Carbon–heteroatom bonds (C–X) are ubiquitous and are among the most reactive components of organic compounds. Therefore investigations of the construction of C–X bonds are fundamental and vibrant ...fields in organic chemistry. Transition-metal-catalyzed heteroatom–hydrogen bond (X–H) insertions via a metal carbene or carbenoid intermediate represent one of the most efficient approaches to form C–X bonds. Because of the availability of substrates, neutral and mild reaction conditions, and high reactivity of these transformations, researchers have widely applied transition-metal-catalyzed X–H insertions in organic synthesis. Researchers have developed a variety of rhodium-catalyzed asymmetric C–H insertion reactions with high to excellent enantioselectivities for a wide range of substrates. However, at the time that we launched our research, very few highly enantioselective X–H insertions had been documented primarily because of a lack of efficient chiral catalysts and indistinct insertion mechanisms. In this Account, we describe our recent studies of copper- and iron-catalyzed asymmetric X–H insertion reactions by using chiral spiro-bisoxazoline and diimine ligands. The copper complexes of chiral spiro-bisoxazoline ligands proved to be highly enantioselective catalysts for N–H insertions of α-diazoesters into anilines, O–H insertions of α-diazoesters into phenols and water, O–H insertions of α-diazophosphonates into alcohols, and S–H insertions of α-diazoesters into mercaptans. The iron complexes of chiral spiro-bisoxazoline ligands afforded the O–H insertion of α-diazoesters into alcohols and water with unprecedented enantioselectivities. The copper complexes of chiral spiro-diimine ligands exhibited excellent reactivity and enantioselectivity in the Si–H insertion of α-diazoacetates into a wide range of silanes. These transition-metal-catalyzed X–H insertions have many potential applications in organic synthesis because the insertion products, including chiral α-aminoesters, α-hydroxyesters, α-hydroxyphosphonates, α-mercaptoesters, and α-silyl esters, are important building blocks for the synthesis of biologically active compounds. The electronic properties of α-diazoesters and anilines markedly affected the enantioselectivity of N–H insertion reaction, which supports a stepwise ylide insertion mechanism. A novel binuclear spiro copper complex was isolated and fully characterized using X-ray diffraction analysis and ESI-MS analysis. The positive nonlinear effect indicated that binuclear copper complexes were the catalytically active species. The 14-electron copper centers, trans coordination model, perfect C 2-symmetric chiral pocket, and Cu–Cu interaction facilitate the performance of the chiral spiro catalysts in X–H insertion reactions.
Chiral carboxylic acid moieties are widely found in pharmaceuticals, agrochemicals, flavors, fragrances, and health supplements. Although they can be synthesized straightforwardly by ...transition-metal-catalyzed enantioselective hydrogenation of unsaturated carboxylic acids, because the existing chiral catalysts have various disadvantages, the development of new chiral catalysts with high activity and enantioselectivity is an important, long-standing challenge. Ruthenium complexes with chiral diphosphine ligands and rhodium complexes with chiral monodentate or bidentate phosphorus ligands have been the predominant catalysts for asymmetric hydrogenation of unsaturated acids. However, the efficiency of these catalysts is highly substrate-dependent, and most of the reported catalysts require a high loading, high hydrogen pressure, or long reaction time for satisfactory results. Our recent studies have revealed that chiral iridium complexes with chiral spiro-phosphine-oxazoline ligands and chiral spiro-phosphine-benzylamine ligands exhibit excellent activity and enantioselectivity in the hydrogenation of α,β-unsaturated carboxylic acids, including α,β-disubstituted acrylic acids, trisubstituted acrylic acids, α-substituted acrylic acids, and heterocyclic α,β-unsaturated acids. On the basis of an understanding of the role of the carboxy group in iridium-catalyzed asymmetric hydrogenation reactions, we developed a carboxy-group-directed strategy for asymmetric hydrogenation of olefins. Using this strategy, we hydrogenated several challenging olefin substrates, such as β,γ-unsaturated carboxylic acids, 1,1-diarylethenes, 1,1-dialkylethenes, and 1-alkyl styrenes in high yield and with excellent enantioselectivity. All these iridium-catalyzed asymmetric hydrogenation reactions feature high turnover numbers (up to 10000) and turnover frequencies (up to 6000 h–1), excellent enantioselectivities (greater than 95% ee with few exceptions), low hydrogen pressure (<12 atm), and operational simplicity. These features make chiral iridium catalysts superior or comparable to well-established chiral ruthenium and rhodium catalysts for asymmetric hydrogenation of unsaturated carboxylic acids. A number of chiral natural products and pharmaceuticals have been prepared by concise routes involving an iridium-catalyzed asymmetric hydrogenation of an unsaturated carboxylic acid as a key step. As part of a mechanistic study of iridium-catalyzed asymmetric hydrogenation of unsaturated acids, we isolated, for the first time, the migratory insertion intermediate in the iridium-catalyzed asymmetric hydrogenation of olefins, and this result strongly supports the involvement of an Ir(III)/Ir(V) catalytic cycle. The rigid, bulky scaffold of the chiral spiro-P,N-ligands of the catalysts not only prevents them from undergoing deactivating aggregation under the hydrogenation conditions but also is responsible for the efficient chiral induction. The carboxy group of the substrate acts as an anchor to ensure coordination of the substrate to the iridium center of the catalyst during the reaction and makes the hydrogenation proceed smoothly.
Transition-metal-catalysed carbene insertion reaction is a straightforward and efficient protocol for the construction of carbon-carbon or carbon-heteroatom bonds. Compared to the intensively studied ...and well-established "common" carbene insertion reactions, including carbene insertion into C-H, Si-H, N-H, O-H, and S-H bonds, several "uncommon" carbene insertion reactions, including carbene insertion into B-H, Sn-H, Ge-H, P-H, F-H, C-C, and M-M bonds, have been neglected for a long time. However, more and more studies on uncommon carbene insertion reactions have been disclosed recently, and clearly demonstrate the great synthetic potential of these reactions. The current perspective reviews the history and the newest advances of uncommon carbene insertion reactions, discusses their potential applications and challenges, and also presents an outlook of this promising field.
Transition-metal-catalysed carbene insertion reaction is a straightforward and efficient protocol for the construction of carbon-carbon or carbon-heteroatom bonds.
Our recently studies on three types of reactions with hydrogen transfer as a key step, including catalytic asymmetric proton transfer reactions using “chiral proton transfer shuttle”, catalytic B—H ...bond insertion containing a hydrogen atom transfer, and iron‐catalyzed hydrosilylation reactions containing hydride transfer were briefly introduced.
What is the most favorite and original chemistry developed in your research group?
The discovery of B—H bond insertion reaction.
How do you get into this specific field? Could you please share some experiences with our readers?
The reaction of B—H bond insertion was a serendipitous result during we pursuing the other carbene insertion reactions. My lesson on this project is that the discovery may come from bold hypothesis, cautious verification, and appropriate evaluation on unexpected results.
How do you supervise your students?
Try my best to stimulate their enthusiasm for innovation, provide them strongest supports, and explore unknown with them as a partner.
What is the most important personality for scientific research?
Passion for self‐actualization and curiosity.
How do you keep balance between research and family?
Travel with my family regularly and try to share my research progresses with them.
The studies from hydrogen transfer prospect enabled us to coin a concept of “chiral proton transfer shuttle”, find a set of B—H bond insertion reactions, and develop Fe catalysts for hydrosilylation.
The authors examine the enantioselective hydrogenation of enamines and imines in metal-catalyzed transitions. The enantioselective hydrogenation of several catalysts is also studied.
Transition metal-catalyzed carbene insertion into X-H bonds (X = N, O, S, and C) represents a typical carbene transfer reaction and has been widely used in organic synthesis. The ...enantioselectivity-determining step in some of these insertion reactions is the proton transfer of active intermediates such as ylides, metal enolates, or free enols. Since most of the traditional chiral transition metal catalysts tend to dissociate from these active intermediates and cannot be involved in the proton-transfer step, enantiocontrol of these insertion reactions has long been a challenging task. Since 2011, we have developed chiral spiro phosphoric acids as chiral proton-transfer shuttle (CPTS) catalysts, which have been proven to be efficient catalysts for the proton transfer of active intermediates in carbene insertion reactions. Upon combining with achiral dirhodium catalysts, the CPTS catalysts accomplish highly enantioselective insertions of N-H, S-H, and C-H bonds. Herein, a number of important chiral building blocks, including α-amino acid derivatives, α-amino ketones, α-thioesters, and α,α-diaryl acetates, were prepared with high yields and high enantioselectivities through these insertion reactions.
The development of chiral proton-transfer shuttles provides a totally new enantiocontrol strategy for transition metal-catalyzed asymmetric carbene insertion reactions.
Geminal bis(silanes) are versatile synthetic building blocks owing to their stability and propensity to undergo a variety of transformations. However, the scarcity of catalytic methods for their ...synthesis limits their structural diversity and thus their utility for further applications. Herein we report a new method for synthesis of geminal bis(silanes) by means of iron-catalyzed dihydrosilylation of alkynes. Iron catalysts were distinctly superior to the other tested catalysts, which clearly demonstrates that novel reactivity can be found by using iron catalysts. This method features 100% atom economy, regiospecificity, mild reaction conditions, and readily available starting materials. Using this method, we prepared a new type of geminal bis(silane) with secondary silane moieties, the Si–H bonds of which can easily undergo various transformations, facilitating the synthetic applications of these compounds. Preliminary mechanistic studies demonstrated that the reaction proceeds via two iron-catalyzed hydrosilylation reactions, the first generating β-(E)-vinylsilanes and the second producing geminal bis(silanes).
Herein, we report the development of a method for highly regio‐, stereo‐, and enantioselective B−H bond insertion reactions of α‐silylcarbenes generated from 1‐silylcyclopropenes in the presence of a ...chiral copper(I)/bisoxazoline catalyst for the construction of chiral γ,γ‐disubstituted allylic gem‐silylboranes, which cannot be prepared by any other known methods. This reaction is the first highly enantioselective carbene insertion reaction of α‐silylcarbenes ever to be reported. The method shows general applicability for various 3,3‐disubstituted silylcyclopropenes and exclusively affords E‐products. The novel chiral γ,γ‐disubstituted allylic gem‐silylborane products are versatile allylic bimetallic reagents with high stability and have great synthetic potential, especially for the construction of complex molecules with continuous chiral centers.
We developed a highly regio‐, stereo‐, and enantioselective CuI‐catalyzed ring‐opening/B−H bond insertion reaction between 1‐silylcyclopropenes and borane adducts, which represents the first highly enantioselective carbene insertion reaction of α‐silylcarbenes, and enriches the accesses and type of chiral gem‐bimetallic reagents.
Although iron-promoted diazo transformations were only discovered during the 1990s,iron can undergo facile changes in its oxidation state and possesses distinct Lewis acid character,and these ...properties have aforded iron a privileged position as a catalyst in the transformations of diazo compounds.In this review,we have provided an overview of the iron-catalyzed diazo transformation reactions reported in the literature by the end of 2013 with the aim of stimulating further interest in this area of research.
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