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Anhydrous and Stereoretentive Fluoride-Enhanced Suzuki-Miyaura Coupling of Immunomodulatory Imide Drug Derivatives.

ABSTRACT: Immunomodulatory imide drugs form the core of many pharmaceutically relevant structures, but C_sp²-C_sp² bond formation via metal-catalyzed cross coupling is difficult due to the sensitivity of the glutarimide ring ubiquitous in these structures. We report that replacement of the traditional alkali base with a fluoride source enhances a previously challenging Suzuki-Miyaura coupling on glutarimide-containing compounds with trifluoroborates. These enabling conditions are reactive enough to generate these derivatives in high yields but mild enough to preserve both the glutarimide and its sensitive stereocenter. Experimental and computational data suggest a mechanistically distinct process of π-coordination of the trifluoroborate enabled by these conditions.

SUBMITTER: Tracy WF

PROVIDER: S-EPMC11002932 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature

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Anhydrous and Stereoretentive Fluoride-Enhanced Suzuki-Miyaura Coupling of Immunomodulatory Imide Drug Derivatives.

Tracy William F WF Davies Geraint H M GHM Grant Lauren N LN Ganley Jacob M JM Moreno Jesus J Cherney Emily C EC Davies Huw M L HML

The Journal of organic chemistry 20240307 7

Immunomodulatory imide drugs form the core of many pharmaceutically relevant structures, but Csp2-Csp2 bond formation via metal-catalyzed cross coupling is difficult due to the sensitivity of the glutarimide ring ubiquitous in these structures. We report that replacement of the traditional alkali base with a fluoride source enhances a previously challenging Suzuki-Miyaura coupling on glutarimide-containing compounds with trifluoroborates. These enablin ...[more]

PMID: 38452367

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