Metal-Free Route to Carboxylated 1,4-Disubstituted 1,2,3-Triazoles from Methoxycarbonyl-Modified Vinyl Sulfone

Abstract

A metal-free alternative to the regioselective synthesis of carboxylated 1,4-disubstituted 1,2,3-triazoles (1,4-cDTs) has been accomplished. A methoxycarbonyl-substituted vinyl sulfone on reactions with organic azides resulted in the formation of 1,4-cDTs in an operationally simple route. The reaction, carried out with a variety of organic azides containing free alcohol, acid, Boc-protected amine, ester, protected sugars, long-chain alkanes, benzyl, 9-methylanthracenyl, and cholesteryl groups, was found to be general in nature, which afforded a plethora of new chemical entities; reactions of diazides generated mostly the desired and a few unexpected products. This article reports for the first time the targeted metal-free synthesis of any 1,4-disubstituted 1,2,3-triazole using the cycloaddition reactions of an appropriately functionalized vinyl sulfone.

Synthesis of 1,4‐Disubstituted 1,2,3‐Triazoles from Terminal Vinyl Sulfones in Ionic Liquid: A Metal‐Free Eliminative Azide‐Olefinic Cycloaddition Route to Triazolyl Carbohydrates and Triazole‐linked Bissaccharides

“…All 1,4-DTs showed large and positive Δ(δC 4 -δC 5 ) values as reported for this class of compounds in literature; it has been reported in the literature that a large and positive value would indicate the presence of 1,4-DTs. [14] The Δ(δC 4 -δC 5 ) value of (18-23) obtained from the 13 C NMR spectra of 19-23 therefore confirmed the formation of 1,4-DTs. Additionally, the X-ray diffraction studies of the single crystal of 25 (ORTEP diagram in Scheme 7) unambiguously confirmed the formation of 1,4-DTs.…”

“…The regioselectivity [15] of 1,4‐ or 1,5‐DT formation was achieved in the past by the selection of properly functionalized vinyl sulfones which altered the polarity of the double bond under metal free conditions. Theoretical calculations in combination with the experimental findings established that the regioselectivity of triazole formation was controlled by the substituents attached to the β‐position of the vinyl unit [14,15] . The reaction patterns of non‐carbohydrate internal vinyl sulfones are depicted in Scheme 1 (A and B), which suggests that comparatively electron‐neutral groups (e. g. aryl, alkyl) would provide 1,5‐DTs (Scheme 1A) [15] whereas, electron withdrawing groups (e. g. CO 2 Me) would mostly afford 1,4‐DTs (Scheme 1B) [14] .…”

“…Theoretical calculations in combination with the experimental findings established that the regioselectivity of triazole formation was controlled by the substituents attached to the β‐position of the vinyl unit [14,15] . The reaction patterns of non‐carbohydrate internal vinyl sulfones are depicted in Scheme 1 (A and B), which suggests that comparatively electron‐neutral groups (e. g. aryl, alkyl) would provide 1,5‐DTs (Scheme 1A) [15] whereas, electron withdrawing groups (e. g. CO 2 Me) would mostly afford 1,4‐DTs (Scheme 1B) [14] . These observations were equally applicable to carbohydrate derivatives and therefore vinyl sulfone‐modified carbohydrates, on one hand afforded a plethora of 1,5‐DTs, 1,5‐DT‐modified carbohydrates and several 1,5‐DT linked bissacharides under metal‐free conditions [13,16] …”

“…During the last decade, we have established that vinyl sulfones, one such electron deficient olefins are much more easily obtained from 1,2‐diols, 1,2‐dibromides, olefins, epoxides and aldehydes because C−S bond formation is easily achievable even in the case of polyfunctionalized molecules [12,13] . The properly designed vinyl sulfones derived from a wide range of molecules serve efficiently as a good 2π partner in EAOC reactions and couple with organic azides in [3+2] cycloaddition reactions to afford a wide variety of 1,5‐DTs [13] or 1,4‐DTs [14] …”

An Overview on the ChemicalN‐Functionalization of Sugars and Formation ofN‐Glycosides

“…The electron withdrawing substituents reverse the partial charge generated on vinyl sulfones 77 as compare to vinyl sulfones 72 arose with a different route in reaction profile pathway to generate 1,4‐cDTs. Taking this ideology that vinyl sulfoxides as acetylene equivalents, the coupling of a methoxycarbonyl‐substituted vinyl sulfone 77 with glycosyl azides afforded 1,4‐disubstituted (1,4‐cDT)1,2,3‐triazole 78 via [3+2] cycloaddition (Scheme ) . The reaction proceed through intermediate A , followed by the elimination of p TolSO 2 H. Thus to conclude that, in case of simple vinyl sulfones elimination step resulted the usual formation of 1,5‐DTs while with carboxylated vinyl sulfone generated a series of 1,4‐cDTs.…”