Double Diastereoselection, Regioselectivity, and the Importance of Donor-Acceptor Complementarity in the Stereoselectivity of Glycosylation Reactions

Abstract

Glycosylation is a process involving the union of two chiral partners, a donor and an acceptor, and is therefore formally subject to double diastereodifferentiation. In this review, we discuss, through the presentation of suitable examples, double diastereoselection in glycosylation reactions based on the "matched and mismatched concept". We also discuss the related but more widely appreciated concept of regioselective glycosylation of diols and illustrate through select examples how this may vary on the basis of donor and even promoter. Finally, we diverge from the usual course of representation of glycosylation stereoselectivity as a simple ratio, and also represent it in terms of diastereomeric excess to facilitate comparison with other branches of organic chemistry.

Neighboring‐Group Participation by C‐2 Ether Functions in Glycosylations Directed by Nitrile Solvents

“…Although the glycosylation of the secondary mannosyl acceptor 28 afforded only modest a-selectivity (Table 2, entry 11), [46] It may be attributable to a mismatching coupling between the glycosyl donor and acceptor. [47][48][49] After confirming the efficiency of the 1,2-trans-directing effect of the C-2 ether function, the synthesis of the target arabinans was carried out. For the purpose of comparison, both convergent and one-pot glycosylation strategies were examined.…”

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

“…Perhaps one of the more important issues that has come to light, and that one pertains to the much broader question of stereoselective glycosylation in general especially when conducted in an automated manner so as to provide large arrays for screening, is that of matched and mismatched donor acceptor pairs. A report of apparent matching in the synthesis of a mannan fragment has appeared in the literature, 71 but, as we have discussed elsewhere, 73 it is the growing number of examples of mismatching 74 that sound the warning bells.…”

“…63c,73 To this end we demonstrated early on that carbohydrate-based thiols are excellent acceptors in the 4,6- O -benzylidene directed β-mannosylation process. 117 Less predictably, as we have showed recently, simple carbon-based nucleophiles such as allyl silanes and stannanes and silyl enol ethers show the same selectivity patterns as alcohols in these glycosylation reactions.…”

Probing the Influence of a 4,6-O-Acetal on the Reactivity of Galactopyranosyl Donors: Verification of the Disarming Influence of thetrans–gaucheConformation of C5–C6 Bonds

“…48–50 With the related 4,6- O -di-( tert -butyl)silylene acetal protected galactopyranosyl donors α-selectivity is observed whether or not a participating group is present at C2. 51–55 This apparent ability of 4,6- O -benzylidene and 4,6- O -silylene acetals to direct galactopyranosylation toward selective formation of the α-anomer even in the presence of participating groups at the 2-position has been variously explained as arising from i) stabilization of a galactosyl oxocarbenium ion by O4 and O6 due to the conformation imposed by the presence of the benzylidene acetal, 46 ii) steric factors due to shielding of the β-face of the oxocarbenium ion by the acetal, 54 and iii) stereochemical mismatching 56–57 of donor/acceptor pairs, 48 It has also been noted in some cases that the selectivity is Lewis acid and condition dependent, with the softer BF 3 OEt 2 affording higher β-selectivities than the harder TMSOTf. 49 In an attempt to shed light on this issue, by adapting the method of Bols and coworkers, 29 we have studied and report here on the effect of a 4,6- O -alkylidene group and carba-analogs thereof on the hydrolysis of 2,4-dinitrophenyl galactopyranosides.…”