Vinyl Sulfone-modified Carbohydrates Research Articles

Vinyl sulfone-modified carbohydrates: Michael acceptors and 2π partners for the synthesis of functionalized sugars and enantiomerically pure carbocycles and heterocycles.

Increasing demands for molecules with skeletal complexity, including those of stereochemical diversity, require new synthetic strategies. Carbohydrates have been used extensively as chiral building blocks for the synthesis of various complex molecules. On the other hand, the vinyl sulfone group has been identified as a unique functional group, which acts either as a Michael acceptor or a 2π partner in cycloaddition reactions. A combination of the high reactivity of the vinyl sulfone group and the in-built chiralities of carbohydrates has the potential to function as a powerful tool to generate a wide variety of enantiomerically pure reactive intermediates. Since CS bond formation in carbohydrates is easily achieved with regioselectivity, further synthetic manipulations of these thiosugars has led to the generation of a wide range of vinyl sulfone-modified furanosyl, pyranosyl, acyclic, and bicyclic carbohydrates. Several approaches have been studied to standardize the preparative methods for accessing vinyl sulfone-modified carbohydrates at least on a gram scale. Reactions of these modified carbohydrates with appropriate reagents afford a large number of new chemical entities primarily via (i) Michael addition reactions, (ii) desulfostannylation, (iii) Michael-initiated ring-closure reactions, and (iv) cycloaddition reactions. A wide range of desulfonylating reagents in the context of sensitive molecules such as carbohydrates have also been extensively studied. Applications of these strategies have led to the synthesis of (a) amino sugars and branched-chain sugars, (b) C-glycosides, (c) enantiomerically pure cyclopropanes, five- and six-membered carbocycles, (d) saturated oxa-, aza-, and thio-monocyclic heterocycles, (e) bi-and tricyclic saturated oxa and aza heterocycles, (f) enantiomerically pure and trisubstituted pyrroles, (g) 1,5-disubstituted 1,2,3-triazolylated carbohydrates and the corresponding triazole-linked di- and trisaccharides, (h) divinyl sulfone-modified carbohydrates and densely functionalized S,S-dioxothiomorpholines, and (i) modified nucleosides. Details of reaction conditions were incorporated as much as possible and mechanistic discussions were included wherever necessary.

A metal free aqueous route to 1,5-disubstituted 1,2,3-triazolylated monofuranosides and difuranosides

Vinyl sulfones and vinyl sulfone-modified carbohydrates were subjected to 1,3-dipolar-cycloaddition reactions with four different azidofuranosides having azido groups at the C5 and C6-positions under refluxing conditions in aqueous media without any metal catalyst to afford the 1,5-disubstituted 1,2,3-triazolylated monofuranosides and difuranosides in high yields. These syntheses of 1,5-disubstituted triazolylated monosaccharides as well as 1,5-disubstituted 1,2,3-triazole linked disaccharides open up a new possibility of connecting furanosides with a stable-triazole backbone. [Display omitted]

Influence of steric bulk around the vinyl sulfone bond on the reaction patterns of vinyl sulfone-modified carbohydrates. An experimental and theoretical investigation

Influence of steric bulk around the vinyl sulfone bond on the reaction patterns of vinyl sulfone-modified carbohydrates. An experimental and theoretical investigation

An insight into our research on vinyl sulfone-modified pyranosides and furanosides

Abstract This review describes the research by the authors on the synthesis of vinyl sulfone-modified carbohydrates and the application of this new class of Michael acceptors in the generation of a wide range of aminosugars, branched-chain sugars, cyclopropanted carbohydrates, densely functionalized cyclopropanes, isonucleosides and pyrroles.

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 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.

A Diastereoselective Unique Route to Cyclopropanes Functionalized at All Three Ring Carbon Atoms from Acyclic Vinyl Sulfone-Modified Carbohydrates

In a departure from the current trend of using metal-catalyzed routes to cyclopropanation, pentosyl and hexosyl vinyl sulfone-modified carbohydrates having the terminal double bond and a suitably positioned leaving group are reacted in a stereoselective fashion with a series of nucleophiles to yield a myriad of cyclopropanes substituted at all three ring carbon atoms.

Densely Functionalized Chiral Pyrroles from Endocyclic, Exocyclic, and Acyclic Vinyl Sulfone-Modified Carbohydrates

A wide range of vinyl sulfone-modified carbohydrates have been prepared as starting materials for the synthesis of polysubstituted chiral pyrroles. All these vinyl sulfones reacted efficiently with ethylisocyanoacetate to generate a plethora of new pyrrole derivatives. Furanosyl rings opened up during pyrrole synthesis, and pyranosyl rings were opened up by reacting the pyrrole with POCl(3)/DMF. This paper also reports one of the most efficient and practical routes for the synthesis of beta-substituted pyrroles.

Diastereoselective addition of planar N-heterocycles to vinyl sulfone-modified carbohydrates: a new route to isonucleosides

Michael-type addition reactions of planar N-heterocycles at the C-2 positions of vinyl sulfone-modified carbohydrates provide an efficient and general route for the carbon– N-heterocycle bond formation. Therefore, the addition pattern of planar heterocycles, such as imidazole, triazole, thymine, and adenine to 3- C-phenylsulfonyl-hex-2-enopyranosides ( 1α/ 1β) and 3- C- p-toluenesulfonyl-pent-2-enofuranosides ( 2α/ 2β) was studied for developing a general methodology for the synthesis of new classes of isonucleosides possessing a carbon– N-heterocycle linkage at C-2 positions of furanosyl and pyranosyl sugars. To a great extent, the anomeric configurations of the starting vinyl sulfones play crucial roles in deciding the diastereoselectivity of addition of heterocycles. However, the trityl protected 3- C- p-toluenesulfonyl-hex-2-enopyranosides ( 33α/ 33β) were judged to be more practical starting materials for desulfonylation and deprotection for the synthesis of a new class of thymine and adenine deoxyisonucleosides.

Diastereoselective Michael Initiated Ring Closure on Vinyl Sulfone-Modified Carbohydrates: A Stereospecific and General Route to α-Substituted Cyclopropanes

Suitably designed vinyl sulfone-modified furanosides act as substrates for Michael initiated ring closure reactions yielding cyclopropanated carbohydrates. The strategy is general in nature and gives access to cyclopropanes with predefined chiralities on three consecutive carbons with varying substitutions at the alpha-position.

Diastereoselective C−C Bond Formation at C-5 of Vinyl Sulfone-Modified Hex-5-enofuranosyl Carbohydrates: Diversity-Oriented Synthesis of Branched-Chain Sugars and Beyond

This is the first report on the diastereoselective addition of carbon nucleophiles to vinyl sulfone-modified hex-5-enofuranosides. The stereoelectronic properties of the substituents at the C-3 position and their interactions with the incoming carbon nucleophiles control the diastereoselectivity of addition at the C-5 position, favoring the formation of l-ido derivatives as major products in most of the cases studied. This new concept of stereocontrolled carbon-carbon bond formation in vinyl sulfone-modified carbohydrates is general in nature. The novel chirons generated by this diversity-oriented synthetic method have been implemented in the preparation of a wide range of hexofuranosyl C-5 branched-chain sugars, bicyclic derivatives, chirally pure enals, and densely functionalized carbocycles.

Anomeric configuration-directed diastereoselective C-C bond formation in vinyl sulfone-modified carbohydrates: a general route to branched-chain sugars.

[structure: see text] This is the first report on the diastereoselective addition of carbon nucleophiles to vinyl sulfone-modified hex-2-enopyranosides and pent-2-enofuranosides. Nucleophiles add to the C-2 position from a direction opposite to that of the disposition of the anomeric methoxy group. This novel concept of anomeric configuration-directed stereocontrolled carbon-carbon bond formation in vinyl sulfone-modified carbohydrates is general in nature and has been implemented in the synthesis of new hexopyranosyl and pentofuranosyl branched-chain sugars and densely functionalized carbohydrates.

Vinylsulfone-modified carbohydrates: first general route to d-lividosamine (2-amino-2,3-dideoxy- d-glucose) and its new analogues

A general route to d-lividosamine and its new analogues has been devised for the first time. The essence of the present synthetic route lies in the diastereoselective introduction of N-monoalkylated and N-dialkylated amines to C-2 carbons of methyl 2,3-dideoxy-3-C-phenylsulfonyl- α- d-hex-2-enopyranoside and methyl 2,3-dideoxy-3-C-phenylsulfonyl- β- d-hex-2-enopyranoside in equatorial configurations. The 2-amino-2,3-dideoxysugrs thus generated, are desulfonated reductively at C-3 sites to produce a known intermediate for the synthesis of d-lividosamine and several new 2- N-alkylamino- and 2- N, N-dialkylamino-2,3-dideoxy analogues.