Lithium 2-Lithiophenoxide

[55274-02-7]  · C6H4Li2O  · Lithium 2-Lithiophenoxide  · (MW 105.98)

reacts with electrophiles to give substituted phenols

Solubility: sol ethereal solvents.

Preparative Methods: conveniently prepared and used in situ by one of two methods. The first reported preparation1 involves the treatment of o-bromophenol with n-Butyllithium at 25 °C to generate the dilithio species (eq 1). A subsequent report2 described an alternative preparation by directed ortho deprotonation of phenol with t-Butyllithium (eq 2).

Handling, Storage, and Precautions: moisture sensitive; freshly prepare before use. Long term stability has not been determined. Reactions should be run under an inert atmosphere.

Reactions.

The reagent prepared by either route has been shown to react with electrophiles at the ortho carbon (eqs 3 and 4).3 The electrophiles studied included hindered ketones and enolizable aldehydes and ketones.

The corresponding meta4 and para isomers are prepared by the halogen-metal exchange route with t-BuLi. The dilithio species (both meta and para isomers) react with a variety of electrophiles including aldehydes, ketones (eq 5), and amides.

Related Reagents.

The corresponding sulfur analogs are prepared similarly to the phenolic examples.5 Treatment of thiophenol with n-BuLi at room temperature in the presence of N,N,N,N-Tetramethylethylenediamine gives rise to the lithium 2-lithiothiophenoxide in solution which can be trapped with electrophiles (eq 6).

The meta and para isomers are prepared by the halogen-metal exchange route and have been shown to react with acylating reagents (eq 7).4

Similar reagents in which the phenolic oxygen is protected (methyl or silyl ether) prior to lithiation have been reported.6 An example in the synthesis of thromboxane A2 antagonists is shown (eq 8). See also o-Lithioanisole.

It is also possible to generate related C,O,O-trilithiated species by the halogen-metal exchange strategy (eq 9).7 Higher temperatures and sonication appear to be necessary for trianion formation.


1. (a) Gilman, H.; Arntzen, C. E.; Webb, F. J. JOC 1945, 10, 374. (b) Gilman, H. OR 1951, 6, 339.
2. Posner, G. H.; Canella, K. A. JACS 1985, 107, 2571.
3. (a) Talley, J. J.; Evans, I. A. JOC 1984, 49, 5267. (b) Talley, J. J. JOC 1985, 50, 1695. (c) Heinicke, J.; Tzschach, A. JPR 1983, 325, 232.
4. Selnick, H. G.; Bourgeois, M. L.; Butcher, J. W.; Radzilowski, E. M. TL 1993, 34, 2043.
5. (a) Masson, S.; Saint-Clair, J.; Saquet, M. S 1993, 485. (b) Block, E.; Ofori-Okai, G.; Zubieta, J. JACS 1989, 111, 2327. (c) Figuly, G. D.; Loop, C. K.; Martin, J. C. JACS 1989, 111, 654. (d) Smith, K.; Lindsay, C. M.; Pritchard, G. J. JACS 1989, 111, 665.
6. Misra, R. N.; Brown, B. R.; Han, W-C.; Harris, D. N.; Hedberg, A.; Webb, M. L.; Hall, S. E. JMC 1991, 34, 2882.
7. Saá, J. M.; Morey, J.; Suñer, G.; Frontera, A.; Costa, A. TL 1991, 32, 7313.

Harold G. Selnick

Merck Research Laboratories, West Point, PA, USA



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