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Highly Efficient and Stereoselective Julia–Kocienski Protocol for the Synthesis of α‐Fluoro‐α,β‐unsaturated Esters and Weinreb Amides Employing 3,5‐Bis(trifluoromethyl)phenyl (BTFP) Sulfones
Author(s) -
Alonso Diego A.,
Fuensanta Mónica,
GómezBengoa Enrique,
Nájera Carmen
Publication year - 2008
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.200800194
Subject(s) - chemistry , trifluoromethyl , sulfonyl , stereoselectivity , amide , dimethylformamide , catalysis , organic chemistry , potassium carbonate , combinatorial chemistry , medicinal chemistry , solvent , alkyl
α‐Fluoroacetates 3 and Weinreb amide 4 , bearing a α‐[3,5‐bis(trifluoromethyl)phenyl]sulfonyl (BTFP‐sulfonyl) group at the α‐position, are employed in the highly stereoselective synthesis of α‐fluoro‐α,β‐unsaturated alkenoates and Weinreb amides, respectively. Aromatic and aliphatic aldehydes are condensed under extremely mild and simple reaction conditions using potassium carbonate in dimethylformamide at room temperature under solid‐liquid phase‐transfer catalysis conditions in good yields and high Z ‐diastereoselectivities, specially in the case of the fluorinated Weinreb amides. A detailed computational mechanistic study suggests a final non‐concerted elimination of sulfur dioxide and 3,5‐bis(trifluoromethyl)phenoxide and explains the observed high stereoselectivities for the reaction on the basis of thermodynamic and kinetic considerations.