Olefinations Julia-type

De Clercq [38] has utilized a sulfide linker, cleaved by a radical process initiated by electron transfer, in a solid-phase Julia-type olefination process. Alkylation of an aryl thiol resin followed by mCPBA oxidation gave supported sulfone 217 (Scheme 54). Successive treatment of the resin with n-butylhthium and an aldehyde followed by trapping of the resultant alkoxide with benzoyl chloride gave resin-bound a-benzoyloxy sulfone 218. Olefins 219 and 220 were released from the sohd support upon reduction with a single-electron-transfer reagent and elimination of the sulfone link-... 

LDA). Furthermore, Katrizky and coworkers have achieved highly stereoselective synthesis of -stilbene by reaction of tosylhydrazones with benzotriazole-stabilized carbanion with the aid of organolithium [32,33] - see (5) - X = 1 -benzotriazolyl (Bt). This method can be compared with Julia-type olefination, in which aldehyde is the substrate in the place of tosylhydrazone. 

However, reactions like this are of limited use—their success relies on the base s lack of choice of protons to attack provide an alternative H and we are back with the situation in the reaction on p. 810. Logic dictates, therefore, that only trisubstituted double bonds can be made stereospecifically in this way, because the reaction must not have a choice of hydrogen atoms to participate in the elimination. The answer is, of course, to move away from eliminations involving H, as we did with the Julia olefination. We shall look at this type of reaction for much of the rest of this chapter. 

Similarly, the C22-C26 fully substituted central tetrahydropyran ring of phorboxazole was prepared using the modified Petasis-Ferrier rearrangement. Based on the known mechanistic model, the enol acetal moiety of the rearrangement substrate required the (Z)-configuration. The synthesis of this enol ether was not possible with either the Takai- or Petasis-Tebbe oiefinations. Utilization of the Type-ll Julia olefination afforded the desired enol acetal, but with no /Z selectivity. Upon treatment of these enol ethers with Me2AICI, the rearrangement afforded only the desired tetrahydropyran in excellent yield. 

The sulfone is a versatile functional group comparable to the carbonyl functionality in its ability to activate molecules for further bond construction, the main difference between these two groups being that the sulfone is usually removed once the synthetic objective is achieved. The removal most commonly involves a reductive desulfonylation process with either replacement of the sulfone by hydrogen (Eq. 1), or a process that results in the formation of a carbon-carbon multiple bond when a P-functionalized sulfone, for example a (3-hydroxy or (3-alkoxy sulfone, is employed (Eq. 2). These types of reactions are the Julia-Lythgoe or Julia-Paris-Kocienski olefination processes. Alkylative desulfonylation (substitution of the sulfone by an alkyl group, Eq. 3), oxidative desulfonylation (Eq. 4), and substitution of the sulfone by a nucleophile (nucleophilic displacement, Eq. 5) are also known. Finally, p-eliminations (Eq. 6) or sulfur dioxide extrusion processes (Eqs. 7, 8 and 9) have become very popular for the... 

Methods for the formation of carbon-carbon double bonds in an asymmetric manner through non-Wittig-type reactions [12,13] have also been reported in recent years, including asymmetric induction by reactions with chiral sulfoxides [13], sul-fones (Julia olefination) [14], sulfoximides [12a, 15], or selenides [16] Pd-catalyzed allylic nucleophilic substitutions [17], as well as asymmetric deprotonation [18]. In the context of the topic of asymmetric carbonyl olefination, some of these asymmetric transformations are beyond the scope of this chapter, although a few of the transformations closely related to the Wittig-type reactions will be discussed in a later part of this chapter. 

The Johnson group also examined a synthesis that relied on the Julia olefin synthesis for construction of the central trisubstituted olefin. In this plan, 1 was to be prepared from an a-haloketone of type 39 via diastereoselective addition of a methyl group to the ketone, followed by a Williamson ether synthesis. Ketone 39 was to be prepared from 40 using an acetoacetic ester synthesis. Compound 40 was to be prepared from 41 using the Julia olefin synthesis. A make-or-break aspect of this plan was the stereochemical course of the Julia synthesis. Of course it was anticipated that the proper stereochemistry would result as will be seen shortly. 

Hennoxazole A displays potency against Herpes Simplex virus type 1 and peripheral analgesic activity comparable to that of indomethacin. Williams and co-workers reported a total synthesis of (-)-hennoxazole A 141. The Kocienski modification of the Julia-Lythgoe olefination was very successfully employed in the formation of Cn-Cis alkene in 85% yield with excellent iJ-selectivity E/Z = 91 9) by reacting sulfone 140 with aldehyde 139. Hydrolysis of the C4 pivaloate ester (LiOH in aqueous THF/MeOH) provided synthetic hennoxazole A (141) in 72% yield. 

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