Julia-synthesis

Interestingly, when a fi-substituted alcohol is used in the Barton-McCombie reaction and if a [3-elimination process occurs faster than the hydrogen transfer step, then the formation of a double bond is observed. We have just seen such an example with a dixanthate (see Section 3.1.3). Many others are known as in [3-hydroxy sulfides [231] and [3-hydroxysulfones [232,233] in a modified Julia synthesis of olefins. 

Alkene synthesis.9 The key step in the Julia synthesis of alkenes (11, 473-475) involves reductive elimination of a P-hydroxy sulfone with sodium amalgam. A recent modification involves elimination of a p-hydroxy imidazolyl sulfone with Sml2 (equation I).1 Both syntheses are particularly useful for preparation of disubstituted alkenes and conjugated dienes and trienes. Both methods of elimination favor formation of (E)-alkenes. In a direct comparison, a higher yield was obtained with Sml2 than with Na(Hg). 

Allylic alcohols from sulfones.1 Polish chemists have extended the Julia synthesis of alkenes (11, 474) to a synthesis of allylic alcohols. In the presence of 1 equiv. of BF3 etherate, a-alkoxy aldehydes react with lithiafed sulfones to form adducts that are converted to allylic alcohols on reduction with sodium amalgam. This reaction was developed specifically for a synthesis of prostaglandins from Corey s lactone-aldehyde, but should have wider application. 

A group of scientists of the Agricultural Research Service of the USDA in Beltsville reported two syntheses of JH1 170, the second of which (Scheme 33) included a Wittig olefmation. 4-Methylhex-(J5)-3-enyl bromide 187, obtained from 186 via Julia synthesis, was reacted with propylidenephosphorane 188 to yield 189143). Carbonyl olefmation of 189 with aldehyde 190 gave the 2,6,10-alkatrienoic ester 191 which represents a precursor of JH11441 (Scheme 33). 

This rearrangement also occurs in the Julia synthesis of homoallyl bromides starting with easily available cyclopropylmethyl alcohols (equation 18) These bromides are versatile electrophiles and have been involved as building blocks in many natural product preparations ". ... 

While special cases might be imagined where dehydration could favor one alkene rather than another, the situation depicted for cyclohexanone in Scheme 9.74 is typical. Aldehydes generally behave similarly with the potential for dehydration of the alcohol generated by the addition routinely realized. However, utilizing P-acyloxysulfones (the Julia synthesis) regioselective double bond introduction is possible. 

Scheme 9.75. A generalized description of the Julia synthesis in which trans- or fisj-alkenes are preferentially formed. In this case, cyclohexanone is converted into a substituted alkene, which eventually produces an anion capable of attacking benzenecarboxaldehyde (benzal-dehyde). Although both diasteriomers are (apparently) produced, ehmination generates only the ( )-alkene.

Deoxy-2 -difluoromethylene nucleosides, also of interest in connection with the inhibition of ribonucleotide diphosphate reductase, have been made by a modified Julia synthesis as outlined in Scheme 13 the cytosine analogue was also reported. 0 OEt... 

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. 

---