Reduction phosphonium ylide synthesis

With the fully functionalized heterocyclic core completed, synthetic attention next focused on introduction of the 3,5-dihydroxyheptanoic acid side-chain. This required initial conversion of the ethyl ester of 35 to the corresponding aldehyde through a two-step reduction/oxidation sequence. In that event, a low-temperature DIBAL reduction of 35 provided primary alcohol 36, which was then oxidized to aldehyde 37 with TRAP. Subsequent installation of the carbon backbone of the side-chain was accomplished using a Wittig olefination reaction with stabilized phosphonium ylide 38 resulting in exclusive formation of the desired -olefin 39. The synthesis of phosphonium ylide 38 will be examined in Scheme 12.5 (Konoike and Araki, 1994). 

The cyclohexanone (S3), an intermediate for the synthesis of thromboxane antagonists, has been prepared by a combination of phosphine oxide- and phosphonium ylide-based olefinations.30 Reaction of the lactone (50) with methoxymethyldiphenylphosphine oxide anion gave a poorly characterized adduct (presumably (51)) which on reduction with sodium borohydride, followed by treatment with sodium hydride gave the vinyl ether (52) in 80% overall yield from (SO) (Scheme 8). Further modification gave the required cyclohexanone (53). 

Axelrod et alP have describe the synthesis of 1,5-dienes by alkylation of an allylic phosphonium ylide with an allylic bromide. The method was used to synthesize pure all-( )-squalene from ( , )-fame-syl bromide and its tributylphosphonium salt. No isomerization occurred during the reaction and reduction of the resulting phosphonium salt with lithium in ethylamine gave squalene in 65% yield. 

In an attempt to increase the Wittig-type reactivity of amide derivatives the reaction of phosphonium ylides, e.g. (91), with thioimides, e.g. (92) and (93), has been investigated.49 Although the thio-Wittig reaction takes place, S-alkylation and oxidation-reduction occur in competition and reduce the usefulness of this reaction in synthesis. Further studies of the reactions of a-perfluoroacylalkylphosphonium salt (94),50.51 generated by... 

The enantioselective synthesis of a somewhat more complex renin inhibitor starts with the reduction of the ester group in the chiral amino-ester (19-1) by means of diisobutyl aluminum hydride in the cold. The aldehyde product (19-2) is then reacted with prior isolation with the ylide from phosphonium salt (19-3) and a strong base... 

For the synthesis of 313 Hammond and Descoins also used a Wittig reaction 205). Thus, starting from l-hepten-3-ol 319 the phosphonium salt 320 is formed via several steps. The ylide of this salt is olefinated with atdehyde 305 to 311. Reduction of 311 and subsequent acetylation afford the pheromone 313 (Scheme 58) 205). 

Sodium amalgam-reduction of the salt (69) (obtained from the reaction of acyl-stabilized ylides with trifluoromethane sulphonic anhydride) provides a new synthesis of acetylenes (Scheme 11). A new synthesis of ethynyltriphenyl-phosphonium salts (70) is provided by the reaction of acylmethylenetriphenyl-phosphoranes with dibromotriphenylphosphorane and base. ... 

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