Mechanistic Study of Silyl-Assist Effect on 1,2-cis-α-Glucosylation

The stereoselectivity of the 1,2-cis-alpha-glucosylation reaction has been reported to be enhanced by introducing a tert-butyldimethylsilyl (TBS) protecting group into the glucosyl donor. Herein, the origin of this silyl-assist effect was identified using chemical experiments and density functional theory (DFT) calculations. Glucosylation reactions using various glucosyl donors with different TBS group positions showed that alpha-selectivity decreased when the TBS group position was further from the anomeric position. These systematic experiments showed that the silyl-assist effect was mainly due to electronic factors. Comparing DFT calculations of oxocarbenium intermediates derived from typical glucosyl donors showed that the introduced TBS group contributed to enhanced electron density at the anomeric position. Chemical experiments and DFT calculations showed that introducing a TBS group near the anomeric position stabilized the cationic intermediate and promoted alpha-selectivity.

Automated summary

The stereoselectivity of the 1,2-cis-alpha-glucosylation reaction can be enhanced by introducing a tert-butyldimethylsilyl (TBS) protecting group into the glucosyl donor. The silyl-assist effect was mainly due to electronic factors, as shown by chemical experiments and density functional theory (DFT) calculations.