Modified Julia Olefination Julia-Kocienski Olefination The Modified Julia Olefination enables the preparation of alkenes from benzothiazolyl sulfones and aldehydes in a single step: The Julia-Kochienski Olefination - a further refinement of the Modified Julia Olefination - offers very good E-selectivity. Mechanisms of Modified Julia Olefinations The initial addition of the sulfonyl anion to the aldehyde is not reversible: Whether the anti or syn intermediate is generated can be influenced to some extent by the choice of reaction conditions: A chelate will form with small counterions Li and in apolar solvents, leading to a closed transition state. With larger counterions K and polar solvents, an open transition state becomes possible. The intermediates that form react further to give E- and Z-isomers of the alkene: A mechanistically related nucleophilic addition of the sulfonyl carbanion to a second equivalent of the BT sulfone leads to a side product. The benzothiazolyl group BT can play several roles: in one, it enables a more or less strongly pronounced complexation that influences the selectivity; on the other hand, it can also undergo nucleophilic substitution at the carbon attached to the sulfonyl group, which then becomes a leaving group.
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Julia-Lythgoe Olefination This multistep synthesis enables the preparation of E -alkenes. The addition of a phenylsulfonyl carbanion to an aldehyde or ketone leads to an intermediate alcohol, which is esterified in situ.
The reductive elimination with sodium amalgam to furnish the alkene takes place in a second step. The Julia-Kociensky Olefination is an alternative procedure, which leads to the olefin in one step. Mechanism of the Julia Olefination The acetoxysulfone synthesis produces diastereomers: A first possible mechanism proceeds through a planar radical that can rotate freely about the C-C bond. Both diastereomers would thus pass through the same radical intermediate, which can be used to explain the E -selectivity.
Even though the carbanion is not configurationally or conformationally stable, it will prefer an arrangement with the R-groups further apart that will later lead to the E -alkene: Keck demonstrated in that when the sodium amalgam reaction is run in MeOD as solvent, deuterium is incorporated into the product, in contrast to the absence of incorporation seen in the SmI2 reduction.
Keck, K. Savin, M. Weglarz, J. The classical Julia Olefination with sodium amalgam might possibly proceed via an initial elimination to an alkenyl sulfone, which would then undergo homolytic cleavage involving single electron transfer.
Since the cis- and trans-vinyl radicals can equilibrate at this stage and the trans-radical is the more stable of the two, both diastereomeric acetoxy sulfones would still lead selectively to the same product. A disadvantage of the Julia Olefination is its low tolerance for reducible functional groups.
The E -selectivity is generally good to very good for alkenes with a low degree of substitution, while the selectivity improves as a function of increased branching in the substitutents. Pospisil, T. Pospisil, I. Marko, Org. Site Search.
Kocienski explored the scope and limitation of the reaction, and today this olefination is formally known as the Julia-Lythgoe olefination. In the initial versions of the reactions, the elimination was done under reductive conditions. More recently, a modified version that avoids this step was developed. The former version is sometimes referred to as the Julia-Lythgoe olefination, whereas the latter is called the Julia-Kocienski olefination. In the reductive variant, the adduct is usually acylated and then treated with a reducing agent, such as sodium amalgam   or SmI2. The phenyl sulfone anion 2 reacts with an aldehyde to form the alkoxide 3.