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126 Scheme 27

The same group also courageously discovered that the reaction of sugar lactones with the stabilized ylide 125 under high-temperature sealed-tube conditions gives good yields of the corresponding Wittig products (Scheme 27)! No mechanistic explanation is offered, but the sealed-tube conditions are crucial for success. No reaction occurs if the products are heated under reflux at similar temperatures under atmospheric pressure [37]. When the same reaction was carried out on sugar lactones that had a judiciously placed free hydroxyl, cyclized structures were obtained. For example, reaction of 126 with 125 gave a 1:1 mixture of 127 and 128. Compound 127 results from Michael addition of the free hydroxyl addition onto the a,^-unsat-urated ester function (Scheme 27) [38].

C. Wittig Reaction with Unstabilized Ylides Followed by Cyclization

The Wittig reaction of a sugar lactol with an unstabilized ylide to give a hydroxy olefin poised to undergo electrophilic-induced cyclization is a common method for the preparation of C-glycosides. Martin et al. converted 129 to olefin 130 and followed this by inversion and introduction of the nitrogen substituent to give 131. Mercury-induced cyclization was followed by treatment with iodine to give compound 132. Presumably the benzyl carbamate participates to form a new C—O bond during the treatment of the organomercurial intermediate with iodine. Compound 132 could also be debenzylated and treated with base go give 133, the a homoanalog of galactostatin. Alternatively, 132 was transformed into 134, and exposure to potassium carbonate then gave 135, the 1,N-anhydro derivative, a potential inhibitor of both a- and ^-galactosidases, (Scheme 28) [39].

Work from the same group showed that olefin 137, available via Wittig reaction of 136, could be reductively aminated to give a mixture of amines 138 and 139 in a 5:2 ratio (Scheme 29). NIS promoted cyclization of 138, and 139 then gave 140 and 141, respectively, in good yield. Similar chemistry was carried out in the galacto series [40].

Scheme 28

Nicotra et al. observed that 144 or 145, obtained by mercury-induced cycli-zation of 142 and 143, could not be converted to the desired iodo compound 146. The workers had to resort to introducing the 2-deoxynitrogen substituent after the phosphonate had been introduced as shown in Scheme 30. The ketone was converted to an oxime and with diborane gave the gluco isomer 149 in 64% diastereomeric excess [41].

Schmidt et al. also used electrophilic cyclization to gain access to C-glycosides, in this instance to produce 2-deoxy C-aryl glycosides. Known aldehyde 150 was olefinated and gave a mixture of isomeric olefins 151, which were converted to 152 and 153 and separated. Compounds 153a-c and 152c were exposed to NIS in ace-tonitrile and gave good yields of the /3 isomers exclusively. Protecting group manipulation and removal of the iodine atom then gave the ^-C-aryl glycosides 155a-c (Scheme 31) [42].

Work by Tius has shown that the preference for formation of the axial organ-omercurial is not due solely to coordination of the incoming mercurio species to the C2 oxygen substituent. Oxymercuration of 156, a compound in which there is no C2 substituent, gave a 60:40 ratio of 157 and 158, respectively. Interestingly enough, cyclization of the TBS derivative 159 gave 160 as the exclusive product (Scheme 32). Compound 160 was transformed into the known triacetate 162 by standard methods. The axial OTBS groups and equatorial methyl group are preferred because van der Waals repulsions that occur between the OTBS groups when they are equatorial are of greater energy than the 1,3-diaxial interactions that occur when the groups are disposed axially [43].

Hydroxy olefin 164 was epoxidized with mCPBA to give a mixture of C-glycosides 165 and 166 in the yields shown in Scheme 33. Compound 165 then served as a building block for C-nucleoside synthesis [44]. Two groups reported a novel cyclization reaction when a suitably protected sugar derivative was treated with triflic anhydride in the presence of pyridine. Thus, exposure of 136 to the aforementioned conditions gave an excellent yield of the vinyl C-furanoside 169. Several other sugars were examined, and all gave good yields of the corresponding furanosides. The reaction proceeds via triflation of the free hydroxyl group to give 167, and displacement with the C3 benzyloxy group provided 168, which is then debenzylated to deliver 169 [45,46]. Sharma and coworkers found that exposure of

Scheme 29

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