All-E-Carotenoid Synthesis via Suzuki Coupling of α,ω-Dibromopentaene: HPLC Optimization of the Catalytic Reaction Conditions.

Abstract

C12 all-E-1,10-dibromo-3,8-dimethyldeca-1,3,5,7,9-pentaene (5) was prepared by double Ramirez dibromo-olefination of readily available C10 all-E-2,7-dimethylocta-2,4,6-trienedial (3) using CBr4 and PPh3, followed by the Hirao reduction of gem-dibromide using dimethyl phosphite and Et3N. The bidirectional double Suzuki coupling of 5 with C14 boronic acid pinacol esters (B-Pin) derived from various ionones or cinnamaldehyde produced all-E-β-carotene 1a, all-E-lycopene 1b, all-E-isozeaxanthin 1c, and all-E-phenyl-carotene 1d in high yields. The optimized catalytic reaction condition was determined by controlling the relative rate of each step in the cross-coupling mechanism by varying the base, solvents, and Pd catalyst, including the ligand. Information about the relative rate of each step was obtained from the reaction profiles generated from HPLC chromatograms over the reaction time. The double Suzuki coupling reaction is best suited for the synthesis of symmetrical all-E-carotenoids, whereas the Z-carotene prepared from the corresponding Z,Z-dibromopentaene 7 readily isomerizes to afford a mixture of stereoisomers. The generality of the Suzuki coupling reaction of dibromopentaene 5 was demonstrated by the concise and high-yield syntheses of short all-E-aryl-carotenoids 20-27 with various aryl boronic acids.