Ni-Catalyzed Iterative Alkyl Transfer from Nitrogen Enabled by the In Situ Methylation of Tertiary Amines.

The Journal of Organic Chemistry
Chideraa Iheanyi NwachukwuAndrew George Roberts

Abstract

Current methods to achieve transition-metal-catalyzed alkyl carbon-nitrogen (C-N) bond cleavage require the preformation of ammonium, pyridinium, or sulfonamide derivatives from the corresponding alkyl amines. These activated substrates permit C-N bond cleavage, and their resultant intermediates can be intercepted to affect carbon-carbon bond-forming transforms. Here, we report the combination of in situ amine methylation and Ni-catalyzed benzalkyl C-N bond cleavage under reductive conditions. This method permits iterative alkyl group transfer from tertiary amines and demonstrates a deaminative strategy for the construction of Csp3-Csp3 bonds. We demonstrate PO(OMe)3 (trimethylphosphate) to be a Ni-compatible methylation reagent for the in situ conversion of trialkyl amines into tetraalkylammonium salts. Single, double, and triple benzalkyl group transfers can all be achieved from the appropriately substituted tertiary amines. Transformations developed herein proceed via recurring events: the in situ methylation of tertiary amines by PO(OMe)3, Ni-catalyzed C-N bond cleavage, and concurrent Csp3-Csp3 bond formation.

References

Jun 6, 2003·Journal of the American Chemical Society·Simon B Blakey, David W C MacMillan
Feb 17, 2005·Chemistry : a European Journal·Henri-Jean CristauMarc Taillefer
Oct 19, 2007·Angewandte Chemie·Eiji Tayama, Hiroshi Kimura
Mar 14, 2008·Chemical Communications : Chem Comm·Bing-Tao GuanZhang-Jie Shi
May 1, 1946·Journal of the American Chemical Society·D G THOMASC E DAVIS
Jul 19, 2011·Journal of the American Chemical Society·Mohammad MovassaghiStephen P Lathrop
Feb 15, 2012·The Journal of Organic Chemistry·Marco BlangettiDonal F O'Shea
Mar 23, 2013·Journal of Medicinal Chemistry·Dinakaran MurugesanIan H Gilbert
Aug 21, 2013·Journal of the American Chemical Society·Soumik Biswas, Daniel J Weix
Apr 2, 2014·Journal of the American Chemical Society·Mamoru TobisuNaoto Chatani
Jul 1, 2014·Organic Letters·Kazuyuki SatoAkira Ando
Aug 1, 2015·Journal of the American Chemical Society·Emily J TollefsonElizabeth R Jarvo
Oct 2, 2015·Chemical Reviews·Kunbing OuyangZhenfeng Xi
Oct 6, 2015·Chemistry : a European Journal·Hua ZhangKenichiro Itami
Jan 15, 2016·Chemical Society Reviews·Quanjun WangHanmin Huang
Mar 19, 2016·Angewandte Chemie·Toni MoragasRuben Martin
Oct 1, 2016·Nature Communications·Dong-Yu WangMasanobu Uchiyama
Oct 30, 2016·Chemistry : a European Journal·Gyurim ParkYoungmin You
Nov 5, 2016·Chemical Reviews·Vincent FroidevauxBernard Boutevin
Apr 1, 2017·Journal of the American Chemical Society·Corey H BaschMary P Watson
Apr 14, 2017·Journal of the American Chemical Society·Kelsey E PorembaSarah E Reisman
Apr 14, 2017·Journal of the American Chemical Society·Brian P WoodsAbigail G Doyle
Apr 18, 2017·The Journal of Organic Chemistry·Xiaodong ZouHongjian Lu
Apr 27, 2017·Journal of the American Chemical Society·Zhi-Chao Cao, Zhang-Jie Shi
Aug 2, 2017·Angewandte Chemie·Felix J R KlauckFrank Glorius
Aug 31, 2017·Chemical Communications : Chem Comm·Jiawang WangHegui Gong
Jan 6, 2018·The Journal of Organic Chemistry·Zhiguo ZhangLei Shi
Aug 10, 2018·Journal of the American Chemical Society·Jingjing WuVarinder K Aggarwal
Dec 7, 2018·Journal of the American Chemical Society·Li-Li LiaoDa-Gang Yu
Jan 27, 2019·Journal of the American Chemical Society·Shane PlunkettMary P Watson
Aug 1, 2019·Journal of the American Chemical Society·Rong-De HeXing-Zhong Shu

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Citations

May 14, 2021·Nature·Sean H KennedyMark D Levin

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