A stereoselective synthesis of trisubstituted alkenes. Part 1. Nickel-catalysed coupling of Grignard reagents with 5-alkyl-2,3-dihydrofurans

Abstract

5-Alkyl-2,3-dihydrofurans 3a–j prepared by the alkylation of 5-lithio-2,3-dihydrofuran 2 with primary alkyl bromides and iodides, undergo Ni⁰-catalysed coupling with Grignard reagents to give homoallylic alcohols. The yield and stereoselectivity depend on the structure of the Grignard reagent with the best results being obtained with long chain primary Grignard reagents and Grignard reagents lacking β-hydrogens (Me, Ph, Me₃SiCH₂). 5-(1-Hydroxyalkyl)-2,3-dihydrofurans 20 and 21 are poor substrates for the coupling reaction. Mechanisms are proposed for the coupling as well as competing reduction and isomerisation reactions.