Chemoselective glycosylations using sulfonium triflate activator systems

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.…”

“…[1] BSP met these criteria admirably and activates most thioglycosides for coupling in a matter of minutes at −60 °C as demonstrated in a series of subsequent synthetic endeavors from this [3][4][5][6][7] and other laboratories. [8][9][10][11][12][13] The highly crystalline nature of BSP, however, limits its solubility below −60 °C, which explains the choice of this temperature for coupling reactions as opposed to the more convenient −78 °C achieved with dry ice/acetone cooling baths. This minor inconvenience and, more importantly, the recognition that liquid analogs of BSP might ultimately prove preferable in automated oligosaccharide synthesis applications requiring robotic dispensation prompted the synthesis and evaluation of other sulfinamides as described here.…”

Methodology Development and Physical Organic Chemistry: A Powerful Combination for the Advancement of Glycochemistry

“…Building on earlier work by Gin and coworkers on the use of hemiacetals as glycosyl donors, 42 the van Boom group subsequently showed the combination of diphenyl sulfoxide and triflic anhydride to be an even more potent reagent for thioglycoside activation at low temperature. 43 Numerous related reagents have subsequently been developed by other groups. 44 In terms of practical improvements we also introduced TTBP as a less hygroscopic, more crystalline and less volatile alternative to the widely employed non-nucleophilic 2,6-di- tert -butylpyridine bases.…”

“…This latter process is such that neither sialyl sulfoxides nor sialyl trichloroacetimidates have been described in the literature; fortunately, in recent years the Yu group demonstrated that stable N -phenyl trifluoroacetimidates of sialic acid derivatives could be prepared and employed. 133 Adapting Gin’s dehydrative glycosylation method, 134 as generally developed for thioglycoside activation by the van Boom group, 43a we were able to activate sialyl thioglycosides in dichloromethane solution with combinations of diaryl sulfoxides and triflic anhydride. 135 Working with a single equivalent of sulfoxide and in the absence of an acceptor the 2,3-glycal 79 was the only observed product, pointing to the instability of any putative glycosyl triflate intermediates and of the oxocarbenium ion.…”

Influence of 4′-O-Glycoside Constitution and Configuration on Ribosomal Selectivity of Paromomycin

“…We show that the activity and especially the ribosomal selectivity of these paromomycin glycosides is configuration dependent and we construct a model and a rationale for their selectivity to guide future work on the synthesis of less toxic and more active AGAs. For the coupling reactions, the thioglycosides were activated with either diphenyl sulfoxide and trifluoromethanesulfonic anhydride 78 in the presence of tri-tert-butylpyrimidine, 79 or with the NIS/trifluoromethanesulfonic acid combination. 80,81 Trichloroacetimidates were activated with either boron trifluoride etherate or trifluoromethanesulfonic acid.…”