Conjugate Addition and Subsequent Enolate Trapping with Electrophiles

Abstract

Significance: Asymmetric conjugate addition is one of the most powerful methods for C-C bond formation at the b-carbon. The potential exists for further elaboration at the a-carbon by in situ trapping of the metal enolate with electrophiles. The authors describe trapping of poorly reactive zinc enolates with activated electrophiles giving good to high yields and trans/cis products with excellent enantioselectivity.Comment: Copper-catalyzed conjugate addition has been extensively studied with various nucleophiles and subsequent trapping of the generated metal enolate provides highly functionalized compounds. Due to the mild reactivity of zinc enolates relative to other metal enolates, the second alkylation of the a-carbon is typically problematic. Previous reports stated the inability to directly accomplish zinc enolate trapping by electrophiles directly without additional reagents or transformations (A. Alexakis, O. Knopff Org. Lett. 2002, 4, 3835-3837). The paper solves this issue by using a reactive electrophile so that the zinc enolate can be directly alkylated without additional reagents. O R 2 Zn (1.2 equiv) Ligand (2 mol%) CuTc (1 mol%) Et 2 O, -30 °C O ZnEt O EWG LG (1.2 or 2.4 equiv) EWG EWG = NO 2 EWG = CO 2 Et EWG = SO 2 p-Tol EWG = P(O)(OEt) 2 LG = OPiv LG = Br 60-80% yield up to >98% trans/cis 91-99.1% ee Ligand = n n = 1 n = 2 O O P N Ph Ph SYNFACTS Contributors: