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Open accessJournal ArticleDOI: 10.1021/JACS.1C01929

Kinetic Resolution of Allyltriflamides through a Pd-Catalyzed C-H Functionalization with Allenes: Asymmetric Assembly of Tetrahydropyridines

02 Mar 2021-Journal of the American Chemical Society (American Chemical Society)-Vol. 143, Iss: 10, pp 3747-3752
Abstract: Enantioenriched, six-membered azacycles are essential structural motifs in many products of pharmaceutical or agrochemical interest. Here we report a simple and practical method for enantioselective assembly of tetrahydropyridines, which is paired to a kinetic resolution of α-branched allyltriflamides. The reaction consists of a formal (4+2) cycloaddition between the allylamine derivatives and allenes and is initiated by a palladium(II)-catalyzed C-H activation process. Both the chiral allylamide precursors and the tetrahydropyridine adducts were successfully obtained in high yields, with excellent enantioselectivity (up to 99% ee) and selectivity values of up to 127.

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8 results found

Journal ArticleDOI: 10.1039/D1CC02836G
Hui-Qi Ni1, Phillippa Cooper1, Keary M. Engle1Institutions (1)
Abstract: Palladium has proven to be effective in catalyzing the (hetero)annulation of CC bonds with ambiphilic organo(pseudo)halides. Through the employment of appropriate ambiphilic coupling partners, efficient annulation of a variety of allenes, 1,3-dienes, strained alkenes, styrenes, and other CC bond variants can be achieved to provide direct access to numerous useful hetero- and carbocyclic scaffolds. In this Feature Article, we summarize palladium-catalyzed (hetero)annulation methods reported since 2005 (spanning just over 15 years) and discuss outstanding challenges in this area of study.

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Topics: Annulation (61%)

1 Citations

Journal ArticleDOI: 10.1021/ACS.ORGLETT.1C02398
Ruxia Mao1, Yanliang Zhao2, Xiaohan Zhu1, Fen Wang1  +3 moreInstitutions (2)
03 Sep 2021-Organic Letters
Abstract: Enantioenriched allenes are important building blocks. While they have been accessed by other coupling methodologies, enantioenriched allenes have been rarely obtained via C-H activation. In this work, kinetic resolution of tertiary propargyl alcohols as an allenylating reagent has been realized via rhodium(III)-catalyzed C-H allenylation of benzamides. The reaction proceeded efficiently under mild conditions, and both the allenylated products and the propargyl alcohols were obtained in high enantioselectivities with an s-factor of up to 139. The resolution results from bias of the two propargylic substituents and is assisted by a chiral zinc carboxylate additive.

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Topics: Kinetic resolution (57%), Propargyl (55%), Carboxylate (53%)

Journal ArticleDOI: 10.1021/ACS.JOC.1C01143
Tao Liu, Lingli Han, Jing Zhang, Gang Lu1Institutions (1)
Abstract: Density functional theory calculations were performed to study the competing pathways of rhodacycle intermediates generated in Rh(III)-catalyzed annulations of 2-alkenyl phenols and 2-alkenyl anilides with alkynes. The results show that the multiple pathways of eight-membered rhodacycles can be subtly tuned to give specific cyclic products. The seven-membered oxacyclic and spirocyclic products from 2-alkenyl phenols are formed by favoring the pathway of dissociating the Rh-O bond of O-contained rhodacycles, which are followed by antarafacial nucleophilic attack. The indoline product from 2-alkenyl anilides is generated through the pathway of intramolecular olefin migratory insertion of the N-contained rhodacycle.

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Topics: Migratory insertion (55%), Indoline (54%), Intramolecular force (51%) ... read more


40 results found

Open accessJournal ArticleDOI: 10.1021/AR200185G
Abstract: Reactions that convert carbon–hydrogen (C–H) bonds into carbon–carbon (C–C) or carbon–heteroatom (C–Y) bonds are attractive tools for organic chemists, potentially expediting the synthesis of target molecules through new disconnections in retrosynthetic analysis. Despite extensive inorganic and organometallic study of the insertion of homogeneous metal species into unactivated C–H bonds, practical applications of this technology in organic chemistry are still rare. Only in the past decade have metal-catalyzed C–H functionalization reactions become more widely utilized in organic synthesis.Research in the area of homogeneous transition metal–catalyzed C–H functionalization can be broadly grouped into two subfields. They reflect different approaches and goals and thus have different challenges and opportunities. One approach involves reactions of completely unfunctionalized aromatic and aliphatic hydrocarbons, which we refer to as “first functionalization”. Here the substrates are nonpolar and hydrophobic a...

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Topics: Retrosynthetic analysis (51%)

2,097 Citations

Journal ArticleDOI: 10.1039/B816707A
Ramesh Giri1, Bing-Feng Shi2, Keary M. Engle2, Nathan Maugel3  +1 moreInstitutions (3)
Abstract: This critical review discusses historical and contemporary research in the field of transition metal-catalyzed carbon–hydrogen (C–H) bond activation through the lens of stereoselectivity. Research concerning both diastereoselectivity and enantioselectivity in C–H activation processes is examined, and the application of concepts in this area for the development of novel carbon–carbon and carbon–heteroatom bond-forming reactions is described. Throughout this review, an emphasis is placed on reactions that are (or may soon become) relevant in the realm of organic synthesis (221 references).

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1,173 Citations

Open accessJournal ArticleDOI: 10.1039/C6CS00075D
Abstract: Organic reactions that involve the direct functionalization of non-activated C–H bonds represent an attractive class of transformations which maximize atom- and step-economy, and simplify chemical synthesis. Due to the high stability of C–H bonds, these processes, however, have most often required harsh reaction conditions, which has drastically limited their use as tools for the synthesis of complex organic molecules. Following the increased understanding of mechanistic aspects of C–H activation gained over recent years, great strides have been taken to design and develop new protocols that proceed efficiently under mild conditions and duly benefit from improved functional group tolerance and selectivity. In this review, we present the current state of the art in this field and detail C–H activation transformations reported since 2011 that proceed either at or below ambient temperature, in the absence of strongly acidic or basic additives or without strong oxidants. Furthermore, by identifying and discussing the major strategies that have led to these improvements, we hope that this review will serve as a useful conceptual overview and inspire the next generation of mild C–H transformations.

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1,126 Citations

Open accessJournal ArticleDOI: 10.1021/ACS.CHEMREV.6B00692
17 Feb 2017-Chemical Reviews
Abstract: The development of new methods for the direct functionalization of unactivated C–H bonds is ushering in a paradigm shift in the field of retrosynthetic analysis. In particular, the catalytic enantioselective functionalization of C–H bonds represents a highly atom- and step-economic approach toward the generation of structural complexity. However, as a result of their ubiquity and low reactivity, controlling both the chemo- and stereoselectivity of such processes constitutes a significant challenge. Herein we comprehensively review all asymmetric transition-metal-catalyzed methodologies that are believed to proceed via an inner-sphere-type mechanism, with an emphasis on the nature of stereochemistry generation. Our analysis serves to document the considerable and rapid progress within in the field, while also highlighting limitations of current methods.

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Topics: Retrosynthetic analysis (52%)

463 Citations