Silyl-protective groups influencing the reactivity and selectivity in glycosylations

Abstract

Silyl groups such as TBDPS, TBDMS, TIPS or TMS are well-known and widely used alcohol protective groups in organic chemistry. Cyclic silylene protective groups are also becoming increasingly popular. In carbohydrate chemistry silyl protective groups have frequently been used primarily as an orthogonal protective group to the more commonly used acyl and benzyl protective groups. However, silyl protective groups have significantly different electronic and steric requirements than acyl and alkyl protective groups, which particularly becomes important when two or more neighboring alcohols are silyl protected. Within the last decade polysilylated glycosyl donors have been found to have unusual properties such as high (or low) reactivity or high stereoselectivity. This mini review will summarize these findings.

Automated Quantification of Hydroxyl Reactivities: Prediction of Glycosylation Reactions

“…However, not all of these trends can be explained by basic steric and electronic effects. Therefore, there must be other factors that influence the reactivity of alcohols in glycosylation reactions, such as intramolecular hydrogen bonding, [8b, 19] conformation [11c–g, 20] and bond rotation [7a, e, 21] . With the Aka index, we noticed α‐methyl glycoside usually gives higher nucleophilicity than β‐tolyl thioglycoside [for example, 6‐OH glucoside: 31 (7.16) vs. 32 (5.86); 4‐OH glucoside: 37 (3.51) vs. 38 (2.68); 2‐OH mannoside: 49 (4.77) vs. 51 (2.90)].…”

A Novel Glycosyl Donor with a Triisopropylsilyl Nonparticipating Group in Benzyl-Free Stereoselective 1,2-cis-Galactosylation

“…47 It is important to note that a larger number of bulky silyl (especially TIPS) groups in a glycosyl donor does not result in higher 1,2-cis stereoselectivity of glycosylation, 48 although it increases the reactivity of the glycosyl donor. 49 Scheme 6 Conformational changes in glycosyl cation induced by the bulky 2-O-TIPS group may favor syn attack of a nucleophile leading to 1,2-cis product…”

Conformational Lock of Glycosyl Donors Using Cyclic Carbamates

“…[ 18 ] Surprisingly tethering the 2,4 hydroxyl groups in a glucosyl donor did not result in the same dramatic reactivity boost. [ 19–21 ] Interestingly, Demchenko found that introducing a 2‐ O ‐benzoyl group in a perbenzylated glucosyl donor did increase the reactivity by anchimeric assistance. [ 22,23 ] This concept, also termed superarmed, [ 24 ] was later combined with the conformationally superarming, albeit resulting in slightly less reactive glycosyl donors.…”