Coupling Julia

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. 

Completion of the total synthesis of clavepictines A and B is shown in Scheme 10. Conversion of 18 to the alcohol 19 via 4 steps and reduction of the hydroxyl group in 19 via iodide gave the quinolizidine 20. Finally, the dienyl moiety was constructed by Julia coupling, and deprotection furnished clavepictine B. Acetylation of the hydroxyl group of clavepictine B gave clavepictine A. 

Give an explanation for the preferential formation of the (3-epimer in the Julia coupling j. 

A small amount of compound 7 was isolated from the Julia coupling. Give an explanation for its formation. 

A study carried out by Kocienski and Lythgoe flrst demonstrated the trans selectivity of the Julia coupling process. The authors found the i uctive elimination could best be carried out with the acet-oxy or benzoyloxy sulfones. If the lithio sulfone derivative is used for addition to the carbonyl, the reaction can be worked up with acetic anhydride or benzoyl chloride to obtain the alkene precursor. In cases where enolization of the carbonyl is a complication, the magnesium derivative can frequently be used successfully. A modification of the reductive elimination was found to be most effective. Methanol, ethyl acetate/methanol or THF/methanol were the solvents of choice and a temperature of -20 C was effective at suppressing the undesired elimination of the acetoxy group to produce the vinyl sulfone. With these modifications of the original procedure, the ability of the reaction to produce dienes as well as rran.r-disubstituted alkenes was demonstrated, llie diastereoisomeric erythro- and threo-acetoxy sulfones could be separated and it was demonstrated that both isomers were converted to the rrans-alkene. It... 

The Julia coupling can be utilized as an alternative to the Schlosser-Wittig reaction to form ( )-al-kenes. Several reported syntheses of pseudomonic acid C (385) have provided interesting clues as to variability of tq)plications of the Julia coupling in the context of natural product synthesis. 

The ( )-disubstituted alkene has been extensively studied with several applications of the Julia coupling attempted. The first synthesis of the natural product was accomplish by Kozikowski. In tltis t roach, the aldehyde (386) was reacted with 2 equiv. of the Wittig reagent (387) to produce (388), with an ( ) (Z) ratio of 40 (equation 89 no yield given). This first synthesis establishes the baseline... 

Keck attempted to apply the Julia coupling to the synthesis of pseudomonic acid Despite the success of the sulfone (393) in reactions with simple aldehydes, only modest yields of the desired coupling were observed. This problem was solved by reversing the aldehyde (395) and sulfone components (394), as shown in Scheme 55. The anion was formed with LDA in THF and condensed with the aldehyde. The P-hydroxysulfone was converted to the mesylate, and the reduction and simultaneous deprotection of the benzylglycoside was carried out with lithium and ammonia to produce the ( )-alkene (396), in 37% overall yield with excellent selectivity. 

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