美国加州理工学院Gregory C. Fu研究团队近日取得一项新成果。经过不懈努力，他们的最新研究提出了配体协同作用下的光诱导铜催化不对称酰胺化反应。该研究于2021年6月28日发表于国际一流学术期刊《自然》杂志上。
本文描述了一种利用普遍存在的含氮官能团——酰胺，通过基于铜(一种丰富的金属)的光诱导催化剂体系，实现对映收敛取代未活化外消旋烷基亲电试剂的方法。不对称N-烷基化的过程依赖于三种不同的配体：双膦、酚氧化合物和手性二胺，它们在原位组装一个铜/双膦/酚氧复合物作为光催化剂，以及一个手性铜/二胺复合物催化对映选择性C-N键的形成。
本研究将烷基亲电试剂的对映选择性N取代从活性亲电试剂（在被取代的碳上至少有一个sp或sp2杂化取代基的亲电试剂）拓展到非活性亲电试剂。
据了解，亲核试剂取代烷基亲电试剂是有机化学中的基础反应，实现高效、收敛的有机分子合成。近年来，尽管在开发过渡金属催化使用亲核碳试剂的亲核取代反应方面取得了重大进展，而在与亲核氮试剂的相应反应方面进展有限。此外，对于许多取代反应，键的构建本身并不是唯一的挑战，因为需要同时控制立体化学。
附：英文原文
Title: Photoinduced copper-catalysed asymmetric amidation via ligand cooperativity
Author: Caiyou Chen, Jonas C. Peters, Gregory C. Fu
Issue&Volume: 2021-06-28
Abstract: The substitution of an alkyl electrophile by a nucleophile is a foundational reaction in organic chemistry that enables the efficient and convergent synthesis of organic molecules. Whereas substantial progress has been reported in recent years in exploiting transition-metal catalysis to dramatically expand the scope of nucleophilic substitution reactions using carbon nucleophiles1–4, there has been limited progress in corresponding reactions with nitrogen nucleophiles5–8. Furthermore, for many substitution reactions, the bond construction itself is not the only challenge, as there is a need to control stereochemistry at the same time. Here we describe a method for the enantioconvergent substitution of unactivated racemic alkyl electrophiles by a ubiquitous nitrogen-containing functional group, an amide, through the use of a photoinduced catalyst system based on copper, an earth-abundant metal. This process for asymmetric N-alkylation relies upon three distinct ligands: a bisphosphine, a phenoxide and a chiral diamine, that assemble, in situ, a copper/bisphosphine/phenoxide complex that serves as a photocatalyst and a chiral copper/diamine complex that catalyzes enantioselective C–N bond formation. This study thus expands enantioselective N-substitution by alkyl electrophiles beyond activated electrophiles (those bearing at least one sp- or sp2-hybridized substituent on the carbon undergoing substitution)8–13 to include unactivated electrophiles.
DOI: 10.1038/s41586-021-03730-w
Source: https://www.nature.com/articles/s41586-021-03730-w