Enantioselective Synthesis of Secondary β-Trifluoromethyl Alcohols via Catalytic Asymmetric Reductive Trifluoroalkylation and Diastereoselective Reduction
Bing-Bing Wu, Jie Xu, Kang-Jie Bian, Qian Gao and Xi-Sheng Wang*
*Department of Chemistry, University of Science and
Technology of China, Hefei, Anhui 230026, China, Email: xswang77
ustc.edu.cn
B.-B. Wu, J. Xu, K.-J. Bian, Q. Gao, X.-S. Wang, J. Am. Chem. Soc., 2022, 144, 6543-6550.
DOI: 10.1021/jacs.2c01422
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Abstract
A nickel-catalyzed asymmetric reductive cross-coupling trifluoroalkylation of acyl chlorides enables an enantioselective synthesis of α-trifluoromethylated ketones. A one-pot reduction furnished alcohols bearing β-CF3-substituted stereogenic carbons with excellent diastereoselectivity. The reactions offer high yields/enantioselectivity, mild conditions, and good functional group compatibility.
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Details
The article discusses the enantioselective synthesis of secondary β-trifluoromethyl alcohols via a novel nickel-catalyzed asymmetric reductive trifluoroalkylation of acyl chlorides. This method addresses the challenge of constructing β-trifluoromethylated alcohols with adjacent stereocenters, which are important in drug development due to their unique biological properties. The process involves the initial formation of chiral α-trifluoromethylated ketones, followed by a one-pot reduction to yield the desired alcohols with high diastereoselectivity and enantioselective retention. The method demonstrates high yields, mild conditions, and good functional group compatibility, making it suitable for late-stage trifluoroalkylation of complex biologically active molecules. The study highlights the potential of this approach for the efficient synthesis of CF3-containing chiral drugs, offering a powerful tool for pharmaceutical research and development. The authors optimized reaction conditions, including the use of various chiral ligands and solvents, to achieve excellent enantioselectivity and yield. This work provides a significant advancement in the field of asymmetric synthesis, enabling the production of diverse enantioenriched β-trifluoromethyl alcohols for potential therapeutic applications.
Key Words
α-trifluoromethyl carbonyl compounds, β-trifluoromethyl alcohols, manganese, sodium borohydride
ID: J48-Y2022
