Catalytic enantioselective Michael addition of 1-fluorobis(phenylsulfonyl)methane to α,β-unsaturated ketones

ORGN 671

Tatsuya Furukawa,, Jumpei Kawazoe1, Shuichi Nakamura2, Norio Shibata,, and Takeshi Toru2. (1) Department of Frontier Materials, Graduate School of Engineering, Nagoya Institute of Technology, 19-628, Gokiso, Showa, Nagoya, 466-8555, Japan, (2) Department of Frontier Materials, Nagoya Institute of Technology, Gokiso, Showa-ku, Nagoya, 466-8555, Japan
There are high demands in both academia and industry for enantiopure fluorine-containing organic molecules because of their unique pharmacological properties. Compounds with monofluoromethyl groups are also important in biological systems. The current state-of-the-art asymmetric catalysis uses organocatalysts or ligand–metal complexes that allow access to the chiral monofluorinated organic compounds with high enantiocontrol. However, most of the recent innovations in this area are based on the enantioselective fluorination reactions developed by us and others. In comparison, the enantioselective fluoromethylation reactions still need to be investigated. We reported the FBSM-based catalytic enantioselective Mannich-type monofluoromethylation which provided chiral α-fluoromethylamines with excellent enantioselectivities. On the basis of this concept we used FBSM as a potential monofluoromethide equivalent, and report herein the first catalytic, asymmetric 1,4-conjugate addition of FBSM to α,β-unsaturated ketones. A wide substrate scope, a high level of enantioselectivity, and the flexibility to generate either enantiomer of the product have been achieved.