Phenols, reaction with glycals

The reaction of 2-C-hydroxymethyl glycals with phenols or phthalimide under Mitsunobu conditions to produce 2-C-methylene glycosides has been reported (See Vol. 27, p. 178, ref. 51 for the same reaction under Lewis acid conditions). The condensation of malononitrile and methyl 4,6-( -benzylidene-3-deoxy-a-D-crytAro-hexopyranoside-2-ulose under basic conditions affords the corresponding methyl 4,6-0-benzylidene-2-(dicyanomethylene)-2,3-dideoxy-a-D-eryt/iro-hexo-pyranoside. This latter compound on reaction with 3-benzyl-2-methylthio-2-thiazolinium iodide affords butadiene 58 whilst with 3-benzyl-4,5-dihydro-2-methylthio-l,3-thiazinium iodide, 59 is produced. ... 

The glycals react with water, alcohols, phenols, carboxylic acids, and certain bases, in the presence of an acidic catalyst, in the same way as does 2,3-dihydro-4/f-pyran (which gives, for example, 2-hydroxy-, 2-alkoxy-, and 2-aryloxy-tetrahydropyrans in high yield ). (Tetrahydro-pyranyl ethers are useful for protecting alcoholic groupings during reactions in basic media, and are readily hydrolyzed with acid,) The first step of these additions would be expected to be protonation at C-2, followed by attack of the nucleophilic reagent on the resonance-stabilized, C-1 carbonium ion. 

Alkylations. The reagent effects reductive Af-alkylation of A -tosylamines and indole derivatives with alcohols. The Mitsunobu reaction of 2-(l-hydroxy-alkyl)-acrylic esters and that of glycals with phenols follow an Sn2 course. The reaction has been applied to the inversion of configuration at an a-cyanohydrin center, whereas alkyl nitriles are prepared by this method using acetonitrile cyanohydrin as the source of nucleophile. The C-alkylation of o-nitroarylacetonitriles at the ben-zylic position is easily controlled. 

Silylated glycals react with benzoquinone in the presence of r-butyllithium to produce C-1-benzo-quinol glycals which can be reduced with sodium dithionite to C-l-p-hydroxyaryl glycals. An unexpected preparation of C-3-aryl-3-deoxy-glycals has been discovered during an attempt to add phenols by acid-catalyzed Michael reaction applied to C-2-formyl glycals. ... 

Aryl 2,3-unsaturated 0-glycosides also result from the reaction of unsubstituted glycals with phenols in the presence of diethyl azodicarboxylate and tri-phenylphosphine, some reactions affording the products in high yields and with stereospecific introduction of the aglycone. In this way, the p-methoxyphenyl 2,3-unsaturated a-glycoside is obtained in 80% yield from L-rhamnal using dichloromethane as solvent [55]. 

The glycosidic bonds present in KS-502 and rebeccamycin provided especially attractive contexts for evaluation of the glycal epoxide method (Scheme 13). Treatment of the furanose glycal with DMDO gave the furanose epoxide 69 ster-eoselectively [38]. Reaction of this epoxide with the phenol 70 afforded an 81% yield of the desired aryl-glycoside 71. Subsequent steps completed the synthesis of KS-501 (42) and KS-502 (43). These furanoid epoxides were also used in the synthesis of nucleosides [39]. 

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