Wittig reaction Diene synthesis

The synthesis of vitamin Dj from a sensitive dienone was another etu-ly success of phosphorus ylide synthesis (H.H. Inhoffen, 1958 A). This Wittig reaction could be carried out without any isomerization of the diene. An excess of the ylide was needed presumably because the alkoxides formed from the hydroxy group in the educt removed some of the ylide. 

The double bond transposition could also be achieved by the conversion of an intermediate for PGA2 synthesis into a 1,3-diene iron tricarbonyl complex from which PGC2 was synthesized in four steps. The Fe(CO)3 diene complex which survived the Wittig reaction was cleanly removed by Collins reagent in the subsequent step (Ref. 10). 

A useful application of the silver-mediated additions is 1,3 -diene synthesis by three-carbon elongation of aldehydes [48,51,53]. The bimetallic reagent 3-trimethylsilyl-l-propenylzirco-nocene chloride (A Scheme 8.23) reacts with aldehydes under the influence of a catalytic amount of Ag+ to give the intermediate zirconocene-alkoxide B, which then undergoes a Peterson-type 1,4-elimination of TMS alkoxide to stereoselectively afford ( )-dienes (fc/Z > 96 4) (Scheme 8.23). A Wittig reaction yields the same products without stereoselectivity (ca. 1 1 mixtures of E- and Z-isomers). 

The Wittig reaction was employed to fuse diene 49 and aldehyde 50, in the final stages of the stereoselective synthesis of epothilone B, a macrocyclic compound with potential antifungal properties (equation 31)49. 

Subsequent monosilylation and Wittig reaction furnished unsymmetrical double diene 170. The synthesis of the other Diels-Alder partner started from bromophenol 173 (prepared in three steps from dimethoxytoluene), which was doubly metalated and reacted with (S,S)-menthylp-toluenesulfinate 173. CAN oxidation delivered quinone 171, which underwent a Diels-Alder reaction with double diene 170 to give compound 175 possessing the correct regio- and stereochemistry. Upon heating in toluene the desired elimination occurred followed by IMDA reaction to adduct 176, which was obtained in an excellent yield and enantioselectivity. Both Diels-Alder reactions proceeded through an endo transition state the enantioselectivity of the first cyclization is due to the chiral auxiliary, which favors an endo approach of 170 to the sterically less congested face (top face) (Scheme 27). 

The second synthesis of 654 and 655 makes use350,351 of the Wittig reaction. The (methylthio)methyl ether 656 is converted into the chloromethyl ether 657, which reacts with triphenylphosphine to yield a crystalline phosphonium salt (658). Reaction of 658 with phenyllithium gives a phosphorane, treatment of which with acryl-aldehyde leads to ethers 654 and 655 in —50% yield. Pure trtms-diene 654 was obtained352 in a reversed way consisting in preparation of a sugar ether acrylaldehyde (660) by replacement of the p-tolylsulfonyl group in 659, followed by reaction of 660 with methylenetriphenyl-phosphorane. 

Some Japanese chemists needed the E,E-diene below for a synthesis of a neurotoxic compound that they had isolated from poison dart frogs. Unfortunately, their synthesis (which used a Wittig reaction—Chapter 14 and later in this chapter) gave only 4 1 E selectivity at one of the double bonds. To produce pure E,E-diene, they equilibrated the ,Z-diene to , by treating with iodine and irradiating with a sun-lamp. 

This procedure has been utilized by Nicolaou to prepare the vinyl iodide (482) in the synthesis of lipo-toxins As and Bs (equation 111). The synthesis of vinyl iodides was also utilized by Bestmann in a stereospecific synthesis of (4 ,6 ,llZ)-hexadecatrienal. A Wittig reaction was used to create the ( )-al-kene (484), and the ( )-diene portion was synthesized via vinyl iodide (485) formation and coupling (Scheme 63). This method has been applied to the synthesis of > C-labeled vinyl iodide (488 equation 112). Labeled iodoform (486) was ma and the reaction conditions altered fhrni those employed by Takai and cowmkers in order to use smaller quantities of the valuable iodoform, relative to C1CI2. 

The female silkworm moth attracts mates by producing a pheromone known as bombykol. Bombykol is an ,Z-diene, and in this synthesis (datingfrom 1977) two successive Wittig reactions exploit the stereoselectivity obtained with... 

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