Molecular editing of aza-arene C–H bonds by distance, geometry and chirality

Fan, Zhoulong; Chen, Xiangyang; Tanaka, Keita; Park, Han Seul; Lam, Nelson Y. S.; Wong, Jonathan J.; Houk, K. N.; Yu, Jin‐Quan

doi:10.1038/s41586-022-05175-1

Cited by 71 publications

(39 citation statements)

References 34 publications

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“…On the basis of steric control, iridium-catalyzed C-H borylation and silylation reactions occur regioselectively at the meta position (16)(17)(18)(19)(20)(21). Palladium-catalyzed meta-C-H olefination and arylation reactions were pioneered by the Yu group by using designed ligands for regiose-lectivity control (22)(23)(24)(25). Despite the extensive development and application of those transition metal-catalyzed reactions, the reaction type and scope are still limited; for example, 3-substituted pyridines are required for regioselectivity control in most cases (15).…”

mentioning

confidence: 99%

Radical and ionic meta -C–H functionalization of pyridines, quinolines, and isoquinolines

Cao

Cheng

Studer

2022

Science

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Carbon-hydrogen (C−H) functionalization of pyridines is a powerful tool for the rapid construction and derivatization of many agrochemicals, pharmaceuticals, and materials. Because of the inherent electronic properties of pyridines, selective meta -C−H functionalization is challenging. Here, we present a protocol for highly regioselective meta -C−H trifluoromethylation, perfluoroalkylation, chlorination, bromination, iodination, nitration, sulfanylation, and selenylation of pyridines through a redox-neutral dearomatization-rearomatization process. The introduced dearomative activation mode provides a diversification platform for meta-selective reactions on pyridines and other azaarenes through radical as well as ionic pathways. The broad scope and high selectivity of these catalyst-free reactions render these processes applicable for late-stage functionalization of drugs.

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mentioning

confidence: 99%

Radical and ionic meta -C–H functionalization of pyridines, quinolines, and isoquinolines

Cao

Cheng

Studer

2022

Science

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“…For instance, Yu recently reported the C3–C7 selective functionalization of bicyclic aza-arenes via directing templates or ligands with distinctive designs. 6 This report in combination with those of others on complementary methods 5 now fully establishes a unified late-stage ‘molecular editing’ strategy to directly modify the quinoline ring at any given site in various orders. Despite the remarkable achievements made so far, this field is still in its infancy.…”

mentioning

confidence: 63%

Chemo- and regioselective synthesis of C3-sulfonate esters and C4-chlorides of quinolines under metal-free conditions

Chen

Liu

et al. 2023

Org. Chem. Front.

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“…Selectivity is one of the crucial pursuits in direct C–H functionalization. To distinguish different C–H bonds in organic molecules and achieve site-selective functionalization, directing group and directing template strategies have been proved powerful in transition-metal catalysis. To further improve efficiency, reactions guided by inherent directing groups, transient directing groups, and transient mediators thrived later, enriching the chemical toolbox and facilitating organic synthesis.…”

Section: Introductionmentioning

confidence: 99%

Functionalized Cycloolefin Ligand as a Solution to Ortho-Constraint in the Catellani-Type Reaction

Wang

Jiao

2023

J. Am. Chem. Soc.

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The Catellani reaction, i.e., the Pd/norbornene (NBE) catalysis, has been evolved into a versatile approach to multisubstituted arenes via the ortho-functionalization/ipso-termination process of a haloarene. Despite significant advances over the past 25 years, this reaction still suffered from an intrinsic limitation in the substitution pattern of haloarene, referred to as “ortho-constraint”. When an ortho substituent is absent, the substrate often fails to undergo an effective mono ortho-functionalization process, and either ortho-difunctionalization products or NBE-embedded byproducts predominate. To tackle this challenge, structurally modified NBEs (smNBEs) have been developed, which were proved effective for the mono ortho-aminative, -acylative, and -arylative Catellani reactions of ortho-unsubstituted haloarenes. However, this strategy is incompetent for solving the ortho-constraint in Catellani reactions with ortho-alkylation, and to date there lacks a general solution to this challenging but synthetically useful transformation. Recently, our group developed the Pd/olefin catalysis, in which an unstrained cycloolefin ligand served as a covalent catalytic module to enable the ortho-alkylative Catellani reaction without NBE. In this work, we show that this chemistry could afford a new solution to ortho-constraint in the Catellani reaction. A functionalized cycloolefin ligand bearing an amide group as the internal base was designed, which allowed for mono ortho-alkylative Catellani reaction of iodoarenes suffering from ortho-constraint before. Mechanistic study revealed that this ligand is capable of both accelerating the C–H activation and inhibiting side reactions, which accounts for its superior performance. The present work showcased the uniqueness of the Pd/olefin catalysis as well as the power of rational ligand design in metal catalysis.

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Molecular editing of aza-arene C–H bonds by distance, geometry and chirality

Cited by 71 publications

References 34 publications

Radical and ionic meta -C–H functionalization of pyridines, quinolines, and isoquinolines

Radical and ionic meta -C–H functionalization of pyridines, quinolines, and isoquinolines

Chemo- and regioselective synthesis of C3-sulfonate esters and C4-chlorides of quinolines under metal-free conditions

Functionalized Cycloolefin Ligand as a Solution to Ortho-Constraint in the Catellani-Type Reaction

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