Balhara Reena, Chatterjee Ritwika, Jindal Garima
Department of Organic Chemistry, Indian Institute of Science, Bengaluru-560012, Karnataka, India.
Chem Soc Rev. 2024 Nov 12;53(22):11004-11044. doi: 10.1039/d4cs00742e.
Constructing highly proficient C-X (X = O, N, S, ) and C-C bonds by leveraging TMs (transition metals) (Fe, Cu, Pd, Rh, Au, ) and enzymes to catalyze carbene insertion into X-H/C(sp)-H is a highly versatile strategy. This is primarily achieved through the generation of metal carbenes from the interaction of TMs with diazo compounds. Over the last few decades, significant advancements have been made, encompassing a wide array of X-H bond insertions using various TMs. These reactions typically favor a stepwise ionic pathway where the nucleophilic attack on the metal carbene leads to the generation of a metal ylide species. This intermediate marks a critical juncture in the reaction cascade, presenting multiple avenues for proton transfer to yield the X-H inserted product. The mechanism of C(sp)-H insertion reactions closely resembles those of X-H insertion reactions and thus have been included here. A major development in carbene insertion reactions has been the use of engineered enzymes as catalysts. Since the seminal report of a non-natural "carbene transferase" by Arnold in 2013, "P411", several heme-based enzymes have been reported in the literature to catalyze various abiological carbene insertion reactions into C(sp)-H, N-H and S-H bonds. These enzymes possess an extraordinary ability to regulate the orientation and conformations of reactive intermediates, facilitating stereoselective carbene transfers. However, the absence of a suitable stereochemical model has impeded the development of asymmetric reactions employing a lone chiral catalyst, including enzymes. There is a pressing need to investigate alternative mechanisms and models to enhance our comprehension of stereoselectivity in these processes, which will be crucial for advancing the fields of asymmetric synthesis and biocatalysis. The current review aims to provide details on the mechanistic aspects of the asymmetric X-H and C(sp)-H insertion reactions catalyzed by Fe, Cu, Pd, Rh, Au, and enzymes, focusing on the detailed mechanism and stereochemical model. The review is divided into sections focusing on a specific X-H/C(sp)-H bond type catalyzed by different TMs and enzymes.
利用过渡金属（TMs）（铁、铜、钯、铑、金等）和酶催化卡宾插入X-H/C(sp)-H以构建高度熟练的C-X（X = O、N、S等）和C-C键是一种非常通用的策略。这主要是通过TMs与重氮化合物相互作用生成金属卡宾来实现的。在过去几十年中，已经取得了重大进展，包括使用各种TMs进行的一系列X-H键插入反应。这些反应通常倾向于逐步离子途径，其中对金属卡宾的亲核攻击导致生成金属叶立德物种。这个中间体是反应级联中的一个关键节点，为质子转移提供了多种途径以生成X-H插入产物。C(sp)-H插入反应的机制与X-H插入反应非常相似，因此也包含在此处。卡宾插入反应的一个主要进展是使用工程酶作为催化剂。自2013年阿诺德报道非天然“卡宾转移酶”“P411”以来，文献中已报道了几种基于血红素的酶催化各种非生物卡宾插入C(sp)-H、N-H和S-H键的反应。这些酶具有非凡的能力来调节反应中间体的取向和构象，促进立体选择性卡宾转移。然而，缺乏合适的立体化学模型阻碍了使用单一手性催化剂（包括酶）的不对称反应的发展。迫切需要研究替代机制和模型，以增强我们对这些过程中立体选择性的理解，这对于推进不对称合成和生物催化领域至关重要。本综述旨在详细介绍由铁、铜、钯、铑、金和酶催化的不对称X-H和C(sp)-H插入反应的机理方面，重点关注详细机制和立体化学模型。综述分为几个部分，重点介绍由不同TMs和酶催化的特定X-H/C(sp)-H键类型。
