Esters Julia coupling

Heliannuols are not an exception. Only one year later following the publication of heliannuol A, the first total synthesis of the racemic (+)-heliannuol A using the coumarin 18 as starting material was published.7 A key step in this synthesis was the ring closure achieved by two different methods intramolecular Julia coupling of the sulfone 19 and sulfone ester cyclization of the alternative sulfone 20 (Fig. 5.4.A). Desulfonation and demethylation yielded the desired (+)-heliannuol A. 

An interesting intramolecular iq>plication of the Julia coupling through an ester was carried out by Kang and coworkers in the total synthesis of trinoranastreptene (458 Scheme 60). The reduction produced isomeric alcohols, which were separated by chromatography. The major isomer was carried through the sequence shown in Scheme 60, while the minor isomer was resistant to functionalization. 

After l.S- yn-selective reduction with NaBH4-Et2BOMe, the ester 336 was converted into 338 via lactone 337 through further functional group manipulation. The Julia coupling of 338 and aldehyde 339 followed by 3 elimination gave 340, which was converted into methoxymethyl ketone 341 in straightforward steps. 

In its original form,94 the Julia reaction consisted of the formation of a carbon-carbon double bond through the coupling of a sulfonyl-stabilized anion and a carbonyl compound to generate a P-hydroxy sulfone, followed by a reductive elimination to afford the alkene (Eq. 47). A subsequent study of its scope and stereochemistry led to improved reaction conditions, which are now widely used.206 Alternative methods to synthesize the P-hydroxy sulfone intermediates, such as the addition of sulfonyl carbanions to esters with subsequent reduction of the ketone to the P-hydroxy sulfone, are also known (Eq. 121).207... 

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