the rate- and enantioselectivity-determining step. The newly proposed mechanism can well rationalize the experimental observation that the preferred product is the endo -type (vs exo -type), R -configuration (vs S -configuraton) product at the C4 (vs C2) position, and also unveil the reasons that the NHC ligand and the MAD additive can facilitate the reaction.

References

Jul 19, 2003·Pharmacological Reviews·Michael W N Deininger, Brian J Druker
Sep 30, 2005·Natural Product Reports·Joseph P Michael
Nov 4, 2005·Drugs·Tracy Swainston Harrison, Lesley J Scott
Sep 10, 2010·Chemistry : a European Journal·Matthew D Hill
Jan 11, 2012·Journal of the American Chemical Society·Yuta FujiwaraPhil S Baran
Apr 24, 2012·Nature Chemistry·Ryan J FelixMichel R Gagné
Aug 2, 2012·Organic & Biomolecular Chemistry·Balagopal S ShaibuRai-Shung Liu
Jan 12, 2013·Angewandte Chemie·Kiran Matcha, Andrey P Antonchick
Oct 9, 2014·Chemistry : a European Journal·Cuihuan GengChengbu Liu
Oct 11, 2014·Chemical Reviews·Christophe AllaisThierry Constantieux
Jan 27, 2017·Chemical Reviews·Zhe DongGuangbin Dong
Apr 27, 2017·Chemical Reviews·Kei MurakamiKenichiro Itami
Mar 16, 2018·Journal of the American Chemical Society·Johannes DieselNicolai Cramer
Apr 12, 2018·Journal of the American Chemical Society·Yin-Xia WangMengchun Ye
Jul 20, 2018·Journal of the American Chemical Society·Simon GrélaudJohn F Bower

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cell Migration

Cell migration is involved in a variety of physiological and pathological processes such as embryonic development, cancer metastasis, blood vessel formation and remoulding, tissue regeneration, immune surveillance and inflammation. Here is the latest research.

Related Papers

Angewandte Chemie
Magnus Rueping, Andrey P Antonchick
Mental Health Today
Yasmin MillerRichard Bentall
South Dakota Medicine : the Journal of the South Dakota State Medical Association
Tony L Berg
© 2021 Meta ULC. All rights reserved