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.
|Country:||Papua New Guinea|
|Published (Last):||9 April 2007|
|PDF File Size:||13.3 Mb|
|ePub File Size:||18.30 Mb|
|Price:||Free* [*Free Regsitration Required]|
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.
Other hetero cyclic substituents can assume these roles, and offer somewhat different selectivity: Specifically, the pyridinyl sulfone exhibits high Z-selectivity, while the 1-phenyl-1H-tetrazolyl sulfone PT-SO2R gives somewhat better E-selectivity than the BT sulfones. The reason for this is the sterically demanding phenyl group, which favors the following transition state: The 1-phenyl-1H-tetrazolyl sulfones do not have a tendency to self-condense, so they can first be deprotonated with base and then reacted with the aldehyde.
This makes possible a far milder reaction process, including reactions with base-sensitive aldehydes. The following table shows the selectivity and yields for BT and PT sulfones in various solvents, where they are first metalated with various bases and then reacted with an aldehyde. Blakemore, W. Cole, P. Kocienski, A. Morley, Synlett, , In contrast to the classical Julia Olefination, the Modified Julia Olefination offers the possibility of saving one or two synthesis steps.
In addition, there are fewer problems with scale-up than with the classical variant. Ando, T. Kobayashi, N. Uchida, Org. Alonso, C. Najera, M. Varea, Tetrahedron Lett. Pospisil, I. Marko, Org. Blakemore, D.
Ho, W. Nap, Org. Billard, R. Robiette, J. Lebrun, P. Le Marquand, C. Berthelette, J. Gueyrard, R. Haddoub, A. Salem, N. Bacar, P. Goekjian, Synlett, , 17, Simlandy, S. Mukherjee, J. Application to the Synthesis of Maculalactone B N.
Dussart, H. Trinh, D. Gueyrard, 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.