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. 2009 Mar 17;106(11):4090-4.
doi: 10.1073/pnas.0900179106. Epub 2009 Feb 23.

Alpha-fluoro-alpha-nitro(phenylsulfonyl)methane as a fluoromethyl pronucleophile: efficient stereoselective Michael addition to chalcones

G K Surya Prakash  1 , Fang Wang, Timothy Stewart, Thomas Mathew, George A Olah
Affiliations

Alpha-fluoro-alpha-nitro(phenylsulfonyl)methane as a fluoromethyl pronucleophile: efficient stereoselective Michael addition to chalcones

G K Surya Prakash et al. Proc Natl Acad Sci U S A. .

Abstract

Highly efficient stereoselective 1,4-addition of racemic alpha-fluoro-alpha-nitro(phenylsulfonyl)methane (FNSM) as a fluoromethyl pronucleophile to alpha,beta-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.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Scheme 1.
Scheme 1.
Mitsunobu reaction of alcohols with 1-fluoro-bis(phenylsulfonyl)methane.
Scheme 2.
Scheme 2.
Michael addition of FSM derivatives to α,β-unsaturated compounds.
Fig. 1.
Fig. 1.
Cinchona-based bifunctional chiral catalysts screened for enantioselective 1,4-addition of α-fluoro-α-nitro(phenylsulfonyl)methane [FNSM (1)] to chalcone.
Scheme 3.
Scheme 3.
Enantioselective 1,4-addition of α-fluoro-α-nitro-(phenylsulfonyl)methane (FNSM) to chalcones.
Fig. 2.
Fig. 2.
Formation of α-fluoro-α-nitro(phenylsulfonyl)methide anion and suggested transition state involving chalcone-QN I assembly during Michael addition.
Scheme 4.
Scheme 4.
1,4-Addition of α-fluoro-α-nitro(phenylsulfonyl)methane (FNSM) to methyl vinyl ketone with the bifunctional catalyst QN I.
Fig. 3.
Fig. 3.
Crystal structure of (3R,4R)-4-fluoro-4-nitro-1,3-diphenyl-4-(phenylsulfonyl)butan-1-one (3a).
See this image and copyright information in PMC

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