Bromomethyllithium1

BrCH2Li

[92533-92-1]  · CH2BrLi  · Bromomethyllithium  · (MW 100.87)

(converts aldehydes or ketones to oxiranes;1 B(OR)3 to BrCH2B(OR)2;1 R1B(OR2)2 to R1CH2B(OR2)21)

Physical Data: stable at -110 °C in the presence of LiBr; unstable at higher temperatures; unstable even at -130 °C in the absence of LiBr.4,5

Preparative Methods: preferably by addition of MeLi/LiBr or n-BuLi solution dropwise to a vigorously stirred solution of CH2Br2 and the substrate in THF cooled with a dry ice-acetone bath.1

Handling, Storage, and Precautions: see n-Butyllithium and Dibromomethane. The reagent must be generated under an inert atmosphere of nitrogen or argon.

Oxirane Formation.

Aldehydes and ketones are efficiently converted to oxiranes by BrCH2Li generated by addition of BuLi to CH2Br2 in the presence of the carbonyl compound in THF cooled with a -78 °C bath (internal temperature below -65 °C), followed by standing at rt for 15 h (eq 1).1

With BrCH2Li the yields were uniformly high in all four examples illustrated (eqs 2-5). The first three transformations had been carried out previously with Chloromethyllithium, with reported yields of 91-99%2 and replicated yields of 88-93%.1 However, with the last example, ethyl levulinate, ClCH2Li yielded only 40% oxirane and BrCH2Li yielded 93%. Thus BrCH2Li appears to be the more selective reagent, at least with regard to interfering ester functionality.

The first reported generation of BrCH2Li from CH2Br2 and BuLi in the presence of a ketone yielded only 20% of the corresponding oxirane.3 Present knowledge implies that there was an error in experimental procedure, possibly mere failure to allow enough time for oxirane ring closure. The use of Li dispersion with CH2Br2 yielded 35-52% of oxiranes in eight examples, 95% in one,3 and is clearly not a practical method.

It is also possible to preform the BrCH2Li in the presence of LiBr in THF-Et2O-pentane at -115 °C.4 The reagent is unstable in the absence of LiBr or above -110 °C.4,5 Although the preformed reagent gives satisfactory yields of oxiranes, this method is obsolete for any known practical purpose.

Boronic Esters.

Dropwise addition of BuLi to a mixture of CH2Br2 and Triisopropyl Borate in THF stirred below -65 °C (-78 °C bath) results in the formation of an addition compound of BrCH2Li with the borate, which is converted by anhydrous acid to diisopropyl (bromomethyl)boronate (eq 6).1 This preparation is easily scaled up to 2-mol batches.

With simple boronic esters, BrCH2Li adds to the boron atom to form a borate complex, which on warming to rt rearranges to form the homologous boronic ester (eqs 7 and 8).1 Unexpectedly, the presence of oxygen functionality has a severely adverse effect on boronic ester homologation with BrCH2Li (eq 9).1 This result contrasts with the previous finding with ClCH2Li, which accomplished the conversion of eq 9 in 90% yield.2

Homologs of Bromomethyllithium.

Although the first attempt to use BuLi to generate BrCH2Li from CH2Br2 in the presence of a ketone gave an anomalous poor result,3 similar treatment of MeCHBr2, Me2CBr2, PhCHBr2, or EtOCHBr2 readily yielded the corresponding oxiranes.6 Typical examples are illustrated (eqs 10 and 11). It should be noted that where both the carbonyl compound and the halide are unsymmetrical, diastereomeric mixtures result.

Several examples of RCHBrLi have also been preformed at -115 °C and reacted with carbonyl compounds to form oxiranes or bromohydrins.4,7

Related Reagents.

Chloromethyllithium; Dibromomethyllithium; Dichloromethyllithium; Dimethylsulfonium Methylide; Tribromomethyllithium; Trichloromethyllithium.


1. Michnick, T. J.; Matteson, D. S. SL 1991, 631.
2. Sadhu, K. M.; Matteson, D. S. OM 1985, 4, 1687.
3. Cainelli, G.; Umani Ronchi, A.; Bertini, F.; Grasselli, P.; Zubiani, G. T 1971, 27, 6109.
4. Tarhouni, R.; Kirschleger, B.; Rambaud, M.; Villieras, J. TL 1984, 25, 835.
5. Villieras, J.; Rambaud, M.; Kirschleger, B.; Tarhouni, R. BSF 1985, 837.
6. Cainelli, G.; Tangari, N.; Umani Ronchi, A. T 1972, 28, 3009.
7. (a) Villieras, J.; Tarhouni, R.; Kirschleger, B.; Rambaud, M. BSF 1985, 825. (b) Villieras, J.; Kirschleger, B.; Tarhouni, R.; Rambaud, M. BSF 1986, 470.

Donald S. Matteson

Washington State University, Pullman, WA, USA



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