Silyl-Protected Tartaric Acids

The commercial availability of numerous silyl chlorides, the ease of their attachment, and their selectivity toward removal under mild conditions, makes silyl protection extremely attractive. 

The spatial bulk of vicinal er butyldimethylsilyloxy protection exerts a significant role in controlling rotational isomeric population. Diethyl (4iS, 5 S)-4,5-bis( 6r -butyldimethylsilyl-oxy)-(2 , 6.E)-octadienedioate (694), prepared from 24 [18] by acidic deprotection followed by reprotection with fer butyldimethylsilyl triflate in the presence of triethylamine [211], exists as the conformer 695 even at room temperature. Nucleophilic attack at the jS-carbon of the enoate moiety of 695 should occur only toward the two Ti-faces, which are exposed to the outside of the molecule. Michael addition of several Grignard reagent-cuprous iodide mixtures (1 1) results in the isolation of a single enantiomer 696a-d in every case. 

The Diels-Alder reaction of 694 with cyclopentadiene is a relatively slow process that proceeds to give in 90% the single product 705, where only one outside face undergoes the cycloaddition reaction. Cyclopropanation of 694 with isopropylidenetriphenylphosphorane does not take place, presumably due to steric crowding [212]. 

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The Swern conditions were applied to a number of substrates with different functional and protecting groups, such as sugar derivatives, protected amino acid derivatives, tartaric acid derivatives, and optically active synthetic intermediates. Both acid-sensitive (epoxide, acetonide, silyl, NBoc, NCBz) and alkaline-sensitive groups (Ac, Bz, ester, silyl) were found to be completely unaffected. The proposed mechanism begins with tautomerisation of the amide to the hydroxy imine, followed by reaction with the dimethylchlorosulfonium species. The resulting oxysulfonium species 63 collapses when treated with base to regenerate DMSO and produce the nitrile. 

The diversity associated with silyl protecting groups as well as the chemical conditions available for their removal makes them attractive alternatives to benzyl protection of the hydroxy groups of either D- or L-tartaric acid derivatives. O-isopropylidene-L-threitol (37) is mono-protected with er -butyldimethylsilyl chloride to furnish 266, which is converted in three steps to the nitrile 267. Reduction with DIBAL and Wittig olefination followed by desilylation with fluoride and Swern oxidation of the resulting alcohol provides aldehyde 268, which reacts with methyl 10-(triphenylphosphorane)-9-oxo-decanoate (269) to afford enone 270. Reduction of 270 with subsequent preparative TLC and acetal hydrolysis furnishes (9R)-271 and (9 S)-272, both interesting unsaturated trihydroxy Cig fatty acid metabolites isolated from vegetables [91] (Scheme 62). 

The protected butane-1,2,3,4-tetraol 15, easily available in three steps from D-tartaric add diethyl ester, was the starting material for the synthesis of (+)-phomopsohde B (Scheme 2.4). Thus, IBX (2-iodoxybenzoic acid) oxidation of the primary alcohol followed by HWE olefination with a chiral phosphonate derived from L-lactic add (not depicted) gave a,fi-enone 16. Stereoselective reduction of the ketone carbonyl and acidic deavage of the acetal moiety furnished triol 17. Selective protection of the two secondary hydroxyl groups was achieved through triple silylation with subsequent selective desilylation of the primary OTBS group. 

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