Stereoselective Double Alkylation of the Acetoacetate Ester α-Carbon on a d-Glucose-Derived Template: Application to the Synthesis of Enantiopure Cycloalkenones Bearing an Asymmetric Quaternary Carbon

Abstract

The previously developed D-glucose derivative, i.e., methyl 6-deoxy-2,3-di-O-(tert-butyldimethylsilyl)-a-D-glucopyranoside, served as a significant stereocontrolling element for the diastereoselective alkylation of the α-carbon in its acetoacetate at C-4 with two types of alkyl halides. The thus obtained doubly alkylated acetoacetate moiety bearing both methyl and allyl groups was efficiently converted into functionalized cycloalk-2-en-1-one derivatives by means of an intramolecular aldol strategy. Furthermore, the synthetic utility of the cycloalkenones was exemplified through the 1,4-addition to the thus obtained cyclopentenone derivative.