Experimental and theoretical study of the O3/O4 regioselectivity of glycosylation reactions of glucopyranosyl acceptors

d-Allose, a rare sugar. Synthesis of d-allopyranosyl acceptors from glucose, and their regioselectivity in glycosidation reactions

“…44 Nevertheless, acceptors 1 and 2 were more reactive at axial OH-3 with respect to equatorial OH-4 (Table 1 and Scheme 4). In line with our previous results, 15,16 lower regioselectivities were obtained when using the more reactive furanosic donor 5 (entries 3 and 4 vs. 2 and 3). When comparing the behavior of the acceptors with donor 5 , an increase in the relative reactivity of OH-4 was observed when passing from the benzylated to benzoylated acceptor (entries 3 and 4), thus diminishing the regioselectivity.…”

“…In our laboratory we have investigated the relative reactivity of OH-3 and OH-4 of 2,6-di- O -protected galacto- and glucopyranosyl derivatives in glycosidation reactions with different galactosyl donors. 15,16 In the case of d -Gal p acceptors, the formation of 1 → 3 disaccharides was favored, as expected, given the equatorial orientation of the OH-3 group vs. the axial one of the OH-4 group. However, the regioselectivities observed were different depending on the 2,6-substituents, the anomeric configuration of the acceptors, and the reactivities of the donors.…”

“…The structures were unequivocally assigned on the basis of NMR spectra. The position of the interglycosidic linkages was verified from the deshielding of the 13 C NMR signals involved in such linkages, 16 by the information provided by COSY and HMBC experiments (exemplified for compound 27 , ESI†), and by the free OH signal and the corresponding 3 J H,OH coupling constant observed in the 1 H NMR spectrum. The stereochemistries of the newly formed glycosidic linkages were established from the 3 J 1′,2′ coupling constants, which were around 8 Hz for disaccharides obtained from pyranosic donor 4 and 1–2 Hz for those obtained from furanosic donor 5 , 43 confirming in most cases the β-configuration, achieved as a result of the anchimeric assistance in benzoylated donors.…”

“…The same trend was observed for d -Glc p derivatives. 16 For donor 4 , a mixture of α- (42%) and β-(1 → 3) (53%) disaccharides was afforded when reacting with benzoylated acceptor 2 , and none of the 1 → 4 product was observed (entry 2). A 3 J 1′,2′ value of 3.6 Hz, characteristic of an α-galactopyranoside, was observed for disaccharide 19 .…”

“…15 For d -Glc p acceptors, with both OH-3 and OH-4 equatorially oriented, the prediction is not trivial and, in line with this, the experimental behavior showed larger variations and less accurate agreement with the theoretical results. 16…”