Julia-Kocienski Olefination

04 November, 2015 / by SK / in Reactions

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General Characteristics

The original Julia olefination procedure was somewhat inconvenient as it required three operations (nucleophilic addition, acetylation, and elimination using toxic Na amalgam).

A modified single-step method was developed later by fine-tuning the aromatic sulfone moiety, although the control of E/Z selectivity remained unsolved. Kocienski developed a further improved version using PT(phenyltetrazole)-sulfone (the Julia-Kocienski olefination). This reaction gives olefin products with high E-selectivity.

General References

Baudin, J. B.; Hareau, G.; Julia, S. A.; Ruel, O. Tetrahedron Lett. 1991, 32, 1175. doi:10.1016/S0040-4039(00)92037-9
Blakemore, P. R.; Cole, W. J.; Kocienski, P. J.; Morley, A. Synlett 1998, 26. doi:10.1055/s-1998-1570
Kocienski, P. J.; Bell, A.; Blakemore, P. R. Synlett 2000, 365. DOI: 10.1055/s-2000-6536

Blakemore, P. R. JCS Perkin Trans. 1 2002, 2563. doi: 10.1039/b208078h
Aissa, C. Eur. J. Org. Chem. 2009, 1831. DOI: 10.1002/ejoc.200801117
Zajc, B.; Kumar, R. Synthesis 2010, 1822. DOI: 10.1055/s-0029-1218789
Chatterjee, B.; Bera, S.; Mondal, D. Tetrahedron: Asymmetry 2014, 25, 1. doi:10.1016/j.tetasy.2013.09.027
Pfund, R.; Lequeux, T.; Gueyrard, D. Synthesis 2015, 47, 1534. DOI: 10.1055/s-0034-1380548

Reaction Mechanism

The mechanism involves intramolecular attack of the alkoxide intermediate to the tetrazole ring and elimination (the Smiles rearrangement).

Examples

An application to the synthesis of ent-lepadin F.

The modified sulfone reagent provides a practical way to methylenate carbonyl compounds.^[1]

The synthesis of (+)-ambruticin.^[2]

The synthesis of fluorinated alkenes.^[3]

Experimental Procedure

A typical experimental procedure for the Julia-Kocienski olefination.^[4]

To a stirred solution of the PT-sulfone (2.80 g, 10.0 mmol) in anhydrous DME (40 mL) under nitrogen at -55°C was added dropwise via cannula a solution of potassium hexamethyldisilazide (2.74 g, 80% by weight, 11.0 mmol) in DME (20 mL) over 10 min. The yellow-orange solution was stirred for 70 min during which time the solution became dark brown. Neat cyclohexanecarboxaldehyde (1.67 g, 15.0 mmol) was added dropwise over 5 min. and the mixture stirred at -55°C for 1h during which time the colour changed to light yellow. The cooling bath was removed and the mixture stirred at ambient temperature overnight whereupon H₂O (5 mL) was added and stirring continued for 1 h. The mixture was diluted with Et₂O (150 mL) and then washed with H₂O (200 mL). The aqueous phase was extracted with Et₂O (3 x 30 mL) and the combined organic layeres washed with H₂O (3 x 50 mL) and brine (50 mL). After drying over MgSO₄, the solvent was removed in vacuo to yield a pale yellow oil (2.74 g) which was purified by column chromatography (SiO₂, hexanes) to give the desired alkene (1.18 g, 7.1 mmol, 71%) as a colourless oil after kugelrohr distillation (bp 180°C/15 mmHg).

Experimental Tips

References

(a) Ando, K.; Kobayashi, T.; Uchida, N. Org. Lett. 2015, 17, 2554. DOI: 10.1021/acs.orglett.5b01049 (b) Aissa, C. J. Org. Chem. 2006, 71, 360. DOI: 10.1021/jo051693a
Liu, P.; Jacobsen, E. N. J. Am. Chem. Soc. 2001, 123, 10772. DOI: 10.1021/ja016893s
Zhao, Y.; Huang, W.; Zhu, L.; Hu, J. Org. Lett. 2010, 12, 1444.　DOI: 10.1021/ol100090r
Blakemore, P, R.; Cole, W. J.; Kocienski, P. J.; Morley, A. Synlett 1998, 26. doi:10.1055/s-1998-1570