Silyl-protective groups influencing the reactivity and selectivity in glycosylations

Beilstein Journal of Organic Chemistry ◽

10.3762/bjoc.13.12 ◽

2017 ◽

Vol 13 ◽

pp. 93-105 ◽

Cited By ~ 29

Author(s):

Mikael Bols ◽

Christian Marcus Pedersen

Keyword(s):

Organic Chemistry ◽

Protective Group ◽

Carbohydrate Chemistry ◽

Protective Groups ◽

Silyl Groups ◽

High Stereoselectivity ◽

Glycosyl Donors

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.

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Silylated Sugars – Synthesis and Properties

Synlett ◽

10.1055/s-0040-1719854 ◽

2021 ◽

Author(s):

Mikael Bols ◽

Tobias Gylling Frihed ◽

Martin Jæger Pedersen ◽

Christian Marcus Pedersen

Keyword(s):

Protective Group ◽

Carbohydrate Chemistry ◽

Sugar Alcohols ◽

Protective Groups ◽

Silyl Groups ◽

Conformational Alteration ◽

Glycosyl Donors

AbstractSilicon has been used in carbohydrate chemistry for half a century, but mostly as a protective group for sugar alcohols. Recently, the use of silicon has expanded to functionalization via C–H activation, conformational arming of glycosyl donors, and conformational alteration of carbohydrates. Silicon has proven useful as more than a protective group and during the last one and a half decades we have demonstrated how it influences both the reactivity of glycosyl donors and stereochemical outcome of glycosylations. Silicon can also be attached directly to the sugar C-backbone, which has even more pronounced effects on the chemistry and properties of the molecules. In this Account, we will give a tour through our work involving silicon and carbohydrates.1 Introduction2 Conformational Arming of Glycosyl Donors with Silyl Groups3 Silyl Protective Groups for Tethering Glycosyl Donors4. Si–C Glycosides via C–H Activation4.1 C–H Activation and Oxidation of Methyl 6-Deoxy-l-glycosides4.2 Synthesis of All Eight 6-Deoxy-l-sugars4.3 Synthesis of All Eight l-Sugars by C–H Activation4.4 Modification of the Oxasilolane Ring5 C–Si in Glycosyl Donors – Activating or Not?6 Si–C-Substituted Pyranosides7 Perspective

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Azidation of Partially Protected Carbohydrate Derivatives: Efficient Suppression of Acyl Migration

Synlett ◽

10.1055/s-0040-1707137 ◽

2020 ◽

Vol 31 (15) ◽

pp. 1491-1496

Author(s):

Leonid O. Kononov ◽

Elena V. Stepanova ◽

Alexander I. Zinin ◽

Polina I. Abronina ◽

Alexander O. Chizhov

Keyword(s):

Organic Chemistry ◽

Phase Transfer ◽

Acyl Migration ◽

Hydroxyl Group ◽

Azido Group ◽

Protective Group ◽

Reaction Conditions ◽

Free Hydroxy Group ◽

Efficient Suppression ◽

Protective Groups

Although azidation by nucleophilic substitution is widely used in organic chemistry, it has a limitation for partially protected carbohydrate derivatives under typical reaction conditions used for azidation (heating with NaN3, phase-transfer catalyst (optional), DMF or DMSO) as it can cause substantial migration (70%) of O-acyl protective groups. Several approaches, including the use of a temporary protective group for the unprotected hydroxyl group, to avoid acyl migration have been compared. Addition of excess of ethyl trifluroacetate effectively suppressed benzoyl migration but inhibited substitution of the chlorine atom with the azido group. The most robust procedure involved addition of excess n-butyl formate to the reaction mixture. When this protocol was followed, migration of benzoyl groups in lactose derivatives with free hydroxy group at C-3′ or C-4′ was reduced to 4%, with the yield of the target, partially protected derivatives with an azido group in the aglycone approaching 92%.

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