Julia-Lythgoe Olefination

• General Characteristics

The Julia-Lythgoe olefination involves the nucleophilic addition of lithiosulfones to carbonyl compounds, acylation, and reductive treatment of the resulting β-acyloxysulfones. E-Alkenes are formed selectively regardless of the stereochemistry of the β-acyloxysulfones. Sodium amalgam or samarium diiodide is generally used for the reduction.

Lithiosulfones are relatively reactive and tend to react effectively with the substrates less reactive under other olefination conditions. It can be used to synthesize tetrasubstituted olefins but controlling the geometry is difficult.

The tuning of the aryl ring of the sulfone led to the development of the modified one-pot Julia olefination, which does not require reduction by sodium amalgam. However, this modification somewhat compromise the E/Z selectivity.

More recently, the conditions utilizing PT (phenyltetrazole)-sulfone group was reported in 1998 by Kocienski (the Julia-Kocienski olefination). This modified procedure provides high E-selectivity.

• General References

・Julia, M.; Paris, J. M. Tetrahedron Lett. 1973, 4833. doi:10.1016/S0040-4039(01)87348-2
・Kocienski, P. J.; Lythgoe, B. J. Chem. Soc. Perkin Trans, 1 1980, 1045. DOI: 10.1039/P19800001045
・Keck, G. E.; Savin, K. A.; Weglarz, M. A. J. Org. Chem. 1995, 60, 3194. doi:10.1021/jo00115a041
・Modified Julia: Baudin, J. B.; Hareau, G.; Julia, S. A.; Ruel, O. Tetrahedron Lett. 1991, 32, 1175. doi:10.1016/S0040-4039(00)92037-9
・Julia-Kocienski Modification: Blakemore, P, R.; Cole, W. J.; Kocienski, P. J.; Morley, A. Synlett 1998, 26. doi:10.1055/s-1998-1570
・Review: Kocienski, P. J. Phosphorus and Sulfur 1985, 24, 97.
・Review: Kelly, S. E. Compreheisive Organic Synthesis 1991, 1, 792.
・Review of Julia-Kocienski Reaction: Blakemore, P. R. JCS Perkin Trans. 1 2002, 2563. doi: 10.1039/b208078h

• Reaction Mechanism

The mechanism is not fully understood but the high E-selectivity is considered to result from the thermodynamically controlled isomerization of the radical or anionic intermediate formed in the SET reduction step. The reaction using samarium diiodide is known to take a different path. (Ref. J. Org. Chem. 1995, 60, 3194.)

• Examples

The synthesis of bryostatin 2^[1]: The Julia olefination is frequently used in the synthesis of long chain and macrolide compounds.

The synthesis of ent-lepadin F.^[2]

• Experimental Procedure

A typical example of the Julia-Kocienski olefination.^[2]

• Experimental Tips

• References

[1] Evans, D. A. et al. J. Am. Chem. Soc. 1999, 121, 7540. DOI: 10.1021/ja990860j
[2] Blakemore, P, R.; Cole, W. J.; Kocienski, P. J.; Morley, A. Synlett 1998, 26. doi:10.1055/s-1998-1570

• Related Books

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arylsulfones, E-selective olefination of aldehydes, synthesis of alkenes