Influence of the 4,6-O-Benzylidene, 4,6-O-Phenylboronate, and 4,6-O-Polystyrylboronate Protecting Groups on the Stereochemical Outcome of Thioglycoside-Based Glycosylations Mediated by 1-Benzenesulfinyl Piperidine/Triflic Anhydride and N-Iodosuccinimide/Trimethylsilyl Triflate

Abstract

The effect of 4,6-O-benzylidene acetals, 4,6-O-phenylboronate esters, and 4,6-O-polystyrylboronate esters on the stereoselectivity of couplings to galacto-, gluco-, and mannopyranosyl thioglycosides, otherwise protected with benzyl ethers, has been investigated by the benzenesulfinyl piperidine/trifluoromethanesulfonic anhydride (BSP), diphenyl sulfoxide/trifluoromethanesulfonic anhydride (Ph(2)SO), and N-iodosuccinimide/trimethylsilyl trifluoromethanesulfonate (NIS/TMSOTf) methods. The BSP and Ph(2)SO methods give comparable results in all three systems whereas the NIS method affords significantly different stereoselectivities in both the gluco and manno, but not the galacto series. The benzylidene acetal and boronate esters influence the stereochemistry in a similar manner in the beta-selective manno series and the alpha-selective galacto series but show significant differences with the glucose donors. The differences between the glucose, galactose, and mannose series reflect the established differences in reactivity and, especially for mannose, those in the anomeric effect and are best interpreted in terms of changes in the relative energetics between the alpha- and beta-covalent triflate intermediates and the various contact ion pairs with which they are necessarily in equilibrium.

The influence of acceptor nucleophilicity on the glycosylation reaction mechanism

“…21,22,29,40,43–47 It has been proposed that this selectivity originates from an in situ anomerization kinetic scheme, in which the initially formed α-triflate 5α anomerizes into its more reactive β-couterpart 5β . 21 Substitution of this species provides the α-glucosyl products.…”

Improved Synthesis of 1‐Benzenesulfinyl Piperidine and Analogs for the Activation of Thioglycosides in Conjunction with Trifluoromethanesulfonic Anhydride*

“…[2,10,22,23] While no actual comparisons between the BSP and Ph 2 SO methods of thioglycoside activation have been carried out in this study, other work from our laboratory leads us to agree with the conclusion of van Boom and co-workers. [24][25][26][27] We anticipate that between BSP, its analogs introduced here, the recent modification of Wong (23), [28] and diphenyl sulfoxide, a reagent will be found to activate almost all classes of thioglycoside, in conjunction with trifluoromethanesulfonic anhydride, under milder conditions than have hitherto been possible. [29][30][31] 2.…”

Stereoselective Synthesis of L‐Guluronic Acid Alginates

“…The conformationally constrained 4,6-O-benzylidene gulose 19 and 4,6-Odi-tert-butylsilylidene (DTBS) gulose 25 were selected on the basis of their reputation to influence the stereochemical outcome of glycosylations. [11,12] Gulose donor 24 and guluronate ester donor 22, with a selectively removable levulinoyl (Lev) group at the C-4 position, allow elongation to alginate oligomers with minimal protective-group manipulation. All four donor building blocks were assembled from phenyl-1-thio-b-l-gulopyranoside (6; Scheme 3).…”