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Abstract Aryl thioethers are tremendously important motifs in various facets of chemical science. Traditional technologies for the precise assembly of aryl thioethers rely on transition‐metal‐catalyzed cross‐coupling of aryl halides; however, despite the continuous advances, the scope of these methods remains limited. Recently a series of reports has advanced an alternative manifold in which thio(esters) are subject to transition‐metal‐catalyzed decarbonylation, which (1) permits to exploit ubiquitous carboxylic acids as highly desirable and orthogonal precursors to aryl halides; (2) overcomes the issues of high concentration of thiolate anion leading to catalyst poisoning; (3) enables for novel disconnections not easily available from aryl halides; and (4) introduces new concepts in catalysis.
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Control of Redox‐Active Ester Reactivity Enables a General Cross‐Electrophile Approach to Access Arylated Strained Rings**
Abstract Strained rings are increasingly important for the design of pharmaceutical candidates, but cross‐coupling of strained rings remains challenging. An attractive, but underdeveloped, approach to diverse functionalized carbocyclic and heterocyclic frameworks containing all‐carbon quaternary centers is the coupling of abundant strained‐ring carboxylic acids with abundant aryl halides. Herein we disclose the development of a nickel‐catalyzed cross‐electrophile approach that couples a variety of strained ringN‐hydroxyphthalimide (NHP) esters, derived from the carboxylic acid in one step, with various aryl and heteroaryl halides under reductive conditions. The chemistry is enabled by the discovery of methods to control NHP ester reactivity, by tuning the solvent or using modified NHP esters, and the discovery thatt‐BuBpyCamCN, an L2X ligand, avoids problematic side reactions. This method can be run in flow and in 96‐well plates.
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- Award ID(s):
- 1919350
- PAR ID:
- 10378533
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Angewandte Chemie International Edition
- Volume:
- 61
- Issue:
- 33
- ISSN:
- 1433-7851
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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