Decarbonylative borylation of carboxylic acids is reported. Carbon electrophiles are generated directly after reagent‐enabled decarbonylation of the in situ accessible sterically‐hindered acyl derivative of a carboxylic acid under catalyst controlled conditions. The scope and the potential impact of this method are demonstrated in the selective borylation of a variety of aromatics (>50 examples). This strategy was used in the late‐stage derivatization of pharmaceuticals and natural products. Computations reveal the mechanistic details of the unprecedented C−O bond activation of carboxylic acids. By circumventing the challenging decarboxylation, this strategy provides a general synthetic platform to access arylpalladium species for a wide array of bond formations from abundant carboxylic acids. The study shows a powerful combination of experiment and computation to predict decarbonylation selectivity.
- Award ID(s):
- 1650766
- PAR ID:
- 10090790
- Date Published:
- Journal Name:
- Organic Chemistry Frontiers
- Volume:
- 5
- Issue:
- 16
- ISSN:
- 2052-4129
- Page Range / eLocation ID:
- 2515 to 2521
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Abstract Decarbonylative borylation of carboxylic acids is reported. Carbon electrophiles are generated directly after reagent‐enabled decarbonylation of the in situ accessible sterically‐hindered acyl derivative of a carboxylic acid under catalyst controlled conditions. The scope and the potential impact of this method are demonstrated in the selective borylation of a variety of aromatics (>50 examples). This strategy was used in the late‐stage derivatization of pharmaceuticals and natural products. Computations reveal the mechanistic details of the unprecedented C−O bond activation of carboxylic acids. By circumventing the challenging decarboxylation, this strategy provides a general synthetic platform to access arylpalladium species for a wide array of bond formations from abundant carboxylic acids. The study shows a powerful combination of experiment and computation to predict decarbonylation selectivity.
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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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Abstract Cooperative bimetallic catalysis is a fundamental approach in modern synthetic chemistry. We report bimetallic cooperative catalysis for the direct decarbonylative heteroarylation of ubiquitous carboxylic acids via acyl C‐O/C‐H coupling. This novel catalytic system exploits the cooperative action of a copper catalyst and a palladium catalyst in decarbonylation, which enables highly chemoselective synthesis of important heterobiaryl motifs through the coupling of carboxylic acids with heteroarenes in the absence of prefunctionalization or directing groups. This cooperative decarbonylative method uses common carboxylic acids and shows a remarkably broad substrate scope (>70 examples), including late‐stage modification of pharmaceuticals and streamlined synthesis of bioactive agents. Extensive mechanistic and computational studies were conducted to gain insight into the mechanism of the reaction. The key step involves intersection of the two catalytic cycles via transmetallation of the copper–aryl species with the palladium(II) intermediate generated by oxidative addition/decarbonylation.
- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1039/C8QO00585K
