Wittig olefination triphenylphosphorane

The Wittig olefination of 1,5-oxazocine 416 with [(methoxy)methylene]triphenylphosphorane led to the formation of the enol ether 431a (88% yield) as an inseparable mixture of E and Z isomers (2.5 1 ratio). Instead, when the reaction was carried out using methyltriphenylphosphorane as Wittig reagent, the as 3,5-disubstituted diastereoisomer 431b was exclusively formed in 85% yield (Scheme 84) <1998JOC3492>. 

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... 

Chiral butenolides are versatile intermediates in asymmetric synthesis. In particular, (S)-(+ )-jS-angelica lactone (260) is extremely useful for the synthesis of y-valerolactone natural products. It can be prepared in a straightforward manner by Wittig olefination of 606 with (ethoxycarbonylmethylene)triphenylphosphorane, which gives pentenoate 616 as an 82 18 mixture of Z and E isomers. After separation of the isomers by column chromatography, the desired (Z)-616 is simultaneously deprotected and lactonized by treatment with a catalytic amount of sulfuric acid to furnish 260 in nearly quantitative yield [191]. 

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). 

Ethyl 8 -apo-P"Caroten-8 -oate (1) was synthesized at an early date by Wittig olefination of the 15,15 -didehydro-C27-aldehyde 44 with 1-carbethoxyethylidene triphenylphosphorane (62) (Scheme 18). The ylide can either be isolated for use as an intermediate or generated in situ from the phosphonium salt by reaction with sodium ethoxide. The reaction is preferably carried out in dichloromethane. Exchange of this solvent for ethanol yields the 15,15 -didehydro... 

Oxoisophorone 68 can be converted into trimethylcyclohexanone (74), in a series of reduction and elimination steps [82], opening up a new route to p,p-carotene (3) and vitamin A [85,86]. The Cio-epoxide 75 can be obtained by Wittig olefination of 73 with methylene-triphenylphosphorane, isomerization and reaction with peracids. Lewis acid-catalysed rearrangement to give the five-membered ring yields the capsorubin synthon 76 [9]. 

An elegant route, directly leading to a 1 1 mixture of the two acetates 300 and 313 is reported by Anderson and Henrick 204), starting their synthesis with (1Z,5Z)-1,5-cyclooctadiene 314. Cleavage of one double bond in 314 results in the (Z)-configurated synthon 316 which, in a stereocontrolled Wittig reaction in the presence of lithium bromide and ethanol, is olefinated with the ylide pentylidene-triphenylphosphorane... 

Methyl 3- /7/-D-daunosaminide 154 has been derived from d-149 via a Wittig-type olefination using (2-thiazolylmethylene)triphenylphosphorane (Scheme 13.53). A 1 1 mixture of (E)- and (Z)-alkenes is obtained, which is isomerized in the presence of iodine into a 9 1 mixture of ( )-152 and (Z)-152. Methylation of the thiazole moiety increases the electrophilicity of the alkene, which then accepts nucleophiles such as benzylamine. The adduct is treated with NaBH4 to give a thiazolidine. Acetylation and mercury-mediated hydrolysis of the thiazolidine ring generates 153, which, on acidic treatment in methanol, yields the A-benzyl 3- /7/-D-daunosaminide 154 [99]. 

A general synthesis for all diastereomeric L-hexoses, as an example for monosaccharides that often do not occur in the chiral pool, has been worked out. The epoxidation of allylic alcohols with tertiary butyl hydroperoxide in presence of titanyl tartaric ester catalysts converts the carbon-carbon double bond stereose-lectively to a diol and is thus ideally suited for the preparation of carbohydrates. The procedure is particularly useful as a repetitive two-carbon homologiza-tion in total syntheses of higher monosaccharides and other poly hydroxy compounds. It starts with a Wittig reaction of a benzylated a-hydroxy aldehyde with (triphenylphosphoran-ylidene)acetaldehyde to produce the olefinic double bond needed for epoxidation. Reduction with sodium-borohydride... 

Z)-Allylic selenides 179 are formed in 58—69% yield under Wittig conditions using salt-free alkylidene triphenylphosphorane. A-Chlorosuccinimide/carbamate-promoted [2,3]-sig-matropic rearrangement affords allylic amines 180 in 45—64% yield. The olefin is transformed to an acid by conversion to an aldehyde followed by Jones oxidation. The resulting D-amino acids 181 are produced in 58—72% yield with enantiomeric excess values of 78—84%. 

In the first route (Scheme 101) [20], a Wittig reaction of 590 with 1-hexylidene-triphenylphosphorane gives the Z-olefin 699 in satisfactory yield. Conversion to phosphonium iodide 700 and Wittig reaction with aldehyde 701 affords methyl 12( S)-HETE (702). In this synthesis the upper aldehyde fragment and lower phosphorane fragment are joined at the -olefin. 

A short time after Wittig and Geissler had discovered the olefination of ben-zophenone with methylene triphenylphosphorane, Pommer et al. synthesized retinoic acid (3) and, soon thereafter, retinyl acetate (9), using this new C—C bond-forming synthetic procedure (Pommer, 1960, 1977 Pommer and Thieme, 1983). Thus, they laid the foundations of the BASF industrial synthesis of retinyl acetate (Reif and Grassner, 1973). 

Investigations of the Wittig reaction using a non-stabilized ylide (ethyli-dene triphenylphosphorane) (37) and various hindered aldehydes (38) under the same reaction conditions were performed in order to understand the factors which influence the stereochemistry of this process. It was experimentally shown, that the prevailing outcome toward the Z olefin is influenced only by changes in steric factors or different overcrowding in the pentacoordinated oxaphosphetane intermediates. The general reaction mechanism with nonstabilized ylides is presented in Scheme 11. 

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