Tribromomethyllithium

LiCBr3

[16644-71-6]  · CBr3Li  · Tribromomethyllithium  · (MW 258.65)

(nucleophilic tribromomethylation1)

Physical Data: low temperature 13C and 6Li NMR data are available,2 as are matrix IR data.3

Preparative Methods: solutions of the title compound can be obtained by treatment of Carbon Tetrabromide with n-Butyllithium or Phenyllithium in THF/ether/hexane (4:4:1) at -110 °C for ca. 1 hour,4 by deprotonation of Bromoform with Dichloromethyllithium in THF at -100 °C,5 and by deprotonation of CHBr3 with lithium dimethylamide in THF/HMPA at -105 °C.6

Handling, Storage, and Precautions: there is considerable decomposition of the reagent at -100 °C over several hours,4 increasing in rate with increasing temperature. Comparison of ether and THF as solvents for reagents of this type suggests that the latter both accelerates the formation of a-halo organolithiums at low temperature and increases their thermal stability.7

General Considerations.

Alkyllithiums bearing halogens on the a-carbon are frequently referred to as carbenoids reflecting a major mode of reactivity. Good general reviews of such species are available.1 At very low temperatures, however, this reagent reacts like a typical alkyllithium. It should be noted that LiCBr3 has been studied much less than the analogous Trichloromethyllithium, perhaps due to the greater thermal stability of the latter. However, the reagents are not analogous in all of their reactions.

Nucleophilic Tribromomethylation/Carbonyl Homologation.

The reagent can be used in the displacement of iodides and bromides to produce terminal tribromoalkanes (1) (eq 1).8 Such compounds serve as intermediates in a homologation process.9 The tribromoalkane can be metalated to (2) and added to an aldehyde to provide an intermediate lithioalkoxide (eq 2). This can be treated with n-BuLi to provide the dilithium reagent (3), which undergoes Fritsch-Buttenberg-Wiechell rearrangement to either (4) or (5) depending on the identity of RŽ. Quenching of the mixture gives rise to (6) and/or (7) in 50-100% yield. The aldehyde is usually formed as a minor product when benzaldehydes or alkenals are used as substrates. Cyclic ketones undergo ring expansion in the same process as shown in eq 3.

The adducts of LiCBr3 with cyclohexanone and other ketones have been prepared by Yamamoto in a general synthesis of polyhalomethylcarbinols.10 Addition of Lithium Dicyclohexylamide to a solution of cyclohexanone and CHBr3 in THF results in deprotonation of the CHBr3 and carbonyl addition giving the adduct (eq 4).

Dibromomethylenation.

The reagent can also be used to convert aldehydes to 1,1-dibromoalkenes.11 Addition of LiCBr3 to aldehydes and O-alkylation with Iodomethane, Chlorotrimethylsilane, or Acetyl Chloride gives the alkoxy (or acyloxy) tribromoalkane (8) (eq 5). Treatment of (8) with slightly more than 1 equiv of n-BuLi in THF/ether at -60 °C results in formation of the dibromoalkene (10) by loss of ROLi from the presumed intermediate (9). Yields are moderate.

Cyclopropanation/C-H Insertion.

Cory has developed a clever in situ procedure for the construction of bridged ring systems incorporating a cyclopropane.12 Treatment of CBr4 with Methyllithium at -75 °C followed by an alkene results in the formation of a dibromocyclopropane via decomposition of LiCBr3 to dibromocarbene. Treatment with a second equivalent of MeLi transmetalates a halogen and promotes carbene formation via a-elimination of LiBr. The carbene can insert into a proximate C-H bond, resulting in a large increase in molecular complexity in a single operation. Thus (11) is converted to (12) and (13) in good yield (eq 6), while the more complex (14) is converted to (15) in 26% yield (eq 7).

Counterions Other than Li.

The analogous reagents NaCBr3 and KCBr3 have also been prepared by deprotonation of CHBr3 using the requisite metal hexamethyldisilazide.13 No significant chemical reactivity was reported.

Related Reagents.

Dibromomethyllithium; Dichloromethyllithium; Trichloromethyllithium.


1. (a) Siegel, H. Top. Curr. Chem. 1982, 106, 55. (b) Taylor, K. G. T 1982, 38, 2751. (c) Kobrich, G. AG(E) 1972, 11, 473. (d) Kobrich, G. AG(E) 1967, 6, 41.
2. (a) Seebach, D.; Siegel, H.; Gabriel, J.; Hassig, R. HCA 1980, 63, 2046. (b) Heinzer, J.; Oth, J. F. M.; Seebach, D. HCA 1985, 68, 1848. (c) Seebach, D.; Hassig, R.; Gabriel, J. HCA 1983, 66, 308. (d) Siegel, H.; Hiltbrunner, K.; Seebach, D. AG(E) 1979, 18, 785.
3. Andrews, L.; Carver, T. G. J. Phys. Chem. 1968, 72, 1743.
4. Kobrich, G.; Fischer, R. H. CB 1968, 101, 3230.
5. Kobrich, G.; Fischer, R. H. CB 1968, 101, 3208.
6. Castro, B.; Villieras, J. CR(C) 1967, 264, 1609.
7. (a) Kobrich, G.; Merkle, H. R.; Trapp, H. TL 1965, 969. (b) Kobrich, G.; Merkle, H. R. CB 1966, 99, 1782. (c) Kobrich, G.; Trapp, H. CB 1966, 99, 670. (d) Kobrich, G.; Breckoff, W. E.; Heinemann, H.; Akhtar, A. JOM 1965, 3, 492.
8. Villieras, J.; Bacquet, C.; Normant, J. F. BSF(2) 1975, 1797.
9. Villieras, J.; Perriot, P.; Normant, J. F. S 1979, 968.
10. (a) Taguchi, H.; Yamamoto, H.; Nozaki, H. JACS 1974, 96, 3010. (b) Taguchi, H.; Yamamoto, H.; Nozaki, H. BCJ 1977, 50, 1588.
11. Perriot, P.; Normant, J. F.; Villieras, J. CR(C) 1979, 289, 259.
12. Cory, R. M.; Burton, L. P. J.; Pecherle, R. G. SC 1979, 9, 735.
13. Martel, B.; Hiriart, J. M. TL 1971, 2737.

Kim F. Albizati

University of California, San Diego, La Jolla, CA, USA



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