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

Abstract

AbstractThe 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 K2CO3 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 SO2 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)