Merging Electron Transfer with 1,2‐Metalate Rearrangement: Deoxygenative Arylation of Aromatic Amides with Arylboronic Esters

Jiao, Jiwen; Wang, Xiaoming

doi:10.1002/ange.202104359

Cited by 6 publications

(1 citation statement)

References 110 publications

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“…This is the case of the reductive alkylation of amides, an indispensable transformation for the synthesis of many biologically active alkaloids (6)(7)(8)(9)(10)(11)(12). During the past decade, considerable advancements on the direct transformations of amides have been achieved (14)(15)(16)(17)(18) either via the electrophilic activation of amides (19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31) or via catalytic partial reduction of amides (32)(33)(34)(35)(36)(37)(38)(39)(40). However, very few examples of the asymmetric transformations of amides have been reported (41)(42)(43)(44), and those involving the catalytic asymmetric reductive transformation of the amide group itself is even more scarce (42,43).…”

Section: Introductionmentioning

confidence: 99%

Multicatalysis protocol enables direct and versatile enantioselective reductive transformations of secondary amides

Chen

Shao

et al. 2022

Sci. Adv.

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The catalytic asymmetric geminal bis-nucleophilic addition to nonreactive functional groups is a type of highly desirable yet challenging transformation in organic chemistry. Here, we report the first catalytic asymmetric reductive/deoxygenative alkynylation of secondary amides. The method is based on a multicatalysis strategy that merges iridium/copper relay catalysis with organocatalysis. A further combination with the palladium-catalyzed alkyne hydrogenation allows the one-pot enantioselective reductive alkylation of secondary amides. This versatile protocol allows the efficient synthesis of four types of α-branched chiral amines, which are prevalent structural motifs of active pharmaceutical ingredients. The protocol also features excellent enantioselectivity, chemoselectivity, and functional group tolerance to be compatible with more reactive functional groups such as ketone and aldehyde. The synthetic utility of the method was further demonstrated by the late-stage functionalization of two drug derivatives and the concise, first catalytic asymmetric approach to the κ-opioid antagonist aticaprant.

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Section: Introductionmentioning

confidence: 99%

Multicatalysis protocol enables direct and versatile enantioselective reductive transformations of secondary amides

Chen

Shao

et al. 2022

Sci. Adv.

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Deoxygenative Cross‐Coupling of Aromatic Amides with Polyfluoroarenes

Wang

et al. 2022

Angewandte Chemie

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Considering the ubiquitous nature and ready synthesis of amides, and the great significance of organofluorine‐containing species, the cross‐coupling of amides and polyfluoroarenes, leading to new carbon–carbon bond‐forming methodologies, would find useful applications in synthesis, late‐stage functionalization, and rapid generation of molecular diversity. Herein, we present a novel synthesis of α‐polyfluoroaryl amines via Sm/SmI2‐mediated deoxygenative cross‐coupling of aromatic amides with polyfluoroarenes through direct C−H functionalization. The structural and functional diversity of these readily available precursors provides a versatile and flexible strategy for the streamlined synthesis of α‐polyfluoroaryl amines. Combining experimental and theoretical studies, a novel plausible mechanism of the α‐aminocarbene‐mediated C−H insertion has been revealed, which may stimulate future work for the development of novel methods in amine synthesis.

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Challenges and Breakthroughs in Selective Amide Activation

2022

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In contrast to ketones and carboxylic esters, amides are classically seen as comparatively unreactive members of the carbonyl family, owing to their unique structural and electronic features. However, recent decades have seen the emergence of research programmes focused on the selective activation of amides under mild conditions. In the past four years, this area has continued to rapidly develop, with new advances coming in at a fast pace. Several novel activation strategies have been demonstrated as effective tools for selective amide activation, enabling transformations that are at once synthetically useful and mechanistically intriguing. This Minireview comprises recent advances in the field, highlighting new trends and breakthroughs in what could be called a new age of amide activation.

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Merging Electron Transfer with 1,2‐Metalate Rearrangement: Deoxygenative Arylation of Aromatic Amides with Arylboronic Esters

Cited by 6 publications

References 110 publications

Multicatalysis protocol enables direct and versatile enantioselective reductive transformations of secondary amides

Multicatalysis protocol enables direct and versatile enantioselective reductive transformations of secondary amides

Deoxygenative Cross‐Coupling of Aromatic Amides with Polyfluoroarenes

Challenges and Breakthroughs in Selective Amide Activation

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