Silyl-Wittig olefination

The 9 — 15 fragment was prepared by a similar route. Once again Sharpless kinetic resolution method was applied, but in the opposite sense, i.e., at 29% conversion a mixture of the racemic olefin educt with the virtually pure epoxide stereoisomer was obtained. On acid-catalysed epoxide opening and lactonization the stereocentre C-12 was inverted, and the pure dihydroxy lactone was isolated. This was methylated, protected as the acetonide, reduced to the lactol, protected by Wittig olefination and silylation, and finally ozonolysed to give the desired aldehyde. 

Whereas the nucleophilic addition of vinylmagnesium bromide to a-alkoxy aldehydes (12, 16) proceeds with a low to moderate chelation-controlled diastereoselectivity, a remarkably high preference for the opposite stereochemical behavior is found with the jS-silyl phosphorus ylide 1477. Due to the electron-donating 4-methoxyphenyl substituents at the phosphorus atom, as well as the /i-methyldiphenylsilyl group, 14 is an excellent vinylation reagent which does not lead to any Wittig olefination products. 

Peterson Olefination Reaction (Peterson Elimination, Silyl-Wittig Reaction) The Reaction ... 

Wittig olefination reaction ( the phosphorus way ) has been a very popular reaction in organic synthesis. However, it is now in competition with Peterson/Chan olefination reaction327 ( the silicon way ). Formally, this latter involves the formation of a (3-silyl heteroatomic anion, which in the absence of an electrophile undergoes a (3-shift of the silyl moiety to the heteroatom (usually oxygen) with final elimination of silylated heteroatomic anion and formation of the olefin. 

A keto group was extensively used in olefinations, providing a convenient access to natural-type oxonine products. Chemoselective formation of silyl enol ether of oxonine 171 (Scheme 34) followed by Wittig olefination, deprotection, and diastereoselective methylation afforded acetate 172 in good yield <2004JA1642>. 

In a very similar manner, (l-silylcyclopropyl)lithiums can be used to alkylate a-selanyl aldehydes and the products subjected to dehydroxyselenation to give alkenyl(silyl)cyclopropanes. Here, too, the f-isomer is obtained in contrast to the Z orientation in the Wittig olefination of the corresponding 1-silylcyclopropanecarbaldehydes. Thus, l-[( )-oct-l-enyl]-l-(trimethylsilyl)cy-clopropane (8) was obtained in 79% yield from the corresponding hydroxy silyl selenide 7. 

Wittig olefinations continue to be exploited for the synthesis of heterocyclic species. For example, acylphosphoranes (65), formed as intermediates in the condensation of (trimethylsilyl)methylenetriphenylphosphorane and the silyl esters of 0-acyl(aroyl)salicylic acids, undergo intramolecular Wittig reactions producing substituted chromenones (66) (Scheme 14). " Treatment of diox-olanones (67) with (carbethoxymethylene)triphenylphosphorane produces the corresponding a,p-unsaturated esters (68), which are useful precursors to... 

The total synthesis of ( )-trichostatin A has been carried out by two routes [67] one uses the y-alkylation of a silyl dienol ether with an acetal which gives the ether in a Mukaiyama reaction. A Wittig olefination followed by DDQ oxidation gives a ketoester which reacts with hydroxylamine to give trichostatin A in 22% overall yield (Scheme 20). 

Chiral allylic acetates 426 can be prepared using a similar j5-ketophosphonate (425), also derived from lactic acid. The desired 425 is formed via reaction of lithiated diphenylphos-phonate with 401. Reduction of the ketone gives an intermediate alcohol which, upon treatment with base, forms the ( )-Wittig olefin. Removal of the silyl protecting group followed by acetylation gives the product 426 (> 98% ee) [133]. 

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). 

As outlined in Scheme 6, isovanillin (35) was converted to aryl iodide 36 via MOM-protection, protection of the aldehyde, and subsequent iodination. Hydrolysis of the acetal and Wittig olefination delivered phenol 37 after exposure of the intermediate aldehyde to methanolic hydrochloric acid. Epoxide 41, the coupling partner of phenol 37 in the key Tsuji-Trost-reaction, was synthesized from benzoic acid following a procedure developed by Fukuyama for the synthesis of strychnine [62]. Birch reduction of benzoic acid with subsequent isomerization of one double bond into conjugation was followed by esterification and bromohydrin formation (40). The ester was reduced and the bromohydrin was treated with base to provide the epoxide. Silylation concluded the preparation of epoxide 41, the coupling partner for iodide 37, and both fragments were reacted in the presence of palladium to attain iodide 38. 

Allylsilanes can be prepared by a wide array of methods, including (1) the reaction of allyl metals with ClSiRs, (2) the reaction of silylanions (MSiRs) with allylic substrates, (3) the Kumada coupling of Me3SiCH2MgBr with vinyl halides, catalyzed by Pd or Ni species, (4) the Wittig reaction of P-silylated Wittig reagents, (5) the cross-metathesis of olefins with allylsilanes, and (6) the reductive silylation of unsaturated compounds. ... 

The phosphorus ylides of the Wittig reaction can be replaced by trimethylsilylmethyl-carbanions (Peterson reaction). These silylated carbanions add to carbonyl groups and can easily be eliminated with base to give olefins. The only by-products are volatile silanols. They are more easily removed than the phosphine oxides or phosphates of the more conventional Wittig or Homer reactions (D.J. Peterson, 1968). 

---