Deoxygenative Divergent Synthesis: En Route to Quinic Acid Chirons

Abstract

The installation of vicinal mesylate and silyl ether groups in a quinic acid derivative generates a system prone for stereoselective borane-catalyzed hydrosilylation through a siloxonium intermediate. The diversification of the reaction conditions allowed the construction of different defunctionalized fragments foreseen as useful synthetic fragments. The selectivity of the hydrosilylation was rationalized on the basis of deuteration experiments and computational studies.

O,O-Silyl Group Migrations in Quinic Acid Derivatives: An Opportunity for Divergent Synthesis

“…During our previous studies of the modification of quinic acid, 17 when attempting to convert a primary hydroxyl function of trisilylated quinic alcohol 1 into a sulfonate moiety, we observed multiple silyl migrations as an untraceable mixture of products. Considering that the diversification of a common precursor into several synthetic intermediates is a powerful tool for synthesizing molecules otherwise difficult or impossible to reach, and the limited number of studies on the O-silyl migration in carbacyles, we set out to improve the selectivity of the migration process (Scheme 1d).…”

“…To avoid regio-and diastereoselective issues in the opening of a cyclic siloxonium ion, we decided to proceed with the Barton−McCombie deoxygenation of 3a instead of using the previously explored borane-catalyzed deoxygenation with hydrosilanes. 17 The introduction of the O-thiocarbonyl group proved to be challenging due to the required use of a base and subsequent O,O-silyl group migrations. After failed attempts in preparing the thiocarbonylimidazolide or methyl xanthate from 3a, phenyl thionocarbonate 8 could be prepared in 89% yield (Scheme 4b) due to the high electrophilicity of phenyl chlorothionocarbonate.…”

“…We envisioned that the syntheses of the family of natural products 6 could be easily achieved by selective epoxide opening of key intermediate 10 with an organometallic reagent derived from the corresponding fatty acid, after deoxygenation of 3a (Scheme a). To avoid regio- and diastereoselective issues in the opening of a cyclic siloxonium ion, we decided to proceed with the Barton–McCombie deoxygenation of 3a instead of using the previously explored borane-catalyzed deoxygenation with hydrosilanes …”