α-Fluoro-α-nitro(phenylsulfonyl)methane as a fluoromethyl pronucleophile: Efficient stereoselective Michael addition to chalcones

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 106; no. 11; pp. 4090 - 4094
• Main Authors: Prakash, G.K. Surya, Wang, Fang, Stewart, Timothy, Mathew, Thomas, Olah, George A
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 17-03-2009; National Acad Sciences
• Subjects: Addition reactions; Alcohols; Biochemistry; Catalysts; Chalcones - chemistry; Chalconoids; Chemical bases; Fluorine; Hydrocarbons, Fluorinated - chemistry; Ketones; Physical Sciences; Solvents; Stereoisomerism; Sulfones
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0900179106

Highly efficient stereoselective 1,4-addition of racemic α-fluoro-α-nitro(phenylsulfonyl)methane (FNSM) as a fluoromethyl pronucleophile to α,β-unsaturated ketones using a wide range of chiral organobifunctional catalysts under moderate conditions in the absence of an additional base has been achieved. A series of catalysts was screened for the enantioselective addition of FNSM to chalcones and the catalysts CN I, CD I, QN I-IV, and QD I were found to enable this reaction, successfully providing exclusive 1,4-addition products stereoselectively in high yields (conversion, diastereomeric ratio, and enantiomeric excess). Studies involving a model reaction and systematic analysis of the absolute configuration support the suggested mechanism.