Using Unsaturated Carbohydrates

SCHEME 11.10 Reagents i MeLi, CuBr, Me2S ii (1) Ph3PCH2 and (2) Raney-Ni, EtOAc. 

As already mentioned, unsaturated sugars, particularly glycals, are readily available compounds. Perrier rearrangement of glycals in the presence of Lewis acids and alcohols easily takes place to provide 2,3-unsaturated carbohydrates. The allylic esters obtained this way can be engaged in different reactions with organometallic reagents. 

SCHEME 11.14 Reagents i MeCuCNLi ii RCuCNLi iii Wilkinson catalyst, H2. 

SCHEME 11.16 Reagents i EtjZn, CH2CI2, 96% ii (1) Hg(Cp3COO)2, THF, then NaCl and (2) BujSnH, 81% iii MS2O, EtjN, 84%. 

SCHEME 11.17 Reagents i (1) TESCl, imidazole, EtjN, CH2CI2 and (2) EtjZn, CH2I2, toluene ii (1) CSA, H2O THE, (2) NaH, PMBCl, DMF, (3) PyrHBrs, pyridine, H2O, THF and (4) BusSnH, AIBN, toluene. 

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In connection with our longstanding interest on the preparation of carbohydratelike molecules [13-16] as well as the applications of carbohydrates to the synthesis of natural [17,18] and unnatural products [19-21], we have had the opportunity to use unsaturated carbohydrates for the synthesis of peptide-carbohydrate hybrids [22-26], as well as functionalized heterocycles and alkaloids [27-29], and an outline of our recent results is reported herein. 

The term glycal is used to define sugar derivatives having a double bond between C-1 and C-2. Accordingly, C-1 glycals are A1,2 unsaturated carbohydrate derivatives with a carbon substituent at the anomeric position. These compounds are versatile synthetic intermediates, owing to the variety of transformations associated with their enol ether functionality, and have found ample use in the preparation of C-glycosyl compounds,1 carbohydrate mimics,2 and natural products.3... 

The increased availability of methods for the preparation of unsaturated sugars107 has stimulated interest in addition reactions of these compounds the use of unsaturated carbohydrate derivatives as precursors for specifically halogenated sugars has been widely exploited. 

A new method of stereoselective synthesis of thiodisaccharides by conjugate addition of l-thio-/J-D-glucose (8a) or 1-thio-a-L-fucose (30b) to an unsaturated carbohydrate molecule was also used for the preparation of D-glucopyrano-syl- and of L-fucopyranosyl-thiodisaccharides [56]. 

Compounds of this category are vinyl ethers having double bonds between C-l and C-2 of pyranoid or furanoid aldose derivatives. Analogues with exocyclic C-l-C-2 double bonds in cyclic 2-ketoses are sometimes referred to as evo-glycals and are covered briefly in Section IV.3 isomers with C-2-C-3 unsaturation in 2-ketoses can be considered as C-l-substituted glycals and are referred to in Section II.3.a. Together the glycals and their derivatives constitute the most useful set of unsaturated carbohydrate derivatives for application in synthesis. 

A combination of acetic acid and PDC has also been used to effect selective allylic oxidations on unprotected, unsaturated carbohydrates.Interestingly, ethyl acetate was found to be the solvent of choice, and the reaction proceed better if molecular sieves were omitted, since they appeared to cause unselecdve oxidation in this case (equation 13). 

The anhydro sugars were allowed to react with carbon monoxide and hydrogen (or methanol) in the same equipment used in the application of the 0X0 reaction to unsaturated carbohydrates. It was essential, however, that all reactants be anhydrous, and that the equipment be assembled in a dry-box, because traces of moisture cause hydrolysis of the anhydrides. 

Hydroformylation and deuterioformylation can also be applied to unsaturated carbohydrate derivatives142. Branched chain sugars (present in some antibiotics) are obtained as stereoiso-meric mixtures, mainly with low diastereoselectivities. From these results (using deuterated substrates) it was deduced for the first time that the oxo reaction proceeds via cis addition without direct involvement and epimerization of the asymmetric centers already present in the starting material142. 

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