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

Abstract

Although phenylmethylene-protected vinyl sulfone-modified carbohydrate 2alpha reacts with both primary and secondary amines in Michael fashion to afford aminated products, only primary amines react with the dibenzyl-protected 3alpha, 6-O-trityl-protected 4alpha, and unprotected 5alpha, 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 2alpha and 5alpha 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.

1,1-Dioxothiomorpholines with asymmetric environments: protecting group directed diastereoselectivity of glyco divinyl sulfone cyclization

“…These carbohydrate derived DVSs react efficiently with primary amines to generate a new class of biologically relevant 1,1-dioxothiomorpholine derivatives. Our current study supports our earlier observations 17 that in addition to the anomeric congurations protecting groups also contribute signicantly to the addition patterns of intramolecular nucleophiles to DVS-modied carbohydrates.…”

“…16 However, the direct inuence of protecting groups on the reactivity of the non-anomeric carbons of sugar residue is scarcely reported. 17 Effect of protecting group on the intramolecular cyclization was evident in case of 4a. 8b Moreover, we recently reported the remarkable inuence of protecting groups on the reaction patterns of MVS-modied carbohydrates.…”

“…8b Moreover, we recently reported the remarkable inuence of protecting groups on the reaction patterns of MVS-modied carbohydrates. 17 It emerged from the earlier study 17 that the protecting groups present at C-6 and C-4 of MVS-modied hex-2-enopyranosides, namely benzyl-, dibenzyl-and 6-O-trityl-played an important role in determining the rate and the selectivity of addition of amines at C-2. 8b, 17 Thus, to identify whether the partially rigid bicyclic structure of 9a (and 10) resisted intramolecular cyclization, we replaced the cyclic protecting groups of 9 by acyclic ether linkages.…”

“…17 It emerged from the earlier study 17 that the protecting groups present at C-6 and C-4 of MVS-modied hex-2-enopyranosides, namely benzyl-, dibenzyl-and 6-O-trityl-played an important role in determining the rate and the selectivity of addition of amines at C-2. 8b, 17 Thus, to identify whether the partially rigid bicyclic structure of 9a (and 10) resisted intramolecular cyclization, we replaced the cyclic protecting groups of 9 by acyclic ether linkages. For the synthesis of the appropriate DVS-modied pyranosides, the 4,6-dibenzyl-protected a-anomeric epoxide 15a 18 was reacted with mercaptoethanol in the presence of TMG to generate 16a, which was oxidized to sulfone 17a using MMPP.…”

A Survey of Recent Synthetic Applications of 2,3-Dideoxy-Hex-2-enopyranosides

“…Michael additions, followed by desulfonylation with Na-Hg (6 mol-%) of the resulting adducts [62], allowed the regio- and stereo-selective introduction of nucleophiles in 2,3-eno-pyranosides. They found a remarkable influence of the protecting groups of the hydroxyl moieties on the reaction patterns [63]. For example, although phenylmethylene-protected vinyl sulfone 55 reacts with both primary and secondary amines in a Michael-fashion, only primary amines react with the dibenzyl-protected, O -trityl protected or unprotected derivatives 56 , 57 and 58 respectively (Figure 1).…”