Torsional disarming

The influence of the 4,6-O-benzylidene acetal in p-mannosylations was believed to be due to its torsional disarming effect. In an earlier work, Bert Fraser-Reid and coworkers found that a 4,6-O-benzylidene acetal locks the pyranose ring in a stable chair conformation [41], Therefore, it disfavors the formation of an intermediate oxocarbenium ion, which requires rehybridization and flattening of the sugar ring, usually leading to ahalf-chair conformation. This torsional effect, combined with the strong endo-mom nc effect in mannose, favors the a-triflate intermediate. 

The results in Scheme 4 suggest the affirmative (11). Thus, the conformationally mobile donor 14 gave mainly p-product 15 in poor yield however, the torsionally disarmed counterpart 16 gave a two-fold higher yield of a-product 17(72). The slow rate of reaction attributable to the torsional strain suffered by 16, is consistent with the long- lived intermediate 9b in Crich s p-mannoside synthesis. 

The 3,4-cyclohexylidene diacetal, which was introduced for the selective protection of trans diequatorial vicinal diols [33], is resistant to the flattening of carbohydrate ring required for the generation of an oxocarbonium ion intermediate and thus a torsionally disarming protecting group [15]. Similarly, the dispiroketal [15, 34]... 

Thus, the greatest disarming effect was seen from the 2-benzoyl substituent in compound 37, followed by the 4-benzoyl and 3-benzoyl substituents (in compounds 34 and 35, respectively). In addition, cyclic ketal 36 was found closer in reactivity to the mono-benzoylated rather than the di-benzoylated series of compounds. Not surprisingly, reactivity levels recorded for the mono-benzoylated (34, 35, 37), di-benzoylated (38-40), and torsionally disarmed (36) glycosyl donors fell in between the traditional per-benzylated armed rhamnoside 25 and its disarmed per-benzoy-lated counterpart 41. 

SCHEME 5.18 Armed-disarmed glycosylation based on torsional effects. 

The ester/acetal groups are disarmed by different mechanisms while esters disarm electronically, benzylidene and isopropylidene acetals were considered to be disarmed by torsional strain. This deactivation was extensively studied by Bols,180 who used the... 

Jcmscm HH, Ntndstrpm LU, Bols M (2004) The disarming effect of the 4,6-acetal group on glycoside reactivity torsional or electronic J Am Chem Soc 126 9205-9213... 

It is known that 4,6-0-benzylidene protection group in a saccharide reduces its reactivity (i.e., it disarms it) in glycosylation reactions. Thus, a thiosaccharide glycosyl donor with 4,6-0-benzylidene group 77 is less reactive toward reaction with methanol than its fully benzylated analog 78 (Fig. 5.22) [17]. This phenomenon, which has been attributed to torsional effects or more specifically to the... 

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