Second Generation Julia Reactions

In 1991, Sylvestre Julia reported a direct synthesis of olefins from carbonyl compounds and lithiated heterocyclic sulfones [132-134]. After the initial coupling 

At the start of this work, the dual nucleophilic-electrophilic character of the a-sulfonyl carbanion 213 created some problems since this anion could react not only with the carbonyl derivative (aldehyde or ketone) but also with itself, generating via this competitive pathway some homocoupling by-products. However, a wise selection of the sulfone electrophilic substituent and the use of Barbier-type conditions considerably increased the chemoselectivity of the addition reaction and directed the addition onto the carbonyl function. Benzothiazole derivatives (hereafter denoted BT) were the first substrates to be utilized in this process. After some fine tuning, they proved to be suitable candidates, affording the desired alkenes with a reasonable efficiency (Table 3.11). 

Sylvestre Julia and co-workers also found that the two diastereoisomers of the -hydroxy-BT-sulfones underwent elimination at different rates. The syn-isomer afforded the (Z)-alkene much faster than the anti-diastereoisomer produced the corresponding ( )-alkene. As can be seen in species 220 and 221, and are in an anti relationship during the transfer of the BT moiety of 218b. Further rotation about the central C-C bond is required to position the -OBT and -SO2 groups 

Julia et al. also noticed that the use of prenyl- or benzyl-BT-sulfones afforded the olefin products with reduced stereocontrol. This lower selectivity was rationalized 

Five years later, in 1996, Kociensky ef a. successfully applied this methodology in their synthetic approach to Rapamycin [135]. They took advantage of the aforementioned observations that stabilized BT-sulfonyl a-carbanions favored -selective olefination. However, when they performed the coupling of enal 227 with the meta- 

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Scheme 3.42. Mechanism of the second-generation Julia reactions.

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