Highly Selective Primary Alkoxycarboxylation and Esterification of Unprotected Pyranose Derivatives Mediated by Scandium(III) Triflate Catalysis

Abstract

A highly selective method for the alkoxycarboxylation and acylation of primary alcohols of pyranose derivatives is described. The reaction is high yielding and proceeds under mild conditions with 0.15–1 mol‐% Sc(OTf)3 used in combination with anhydrides or pyrocarbonates at 40–50 °C. Selectivities observed for alkoxycarboxylation of unprotected pyranose derivatives are > 95 %, and this constitutes a significant advantage over existing methods. Mechanistic implications, including the role of steric demand and metal–heteroatom coordination are also discussed.

A Rapid and Practical Catalytic Esterification for the Preparation of Caffeic Acid Esters

“…To our surprise, cinnamic acid afforded an almost quantitative yield of its phenethyl ester under 5 mol% ytterbium triflate (entry 25). Other substituted cinnamic acids also gave good yields (entries [26][27][28][29][30]. Despite a rather low reaction rate, these cinnamic acids produced less side products and gave better isolated yields than caffeic acid.…”

“…Lewis acid catalysts including metal triflates have been well documented for the esterification of carboxylic acids. [27][28][29] However, to the best of our knowledge the successful catalytic esterification of caffeic acid using only Lewis acids has not yet been reported. In 2013, Mamidi and Manna 30 reported a Zn(OTf) 2 -promoted esterification, in which an excess of Ph 3 P/ I 2 (2.0 equiv.)…”

Synthetic Approaches to the New Drugs Approved during 2019

“…This form was further crystallized from water and acetonitrile to provide remogliflozin etabonate hemihydrate in 62% yield. It should be noted that an alternate synthesis of remogliflozin etabonate hemihydrate from 207 in 92% yield using diethyl pyrocarbonate and catalytic scandium triflate has been reported . While this route is higher-yielding than the approach outlined in Scheme , use of the scandium triflate catalyst is unlikely to be economically viable on industrial scale.…”