Allylation of (R)-2,3-O-Cyclohexylideneglyceraldehyde with Methyl 3-(Bromomethyl)but-3-enoate. Methyl 3-{(2S)-2-[(2R)-1,4-Dioxaspiro[4.5]dec-2-yl]-2-hydroxyethyl}but-3-enoate as a Convenient Universal Building Block for the Synthesis of Key Fragments of Bioactive Compounds

Abstract

(R)-2,3-O-Cyclohexylideneglyceraldehyde was involved in the Barbier allylation reaction with such 2-substituted functionalized allyl bromide as methyl 3-(bromomethyl)but-3-enoate under the action of various metals or metal salts. The best diastereoselectivity was observed with Zn and DMF or THF plus saturated aqueous ammonium chloride as solvents. The feasibility of the resulting homoallyl alcohol, specifically methyl 3-{(2S)-2-[(2R)-1,4-dioxaspiro[4.5]dec-2-yl]-2-hydroxyethyl}but-3-enoate, as a building block for the macrocyclic anticancer agents, such as laulimalides and their synthetic analogs.