Sequential Functionalizations of Carbohydrates Enabled by Boronic Esters as Switchable Protective/Activating Groups

Abstract

Processes for site-selective, sequential functionalizations of carbohydrate derivatives are described. In these processes, a tricoordinate boronic ester initially serves as a protective group for a sugar-derived 1,2- or 1,3-diol motif, permitting functionalization of free OH groups. In a second step, addition of a Lewis base generates a tetracoordinate adduct, which serves as an activating group, enabling functionalization of one of the boron-bound oxygen atoms by a second electrophile. By combining an initial acylation, alkylation, or glycosylation step with an amine-mediated glycosylation of the boronic ester, a variety of selectively protected di- and trisaccharide derivatives can be accessed in an operationally simple fashion without purification of intermediates. This Lewis base-triggered switching of behavior from "latent" to "active" nucleophile is a unique feature of boronic esters relative to other protective groups for diol moieties in carbohydrate chemistry.

Boron Effect on Sugar‐Based Organogelators

“…[8a, 9] In regard to the specific case of glucoside derivatives,t he boronic acid promotes the esterification of the hydroxy functionsa vailableo nt he 4-and6 -positions of the glucoside. [10] Boronic esters have alreadyb een involvedi no rganogelator structures, [11] but only few examples have taken advantageo ft his function for the preparation of sugar-based organogelators. [12] One importanti llustration related to our research work was described by Shimizu et al [12b-d] who designed al uminescent organogelator based on ag lycolipid naphthylb oronic ester.W ed escribed herein as eries of alkylglucoside phenylboronic esters 1 (Figure 1) easily prepared in as ingle chemical step.…”

“…Several strategies have been developed for the detection of sugars or for the formation of molecular self‐assembly, thanks to this easy and efficient reaction [8a, 9] . In regard to the specific case of glucoside derivatives, the boronic acid promotes the esterification of the hydroxy functions available on the 4‐ and 6‐positions of the glucoside [10] . Boronic esters have already been involved in organogelator structures, [11] but only few examples have taken advantage of this function for the preparation of sugar‐based organogelators [12] .…”

Recent advances in site-selective functionalization of carbohydrates mediated by organocatalysts

“…Initially, the boronic ester is used as a tricoordinate protecting group to enable free hydroxyl group functionalization. What follows is the addition of a Lewis base leading to formation of a tetracoordinate organoboron complex, which functions as an activating group to allow for further derivatization of a boron-bound oxygen [30]. Upon obtaining tricoordinate complex 11.2 , the authors treated it with triethylamine and silver (I) oxide to form tetracoordinate activating complex 11.5 .…”

Regioselective Ring Opening of 1,3‐Dioxane‐Type Acetals in Carbohydrates

“…In carbohydrate chemistry, however, protecting groups play a more sophisticated and subtle role that is not limited to the protection of chemically vulnerable hydroxyl, amino and carbonyl moieties from non‐chemoselective transformations. A well‐considered choice of protecting groups can steer the stereoselectivity during glycosylations, allow for regioselective manipulations, control the stereochemistry during chiral derivatization reactions,, or facilitate purification and identification . Furthermore, some protecting groups may serve as visualization handles,, while the use of isotopically labelled protecting groups allows the monitoring of the progress of glycosylations on solid support .…”