Palladium-Catalyzed Suzuki-Miyaura, Heck and Hydroarylation Reactions on (-)-Levoglucosenone and Application to the Synthesis of Chiral y-Butyrolactones

Abstract

The chiral pool material (-)-levoglucosenone (6,8-dioxabicyclo[3.2.1]oct-2-en-4-one, LGO) has been substituted by using a series of Pd-mediated cross-coupling reactions. Iodination of LGO followed by Suzuki-Miyaura cross-coupling reaction with boronic acids by employing the Buchwald ligand SPhos with Pd(OAc)₂ afforded 3-aryl derivatives in excellent yields. Selective Heck arylation reaction at the 2-position was achieved with aryl iodides with K₃PO₄ as base and SPhos ligand with Pd(OAc)₂ (1-5 mol-%). A selective hydroarylation reaction (formal conjugate addition) was developed by using the same aryl iodides, benzyldiethylamine, Pd-(OAc)₂, and P(o-tol)₃. The products were converted, either directly or after alkene reduction, through a Baeyer-Villiger oxidation into chiral 3- and 4-substituted 5-(hydroxymethyl)-dihydrofuran-2(3H)-ones.