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      Catalytic enantioselective C( sp 3)–H functionalization involving radical intermediates

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          Abstract

          Recently, with the boosted development of radical chemistry, enantioselective functionalization of C( sp 3)–H bonds via a radical pathway has witnessed a renaissance. In principle, two distinct catalytic modes, distinguished by the steps in which the stereochemistry is determined (the radical formation step or the radical functionalization step), can be devised. This Perspective discusses the state-of-the-art in the area of catalytic enantioselective C( sp 3)–H functionalization involving radical intermediates as well as future challenges and opportunities.

          Abstract

          Enantioselective functionalization of ubiquitous C(sp 3)–H bonds via radical species has witnessed a renaissance in the past years. Here, the authors summarize the main achievements in the field by identifying two main reaction pathways determining the stereochemistry and give an outlook on future challenges and opportunities.

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          Most cited references97

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          Merging photoredox catalysis with organocatalysis: the direct asymmetric alkylation of aldehydes.

          Photoredox catalysis and organocatalysis represent two powerful fields of molecule activation that have found widespread application in the areas of inorganic and organic chemistry, respectively. We merged these two catalysis fields to solve problems in asymmetric chemical synthesis. Specifically, the enantioselective intermolecular alpha-alkylation of aldehydes has been accomplished using an interwoven activation pathway that combines both the photoredox catalyst Ru(bpy)3Cl2 (where bpy is 2,2'-bipyridine) and an imidazolidinone organocatalyst. This broadly applicable, yet previously elusive, alkylation reaction is now highly enantioselective and operationally trivial.
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            Cross-dehydrogenative coupling (CDC): exploring C-C bond formations beyond functional group transformations.

            Synthetic chemists aspire both to develop novel chemical reactions and to improve reaction conditions to maximize resource efficiency, energy efficiency, product selectivity, operational simplicity, and environmental health and safety. Carbon-carbon bond formation is a central part of many chemical syntheses, and innovations in these types of reactions will profoundly improve overall synthetic efficiency. This Account describes our work over the past several years to form carbon-carbon bonds directly from two different C-H bonds under oxidative conditions, cross-dehydrogenative coupling (CDC). We have focused most of our efforts on carbon-carbon bonds formed via the functionalization of sp(3) C-H bonds with other C-H bonds. In the presence of simple and cheap catalysts such as copper and iron salts and oxidants such as hydrogen peroxide, dioxygen, tert-butylhydroperoxide, and 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ), we can directly functionalize various sp(3) C-H bonds by other C-H bonds without requiring preactivation. We demonstrate (1) reaction of alpha-C-H bonds of nitrogen in amines, (2) reaction of alpha-C-H bonds of oxygen in ethers, (3) reaction of allylic and benzylic C-H bonds, and (4) reaction of alkane C-H bonds. These CDC reactions can tolerate a variety of functional groups, and some can occur under aqueous conditions. Depending on the specific transformation, we propose the in situ generation of different intermediates. These methods provide an alternative to the separate steps of prefunctionalization and defunctionalization that have traditionally been part of synthetic design. As a result, these methods will increase synthetic efficiencies at the most fundamental level. On an intellectual level, the development of C-C bond formations based on the reaction of only C-H bonds (possibly in water) challenges us to rethink some of the most fundamental concepts and theories regarding chemical reactivities. A successful reaction requires the conventionally and theoretically less reactive C-H bonds to react selectively in the presence of a variety of functional groups. With further investigation, we expect that C-C bond formations based on cross-dehydrogenative coupling will have a positive economic and ecological impact on the next generation of chemical syntheses.
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              The Cross-Dehydrogenative Coupling of C sp 3H Bonds: A Versatile Strategy for CC Bond Formations

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                Author and article information

                Contributors
                guqs@sustech.edu.cn
                liuxy3@sustech.edu.cn
                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Publishing Group UK (London )
                2041-1723
                20 January 2021
                20 January 2021
                2021
                : 12
                : 475
                Affiliations
                [1 ]GRID grid.263817.9, Shenzhen Grubbs Institute and Department of Chemistry, Guangdong Provincial Key Laboratory of Catalysis, , Southern University of Science and Technology, ; 518055 Shenzhen, China
                [2 ]GRID grid.263817.9, Academy for Advanced Interdisciplinary Studies and Department of Chemistry, , Southern University of Science and Technology, ; 518055 Shenzhen, China
                Author information
                http://orcid.org/0000-0002-3840-425X
                http://orcid.org/0000-0002-6978-6465
                Article
                20770
                10.1038/s41467-020-20770-4
                7817665
                33473126
                bbbebcb6-47ac-4296-9347-dbeae016eb3d
                © The Author(s) 2021

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 14 October 2020
                : 18 December 2020
                Funding
                Funded by: FundRef https://doi.org/10.13039/501100001809, National Natural Science Foundation of China (National Science Foundation of China);
                Award ID: 22001109
                Award ID: 22025103
                Award ID: 21831002
                Award Recipient :
                Funded by: Guangdong Basic and Applied Basic Research Foundation (No. 2019A1515110822)
                Funded by: Guangdong Provincial Key Laboratory of Catalysis (No. 2020B121201002) Guangdong Innovative Program (No. 2019BT02Y335) SUSTech Special Fund for the Construction of High-Level Universities (No. G02216303)
                Categories
                Perspective
                Custom metadata
                © The Author(s) 2021

                Uncategorized
                asymmetric catalysis,stereochemistry,synthetic chemistry methodology
                Uncategorized
                asymmetric catalysis, stereochemistry, synthetic chemistry methodology

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