A 3,4‐trans‐Fused Cyclic Protecting Group Facilitates α‐Selective Catalytic Synthesis of 2‐Deoxyglycosides

Abstract

A practical approach has been developed to convert glucals and rhamnals into disaccharides or glycoconjugates with high a-selectivity and yields (77-97 %) using a trans-fused cyclic 3,4-O-disiloxane protecting group and TsOH·H 2 O (1 mol %) as a catalyst. Control of the anomeric selectivity arises from conformational locking of the intermediate oxacarbenium cation. Glucals outperform rhamnals because the C6 side-chain conformation augments the selectivity.

Silyl-protective groups influencing the reactivity and selectivity in glycosylations

“…Cyclic silyl protective groups were also recently found to have a beneficial influence on the α-selectivity obtained in glycosylations using glucals [ 65 ]. The reaction of 3,4- O -TIPDS-protected glucal 72 with acceptor alcohols such as 73 , catalyzed by p -TsOH, gave exclusively α-glucoside 74 ( Scheme 15 ).…”

“…Surprisingly the 6-deoxy version of 72 gave a lower α-selectivity. The observations were explained with the assistance of DFT calculations as being due to the TS structure (formed from 72 ) being in an α-selective 4 H 3 conformation with the 6-TIPS group in an electronically favored gauche–gauche conformation [ 66 ], that causes additional shielding from the β-face [ 65 ].…”

C–H···Anion Interactions Assisted Addition of Water to Glycals by Sterically Hindered 2,4,6-Tri-tert-butylpyridinium Hydrochloride

“…Silyl protecting groups occupy a significant position in synthetic organic chemistry and more so in carbohydrate chemistry. , It is well established that the silyl protecting groups that, in general, demand a huge steric space, and hence impose conformational restriction, offer better anomeric selectivities in glycosylation reactions. , However, the influence of silyl protecting groups in the chemistry of 2-deoxysugars, versatile intermediates in carbohydrate chemistry, has been under-explored because of the difficulty in synthesizing the 2-deoxy-hemiacetal precursors. The current methods for the synthesis of sugar lactols from glycals involve the use of highly acidic conditions like 4–8 M HCl or triphenylphosphine/HBr, under which some of the silyl protecting groups are usually unstable and lead to reduced yields or the decomposition of starting materials (Scheme a).…”

“…Silyl protecting groups occupy a significant position in synthetic organic chemistry 18 and more so in carbohydrate chemistry. 19,20 It is well established that the silyl protecting groups that, in general, demand a huge steric space, and hence impose conformational restriction, offer better anomeric selectivities in glycosylation reactions. 10,19 However, the influence of silyl protecting groups in the chemistry of 2deoxysugars, versatile intermediates in carbohydrate chemistry, has been under-explored because of the difficulty in synthesizing the 2-deoxy-hemiacetal precursors.…”

Deoxy sugars. General methods for carbohydrate deoxygenation and glycosidation

“…For example, by using triphenylphosphine with catalytic amounts of HBr, the Ferrier product is not formed and the product with α-stereoselectivity as a result of a syn addition from the α-phase is formed (Scheme 11B). Many successful strategies have already been developed to give access to 2-deoxyglycosides by addition of nucleophiles to glycals using different catalysis types, including acid catalysis, 51 metal-catalyzed glycosylation, 52–55 organo-catalyzed glycosylation, 51,56–61 photo-catalyzed glycosylation, 62,63 and even by electro-catalysis. 64…”