An Experimental and Theoretical Study on the Remarkable Influence of Protecting Groups on the Selectivity of Addition of Amines to Vinyl Sulfone-Modified Hex-2-enopyranosides

Although phenylmethylene-protected vinyl sulfone-modified carbohydrate 2α reacts with both primary and secondary amines in Michael fashion to afford aminated products, only primary amines react with the dibenzyl-protected 3α, 6-O-trityl-protected 4α, and unprotected 5α, highlighting for the first time the remarkable influence of protecting groups on the reaction patterns of vinyl sulfone-modified carbohydrates. The quantum chemical calculations suggest that the Michael addition of amines and proton transfer to vinyl sulfone-modified carbohydrates 2α and 5α are possible via relay process in a concerted mechanism. These calculations reveal that the addition of primary amines to vinyl sulfone-modified carbohydrate is preferential due to the low activation energy barriers, whereas the addition of secondary amines has relatively higher activation energy barriers. The theoretical conclusions are in line with the experimental observations.