Palladium-catalyzed Suzuki–Miyaura cross-coupling or aryl halides is widely employed in the synthesis of many important molecules in synthetic chemistry, including pharmaceuticals, polymers and functional materials. Herein, we disclose the first palladium-catalyzed decarbonylative Suzuki–Miyaura cross-coupling of amides for the synthesis of biaryls through the selective activation of the N–C(O) bond of amides. This new method relies on the precise sequence engineering of the catalytic cycle, wherein decarbonylation occurs prior to the transmetallation step. The reaction is compatible with a wide range of boronic acids and amides, providing valuable biaryls in high yields (>60 examples). DFT studies support a mechanism involving oxidative addition, decarbonylation and transmetallation and provide insight into high N–C(O) bond activation selectivity. Most crucially, the reaction establishes the use of palladium catalysis in the biaryl Suzuki–Miyaura cross-coupling of the amide bond and should enable the design of a wide variety of cross-coupling methods in which palladium rivals the traditional biaryl synthesis from aryl halides and pseudohalides.
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Decarbonylative cross-coupling of amides
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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- Award ID(s):
- 1650766
- NSF-PAR ID:
- 10090801
- Date Published:
- Journal Name:
- Organic & Biomolecular Chemistry
- Volume:
- 16
- Issue:
- 43
- ISSN:
- 1477-0520
- Page Range / eLocation ID:
- 7998 to 8010
- 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/c8ob01832d
