3,5‐Bis(trifluoromethyl)phenyl Sulfones for the Highly Stereoselective Julia–Kocienski Synthesis of α,β‐Unsaturated Esters and Weinreb Amides

The 3,5‐bis(trifluoromethyl)phenyl (BTFP) sulfones tert ‐butyl α‐(BTFPsulfonyl)acetate ( 4 ) and Weinreb α‐(BTFPsulfonyl)acetamide ( 5 ) have successfully been employed in the Julia–Kocienski olefination of aldehydes with K 2 CO 3 as the base at 120 °C in DMF under solid/liquid phase‐transfer catalysis conditions to afford α,β‐unsaturated esters and Weinreb amides, respectively. The corresponding products were obtained in good yields and with high E stereoselectivities ( E / Z up to >99:1), especially in the case of the amides. A detailed computational study of the Julia–Kocienski olefination with BTFP sulfone 4 was carried out and confirmed the existence of an equilibrium in the initial addition of the sulfone enolate to the aldehyde and, in contrast to other proposed mechanisms, a non‐concerted final elimination of SO 2 and 3,5‐bis(trifluoromethyl)phenoxide. A plausible explanation for the high E diastereoselectivity observed in the reaction has been suggested based on kinetic considerations at spirocyclic TS2 and thermodynamic factors during the elimination after TS2 . ESI‐MS studies carried out during the olefination reaction of benzaldehyde with BTFP sulfone 4 were used to characterize the sulfone enolate and the intermediate assumed for the reaction mechanism. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)