Dataset Information

Copper-Catalyzed Regio- and Enantioselective Hydroboration of Difluoroalkyl-Substituted Internal Alkenes.

ABSTRACT: Catalytic asymmetric hydroboration of fluoroalkyl-substituted alkenes is a straightforward approach to access chiral small molecules possessing both fluorine and boron atoms. However, enantioselective hydroboration of fluoroalkyl-substituted alkenes without fluorine elimination has been a long-standing challenge in this field. Herein, a copper-catalyzed hydroboration of difluoroalkyl-substituted internal alkenes with high levels of regio- and enantioselectivities is reported. The native carbonyl directing group, copper hydride system, and bisphosphine ligand play crucial roles in suppressing the undesired fluoride elimination. This atom-economic protocol provides a practical synthetic platform to obtain a wide scope of enantioenriched secondary boronates bearing the difluoromethylene moieties under mild conditions. Synthetic applications including functionalization of biorelevant molecules, versatile functional group interconversions, and preparation of difluoroalkylated Terfenadine derivative are also demonstrated.

SUBMITTER: Zhao TQ

PROVIDER: S-EPMC10724385 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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Copper-Catalyzed Regio- and Enantioselective Hydroboration of Difluoroalkyl-Substituted Internal Alkenes.

Zhao Tao-Qian TQ Xu Hui H Tian Yu-Chen YC Tang Xiaodong X Dang Yanfeng Y Ge Shaozhong S Ma Jun-An JA Zhang Fa-Guang FG

Advanced science (Weinheim, Baden-Wurttemberg, Germany) 20231025 35

Catalytic asymmetric hydroboration of fluoroalkyl-substituted alkenes is a straightforward approach to access chiral small molecules possessing both fluorine and boron atoms. However, enantioselective hydroboration of fluoroalkyl-substituted alkenes without fluorine elimination has been a long-standing challenge in this field. Herein, a copper-catalyzed hydroboration of difluoroalkyl-substituted internal alkenes with high levels of regio- and enantioselectivities is reported. The native carbonyl ...[more]

PMID: 37880870

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Project description:Mechanistic studies of the copper-catalyzed asymmetric hydroboration of vinylarenes and internal alkenes are reported. Catalytic systems with both DTBM-SEGPHOS and SEGPHOS as the ligands have been investigated. With DTBM-SEGPHOS as the ligand, the resting state of the catalyst, which is also a catalytic intermediate, for hydroboration of 4-fluorostyrene is a phenethylcopper(I) complex ligated by the bisphosphine. This complex was fully characterized by NMR spectroscopy and X-ray crystallography. The turnover-limiting step in the catalytic cycle for the reaction of vinylarenes is the borylation of this phenethylcopper complex with pinacolborane (HBpin) to form the boronate ester product and a copper hydride. Experiments showed that the borylation occurs with retention of configuration at the benzylic position. β-Hydrogen elimination and insertion of the alkene to reform this phenethylcopper complex is reversible in the absence of HBpin but is irreversible during the catalytic process because reaction with HBpin is faster than β-hydrogen elimination of the phenethylcopper complex. Studies on the hydroboration of a representative internal alkene, trans-3-hexenyl 2,4,6-trichlorobenzoate, which undergoes enantio- and regioselective addition of HBpin catalyzed by DTBM-SEGPHOS, KOtBu, and CuCl, also was conducted, and these studies revealed that a DTBM-SEGPHOS-ligated copper(I) dihydridoborate complex is the resting state of the catalyst in this case. The turnover-limiting step in the catalytic cycle for hydroboration of the internal alkene is insertion of the alkene into a copper(I) hydride formed by reversible dissociation of HBpin from the copper dihydridoborate species. With SEGPHOS as the ligand, a dimeric copper hydride was observed as the dominant species during the hydroboration of 4-fluorostyrene, and this complex is not catalytically competent. DFT calculations provide a view into the origins of regio- and enantioselectivity of the catalytic process and indicate that the charge on the copper-bound carbon and delocalization of charge onto the aryl ring control the rate of the alkene insertion and the regioselectivity of the catalytic reactions of vinylarenes.

Dataset Information

Copper-Catalyzed Regio- and Enantioselective Hydroboration of Difluoroalkyl-Substituted Internal Alkenes.

Publications

Copper-Catalyzed Regio- and Enantioselective Hydroboration of Difluoroalkyl-Substituted Internal Alkenes.

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