scispace - formally typeset
Open accessJournal ArticleDOI: 10.1039/D1SC00469G

NHC-catalyzed covalent activation of heteroatoms for enantioselective reactions

02 Mar 2021-Chemical Science (Royal Society of Chemistry (RSC))-Vol. 12, Iss: 14, pp 5037-5043
Abstract: Covalent activation of heteroatoms enabled by N-heterocyclic carbene (NHC) organic catalysts for enantioselective reactions is evaluated and summarized in this review. To date, sulfur, oxygen, and nitrogen atoms can be activated in this manner to react with another substrate to construct chiral carbon–heteroatom bonds with high optical enantioselectivities. The activation starts with addition of an NHC catalyst to the carbonyl moiety (aldehyde or imine) of substrates that contain heteroatoms. The key in this approach is the formation of intermediates covalently bound to the NHC catalyst, in which the heteroatom of the substrate is activated as a nucleophilic reactive site.

... read more

Topics: Heteroatom (56%), Imine (53%), Catalysis (52%) ... read more
Citations
  More

7 results found


Open accessJournal ArticleDOI: 10.1039/D1SC01910D
16 Jun 2021-Chemical Science
Abstract: N-Heterocyclic carbenes (NHCs) belong to the popular family of organocatalysts used in a wide range of reactions, including that for the synthesis of complex natural products and biologically active compounds. In their organocatalytic manifestation, NHCs are known to impart umpolung reactivity to aldehydes and ketones, which are then exploited in the generation of homoenolate, acyl anion, and enolate equivalents suitable for a plethora of reactions such as annulation, benzoin, Stetter, Claisen rearrangement, cycloaddition, and C–C and C–H bond functionalization reactions and so on. A common thread that runs through these NHC catalyzed reactions is the proposed involvement of an enaminol, also known as the Breslow intermediate, formed by the nucleophilic addition of an NHC to a carbonyl group of a suitable electrophile. In the emerging years of NHC catalysis, enaminol remained elusive and was largely considered a putative intermediate owing to the difficulties encountered in its isolation and characterization. However, in the last decade, synergistic efforts utilizing an array of computational and experimental techniques have helped in gaining important insights into the formation and characterization of Breslow intermediates. Computational studies have suggested that a direct 1,2-proton transfer within the initial zwitterionic intermediate, generated by the action of an NHC on the carbonyl carbon, is energetically prohibitive and hence the participation of other species capable of promoting an assisted proton transfer is more likely. The proton transfer assisted by additives (such as acids, bases, other species, or even a solvent) was found to ease the kinetics of formation of Breslow intermediates. These important details on the formation, in situ detection, isolation, and characterization of the Breslow intermediate are scattered over a series of reports spanning well over a decade, and we intend to consolidate them in this review and provide a critical assessment of these developments. Given the central role of the Breslow intermediate in organocatalytic reactions, this treatise is expected to serve as a valuable source of knowledge on the same.

... read more

Topics: Organocatalysis (52%), Umpolung (51%)

7 Citations


Open accessJournal ArticleDOI: 10.3390/CATAL11080972
14 Aug 2021-Catalysts
Abstract: N-Heterocyclic carbene (NHC) ligands have become a privileged structural motif in modern homogenous and heterogeneous catalysis. The last two decades have brought a plethora of structurally and electronically diversified carbene ligands, enabling the development of cutting-edge transformations, especially in the area of carbon-carbon bond formation. Although most of these were accomplished with common imidazolylidene and imidazolinylidene ligands, the most challenging ones were only accessible with the acenaphthylene-derived N-heterocyclic carbene ligands bearing a π-extended system. Their superior σ-donor capabilities with simultaneous ease of modification of the rigid backbone enhance the catalytic activity and stability of their transition metal complexes, which makes BIAN-NHC (BIAN—bis(imino)acenaphthene) ligands an attractive tool for the development of challenging reactions. The present review summarizes synthetic efforts towards BIAN-NHC metal complexes bearing acenaphthylene subunits and their applications in modern catalysis, with special emphasis put on recently developed enantioselective processes.

... read more

2 Citations


Journal ArticleDOI: 10.1039/D1QO01127H
Jian Gao1, Jie Feng1, Ding Du1Institutions (1)
Abstract: N-Heterocyclic carbene (NHC) organocatalysis has emerged as a powerful tool in the field of modern organic synthesis especially in asymmetric construction of various cyclic skeletons. As emerging NHC-bound nucleophilic intermediates, azolium dienolates have been widely investigated and applied in NHC-catalyzed transformations due to their unique reactivities and versatile structures. Particularly, four representative kinds of reactive azolium dienolates (I–IV) have been explored as versatile nucleophilic synthons via either α-functinalization or remote γ-functionalization to achieve efficient construction of complex skeletons. Moreover, these NHC-bound intermediates had wide-ranging applications in asymmetric synthesis of diversely enantioenriched centrally chiral molecules. In this review, the recent advances in NHC-catalyzed generation of azolium dienolates from different precursors and their applications in the synthesis of various valuable molecules are summarized comprehensively.

... read more

1 Citations


Open accessJournal ArticleDOI: 10.3390/CATAL11081013
22 Aug 2021-Catalysts
Abstract: Organocatalysts are abundantly used for various transformations, particularly to obtain highly enantio- and diastereomeric pure products by controlling the stereochemistry. These applications of organocatalysts have been the topic of several reviews. Organocatalysts have emerged as one of the very essential areas of research due to their mild reaction conditions, cost-effective nature, non-toxicity, and environmentally benign approach that obviates the need for transition metal catalysts and other toxic reagents. Various types of organocatalysts including amine catalysts, Bronsted acids, and Lewis bases such as N-heterocyclic carbene (NHC) catalysts, cinchona alkaloids, 4-dimethylaminopyridine (DMAP), and hydrogen bond-donating catalysts, have gained renewed interest because of their regioselectivity. In this review, we present recent advances in regiodivergent reactions that are governed by organocatalysts. Additionally, we briefly discuss the reaction pathways of achieving regiodivergent products by changes in conditions such as solvents, additives, or the temperature.

... read more


Journal ArticleDOI: 10.1021/ACS.ORGLETT.1C02676
Shuquan Wu1, Jun Xu2, Jun Xu1, Rui Deng1  +4 moreInstitutions (2)
17 Sep 2021-Organic Letters
Abstract: A carbene-catalyzed reaction to synthesize chiral dihydroisoquinolinones via an o-quinodimethane (o-QDM) intermediate is disclosed. o-QDM reacts with cyclic sulfonic imines via annulation to afford highly enantioenriched dihydroisoquinolinone products. ESI-HRMS studies suggest a stepwise Mannich addition and acylation reaction pathway, and the pathways of the catalytic and uncatalyzed background reactions are evaluated via DFT calculations.

... read more

Topics: Annulation (61%), Acylation (52%), Carbene (52%)

References
  More

66 results found


Journal ArticleDOI: 10.1038/NATURE13384
26 Jun 2014-Nature
Abstract: The successful isolation and characterization of an N-heterocyclic carbene in 1991 opened up a new class of organic compounds for investigation. From these beginnings as academic curiosities, N-heterocyclic carbenes today rank among the most powerful tools in organic chemistry, with numerous applications in commercially important processes. Here we provide a concise overview of N-heterocyclic carbenes in modern chemistry, summarizing their general properties and uses and highlighting how these features are being exploited in a selection of pioneering recent studies.

... read more

2,348 Citations


Journal ArticleDOI: 10.1021/CR068372Z
23 Oct 2007-Chemical Reviews
Abstract: In the investigation of efficient chemical transformations, the carbon-carbon bond-forming reactions play an outstanding role. In this context, organocatalytic processes have achieved considerable attention. 1 Beside their facile reaction course, selectivity, and environmental friendliness, new synthetic strategies are made possible. Particularly, the inversion of the classical reactivity (Umpolung) opens up new synthetic pathways. 2 In nature, the coenzyme thiamine (vitamin B1), a natural thiazolium salt, utilizes a catalytic variant of this concept in biochemical processes as nucleophilic acylations. 3 The catalytically active species is a nucleophilic carbene. 4

... read more

2,240 Citations



Journal ArticleDOI: 10.1039/C2CS15333E
Xavier Bugaut1, Xavier Bugaut2, Frank Glorius1Institutions (2)
Abstract: The umpolung strategy encompasses all the methods that make organic molecules react in an inverse manner compared to their innate polarity-driven reactivity. This concept entered the field of organocatalysis when it was recognized that N-heterocyclic carbenes (NHCs) can provide catalytic access to acyl anion equivalents. Since then, tremendous efforts have followed to develop a broad variety of NHC-catalyzed reactions. In addition to this, more recent research developments have shown that other families of organocatalysts are also able to mediate transformations in which inversion of polarity is involved. This tutorial review aims at offering a didactic overview of organocatalytic umpolung and should serve as an inspiration for further progress in this field.

... read more

Topics: Umpolung (57%)

916 Citations


Journal ArticleDOI: 10.1021/AR030050J
Dieter Enders1, Tim Balensiefer1Institutions (1)
Abstract: The coenzyme thiamine (vitamin B1), a natural thiazolium salt, is involved in many enzymatic catalyses. Since it has been proposed that the catalytically active species of these reactions is a nucleophilic carbene, many chemists have tried to perform enzyme mimetic asymmetric carbene catalysis. After a long and difficult search, stable carbenes are finally isolated, characterized, and in the chemist's hands. The experiments of decades have finally resulted in successful enantioselective benzoin condensations and enantioselective intramolecular Stetter reactions as important examples of carbene catalyzed asymmetric nucleophilic acylation processes.

... read more

Topics: Transition metal carbene complex (62%), Stetter reaction (61%), Benzoin condensation (58%) ... read more

878 Citations