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Cross-coupling reactions are among the most powerful C–C and C–X bond forming tools in organic chemistry. Traditionally, cross-coupling methods rely on the use of aryl halides or pseudohalides as electrophiles. In the past three years, decarbonylative cross-couplings of amides have emerged as an attractive method for the construction of a wide variety of carbon–carbon and carbon–heteroatom bonds, allowing for the synthetically-valuable functional group inter-conversion of the amide bond. These previously elusive reactions hinge upon selective activation of the N–C(O) acyl amide bond, followed by CO extrusion, in a formal double N–C/C–C bond activation, to generate a versatile aryl–metal intermediate as an attractive alternative to traditional cross-couplings of aryl halides and pseudohalides. In this perspective review, we present recent advances and key developments in the field of decarbonylative cross-coupling reactions of amides as well as discuss future challenges and potential applications for this exciting field.
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Decarbonylative Sonogashira cross-coupling: a fruitful marriage of alkynes with carboxylic acid electrophiles
The Sonogashira cross-coupling is one of the most fundamental C–C bond-forming reactions, wherein the strategic value of an alkyne moiety has found widespread applications at the frontiers of organic chemistry, materials science and drug discovery as the cornerstone building block of chemical synthesis. Although traditional variants of Sonogashira cross-coupling involve aryl halides and pseudohalides as electrophiles, recently, tremendous advances have been made in the unconventional disconnection exploiting common carboxylic acids by a decarbonylation/transmetalation pathway. This manifold (1) permits one to take advantage of carboxylic acids as a ubiquitous class of substrates in organic synthesis that are derived from an orthogonal pool of precursors to aryl halides and pseudohalides and (2) combines the benefits of the palladium-catalyzed C(sp 2 )–C(sp) coupling of terminal alkynes with the inherent presence of the carboxylic acid moiety in pharmaceuticals, natural products and organic materials. In this highlight article, we summarize the recent progress in the decarbonylative Sonogashira cross-coupling of carboxylic acid electrophiles to produce arylalkynes and conjugated enynes as a novel avenue for chemical synthesis, whereby a large number of chemical reactions critically rely on transformations of alkynes.
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- Award ID(s):
- 1650766
- PAR ID:
- 10323821
- Date Published:
- Journal Name:
- Organic Chemistry Frontiers
- Volume:
- 9
- Issue:
- 1
- ISSN:
- 2052-4129
- Page Range / eLocation ID:
- 216 to 222
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1039/D1QO01539G
