Julia reaction

Nucleophilic additions to carbonyl groups lead to alcohols which on dehydration, furnish alkenes70,71. This two-step protocol has been extremely useful for diene and polyene synthesis with wide variation in the carbonyl substrate and the nucleophilic addendum. Diene synthesis using aldol-type condensation as well as phenyl sulphonyl carbanion (the Julia reaction) are also discussed in this section. 

Making alkenes by addition to alkynes offers two distinct advantages. Firstly, although the reaction is not connective in the sense that the Wittig and Julia reactions are, the starting materials can often be made straightforwardly by alkylation of alkynyl anions. Secondly, the same alkyne can be used to make either E- or Z-alkene—an advantage shared with the Peterson reaction but here the... 

The olefination based upon the reaction of benzothiazolyl- and phenyltetra-zolyl sulfones with carbonyl compounds is widely used in the target-oriented synthesis. In order to illustrate the reaction scope, yields and stereoselectivities, in this section we present selected examples of these reactions. The examples include reactions of saturated sulfones with saturated aldehydes, saturated sulfones with o, j6-unsaturated carbonyl compounds, -unsaturated sulfones with saturated aldehydes, and /l,y-imsaturated sulfones with a, -unsaturated aldehydes. The emphasis is given to recent work. A complete account of earlier applications of the modified Julia reaction has been given in the Blakemore review [98]. 

In a study on vitamin D2 synthesis [ 124], a sterically very hindered sulfone 273 (Scheme 90) with the axially oriented sulfonyl group was transformed into an anion (NaHMDS) and subjected to reaction with diene-aldehyde 274 used in excess. After deprotection, vitamin D2 275 and its unstable C7-C8 Z-isomer 276, were obtained in 70% yield, ratio of 72/28, respectively. Some BT-sulfone 277 generated by epimerization of 273 was also isolated. An attempt to carry out the reaction with the reverse allotment of the fimctional groups (sulfone 278 with ketone 279) failed. With regard to the isomer ratio 275 and 276, it is of interest that the classical Julia reaction of phenylsuhbne corresponding to 277 and aldehyde 274 occurs with somewhat lower selectivity towards the -isomer [125]. 

The first is a Wittig reaction with an unstabilized ylid, the second a Julia reaction, and the last two are Peterson reactions under different conditions. Each reaction is described in detail in the chapter. The Wittig reaction is under kinetic control and is a stereospecifically cis elimination. In this case the product is the Z-alkene. 

The Julia reaction is under thermodynamic control as the equilibration occurs under the reaction conditions. The product, formed stereoselectively, is the -alkene. 

Williams carried out a Julia coupling similar to the Keck example. With the removal of the acetal functionality, the coupling step of the Julia reaction was efficient, but the usual reductive elimination procedure failed. As an alternative to the acetylation and reductive elimination procedure, the P-sulfo-nyl xanthate was formed by quenching the addition reaction with carbon disulfide and methyl iodide. Reductive elimination was then carried out with tri-n-butyltin hydride to yield the desired ( )-alkene (399) in an 85 15 ratio with the (Z)-alkene in 83% overall yield (equation 91). 

As discussed in Section 3.1.11.1, which covers the reductive cleavage of the 3-hydroxy sulfone derivatives to alkenes, the Julia reaction proceeds by the formation of an anion that is able to equilibrate to the thermodynamic mixture prior to elimination. Therefore, there is no inherent advantage in producing the erthyro- or threo-fi-hydroxy sulfone selectively fix>m the keto sulfone. The ( )/(Z)-mixture of alkenes should be the same. This method is used to produce alkenes in cases where the acid derivative is more readily available or more reactive. The reaction of the sulfone anion with esters to form the keto sulfone, followed by reduction with metal hydrides has been studied. The steric effects in the reduction do become important for the reaction to produce vinyl sulfones, which are formed from the anti elimination of the 3-hydroxy sulfone adduct, as mentioned in Section 3.1.11.6.2. Some examples of the use of esters are presented below. 

Dumeunier, R., Marko, I. E. The Julia reaction. Modern Carbonyl Olefination 2004,104-150. 

Sulfonyl carbanions undergo aldol-type reactions with aldehydes and ketones to give p-hydroxy sulfones which can be converted into alkenes (the Julia reaction) (see Chapter 10, p. 197). With allyl methyl sulfones (75) and a,p-unsaturated carbonyl compounds (63),... 

In certain cases, direct elimination of the hydroxysulfone (86) is effective, but generally it is better to go via the acyl derivative (88) which is formed in situ. The Julia reaction essentially resembles the Wittig and Peterson reactions, in that an a-heteroatom-substituted carbanion and a carbonyl compound react together with the subsequent elimination of two vicinal functional groups to form the... 

The generally accepted mechanism of the Ramberg-Backlund reaction (Scheme 39) involves the deprotonation of the a-chlorosulfone by the base to give the sulfonyl carbanion (92). The latter undergoes an intramolecular nucleophilic attack on the a-carbon atom with elimination of the chloride anion and formation of the episulfone (93), which is unstable and extrudes sulfur dioxide to yield the alkene (Scheme 39).6 The Ramberg-Backlund reaction, unlike the Julia reaction, yields mainly the (Z)-alkene from acyclic starting materials. 

Modified Julia reactions The Kocienski modification of the Julia reaction Direct Coupling of Carbonyl Compounds and Alkenes... 

Recent developments emphasise the convenience of replacing the three step (Marc) Julia reaction by one-step procedures using reagents 147 in which Ar is a heterocycle. Thus (Sylvestre) Julia used a benzothiazole 157. The adduct 158 with an aldehyde decomposes by fragmentation of the spiro compound 159 without the need for any further reagents to give S02, the alkene 150 and the benzothiazole 169. The benzene rings are omitted from 158-160 for clarity.31... 

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