W. George Overend

Titanium-mediated methylene transfer reactions on sugar esters, lactones, and uloses

The titanium alkylidene 1, a versatile methylenating agent readily derived’ from the rather costly Tebbe compound 2, has been used in Wittig-type reactions to convert ketones into olefins and esters into vinyl ethers’. We now reportt its application to a variety of sugar derivatives that contain carbonyl and/or ester functions, with the aim of delineating the scope of the reaction with respect to blocking groups and the structure of the ketone, ester, or lactone. In order to simplify the procedure and increase the value of the method, the unpurified form of 2 was used (see Experimental). Pure, crystalline Tebbe reagent has been used by others3t4 on some aldonolactones and, where comparisons can be made, both similarities and differences were found. Reaction of the ulose 3 (X = 0) and the aldehyde 5 (R = H) with 2 gave, after chromatography, 70% and 35%, respectively, of the olefins 4’*(’ and 6 (R = H)7 in experiments that were easier to execute than the customary Wittig procedure5. Mono-esters of sugars were converted smoothly into vinyl ethers. Thus, 1,2:5,6di-0-isopropylidene-u-D-glucofuranose 3-acetate, 3-benzoate, and 3-p-chlorobenzoate gave, in good yields, the respective substituted vinyl ethers 7 (R = Me, or Ph, or ClC6H4). Each of the vinyl ethers 7 was susceptible to hydrolysis and gave methyl ketones uiu hemiacetals. The stability of these compounds towards hydrolysis increased in the order cited. Esters of glycuronic acids reacted readily with the crude 2, thereby affording a route to chain-extended sugars. The methyl glucoronate derivative 8 gave the methylene compound 9, and the methyl galacturonate derivative 5 (R = OMe) gave compound 6 (R = OMe), which needed more careful handling than 9 because it was rapidly hydrolysed on silica gel with neutral eluants to give the useful ketone 5 (R = Me). The &lactones 2,3,4,6-tetra-O-methyl-p-glucono-1,5-lactone (10, R = Me) and

A comparison of the Wittig and Knoevenagel-Doebner reactions for the chain extension of aldoses

Reaction conditions are described for the chain extension of 2,3 : 5,6-di-O-isopropylidence-D-mannose (1) with a Wittig ylide (2) to give the acyclic manno-octenoate (3) or the C-glycofuranosides (4 and 5) and with the Knoevenagel–Doebner reaction to afford the isomeric gluco-octenoate (6); the isomerisation proved to occur in the latter reaction provides an explanation for an anomaly in the literature and indicates that the C-glycosides (4 and 5) are formed by a Michael-type ring closure rather than via a betaine intermediate.

Synthesis and some reactions of methyl 4,6-O-benzylidene-2,3-dideoxy-2-phenylazo-β-d-erythro-hex-2-enopyranoside

Abstract Methyl 4,6- O -benzylidene-2,3-dideoxy-2-phenylazo-β- d - erythro -hex-2-enopyranoside has been synthesised, and its addition reactions with methoxide, azide, hydride, and deuteride ions have been studied. Comment is made on the stereochemistry of addition reactions of 2- and 3-phenylazo derivatives of methyl 4,6- O -benzylidene-2,3-dideoxy- d -hex-2-enopyranosides.

The chemistry of some methyl anhydroglycosiduloses

Abstract Methyl anhydroglycosiduloses containing an αβ-epoxy carbonyl unit have been readily prepared by the oxidation of methyl 2,3-anhydro-β- L -ribopyranoside and methyl 3,4-anhydro-6-deoxy-α- L -mannopyranoside with ruthenium tetraoxide. The reactions of these epoxyketones at either the oxirane or carbonyl function with hydrogen-over-palladium, hydrochloric acid, hydrobromic acid, nitromethane, or diazomethane illustrate their versatility, and their application to the synthesis of amino and deoxy sugars is described, including a derivative of colitose.

The synthesis of some methy 4,6-O-Benzylidene-α-D-erythro-Hexopyranosid-2,3-Diulose derivatives

Abstract Methyl 4,6- O -benzylidene-3-deoxy-3-phenylazo-α- D -glucopyranoside ( 1 ) has been oxidised with the Pfitzner—Moffat reagent to the 2,3-diulose 3-phenylhydrazone derivative ( 2 ) which has been characterised as the phenylosazone ( 3 ) and oxime ( 4 ). An unstable 2-imino derivative ( 10 ) of the same diulose has been produced by base-catalysed elimination of nitrogen from methyl 2-azido-4,6- O -benzylidene-2-deoxy-α- D - ribo -hexopyranosid-3-ulose ( 8 ). The imino intermediate was trapped as a quinoxaline derivative ( 9 ). The base-catalysed reactions of certain other hydrazone derivatives of methyl hexosiduloses have also been examined.

Synthesis of 3-deoxy-D-manno-octulosonic acid (KDO)

2,3 : 5,6-Di-O-isopropylidene-D-mannose has been converted by five sequential reaction (Witting reaction, deacetonation, hydrogenation, lactonisation, and isopropylidenation) into 2, 3-dideoxy-5, 6: 7, 8-di-O-isopropylidene-D-octonolactone from which KDO could readily be obtained by hydrolysis.

Arylazo-glycenosides. Part V. Cycloadditions with methyl 5-O-benzoyl-2,3-dideoxy-3-phenylazo-α- and -β-D-glycero-pent-2-enofuranoside

Methods for the formation of fused bicyclic systems in which one of the rings is furanoid have been examined by studying the addition of acrylonitrile to methyl 5-O-benzoyl-2,3-dideoxy-3-phenylazo-α-or -β-D-glycero-pent-2-enofuranoside. 1,4-Cycloaddition occurs across these azoalkenes. Diazomethane and dimethyloxosulphonium methylide undergo 1,2-cis-addition across the carbon–carbon double bond of the α-D-azoalkene. The stereochemistry of the products has been studied by n.m.r. spectral methods. The adduct from the diazomethane reaction extrudes nitrogen when heated, and the product undergoes cyclisation to give a 4′,5′-dihydro-1′-phenyl-(methyl 5-O-benzoyl-2,3-dideoxy-α-D-pentofuranosido)[3,2-c]-Δ2′-pyrazole and methyl 5-O-benzoyl-2,3-dideoxy-2,3-C-methylene-3-phenylazo-α-D-lyxofuranoside. Comment is made on the mechanisms of some of the reactions studied.

Arylazo-glycenosides. Part 7. Syntheses of amino-sugars from methyl arylazo-hexenopyranosides

Reaction of the anhydro-glycopyranosiduloses (1) and (2) with o-nitro- and o,p-dinitro-phenylhydrazine yielded the hydrazones (3)–(6), whereas phenyl- or p-nitrophenyl-hydrazine yielded the phenylazoalkenes (7)–(10), formed by rearrangement of intermediate hydrazones. Reaction of the azoalkanes (8) and (9) with a range of nuceophiles yielded the α-substituted phenylhydrazones (11)–(19) and (24)–(28), respectively, by 1,4-addition. It has been shown that the α-amino-hydrazones (20), (25), and (28) can be reduced to vicinal diaminosugars, thereby providing a new route to these compounds. Reduction of the azoalkene (9) yielded the 2-amino-2,3,6-trideoxy-hexopyranoside, isolated as the ON-diacetyl derivative (31).

Synthesis of 3-amino-3,4-dideoxysugars

Sequential treatment of methyl 3,4-O-isopropylidene-β-L-erytho-pentopyranosidulose (1) with aqueous sodium hydroxide and phenylhydrazine results in elimination of acetone and formation of 2S-methoxy-tetrahydropyran-3,4-dione 4-phenylhydrazone (7) as the main product. Similarly, methyl 6S-deoxy-3,4-O-isopropylidene-α-L-lyxo-hexopyranosid-2-ulose (2) was converted into 2R-methoxy-6S-methyltetrahydropyran-3,4-dione 4-phenylhydrazone (8). The effect of base on the related uloside, methyl 6-deoxy-2,3-O-isopropylidene-α-L-lyxo-hexopyranosid-4-ulose (16), resulted in the formation of 3-hydroxy-2-methyl-4H-pyran-4-one (maltol)(17). Compounds (7) and (8) have been converted into, respectively, 3-amino-3,4-dideoxy-D-erythro-pentopyranose (22) and 3-amino-3,4,6-trideoxy-L-ribo-hexopyranose (25).

Arylazo-glycenosides. Part IV. Synthesis and reactions of some 2- and 3-arylazo-derivatives of methyl 2,3-dideoxy-D-pent-2-enofuranoside

A method for the modification of some methyl D-pentofuranosidulose derivatives at the position α to the carbonyl group has been studied. Preparations are described of some new 2- and 3-phenylazo- and p-nitrophenylazoderivatives of methyl 2,3-dideoxy-D-pent 2-enofuranoside using D-xylose as the initial material. The procedures adopted for the syntheses are essentially those developed in our laboratories for the preparation of phenylazoderivatives of sugars and described in Part I.The new arylazo-derivatives have been shown to be useful synthetic intermediates: they undergo 1,4-addition reactions in a highly stereoselective way with a wide range of nucleophiles. For example, the following have been used in addition reactions, ammonia and dimethylamine, water, acetic acid, methoxide and azide ions, hydride and deuteride ions, and a range of sulphur nucleophiles. Structures of the products have been established by analysis of their n.m.r. spectra.A brief examination is reported of the formation of methyl D-pentofuranosiduloses carrying a substituent at position α to the carbonyl group from their arylhydrazones, which are the initial products of the addition reactions.