Lithium technology - an alternative to alkyllithiums

15 September 2004

There are not many commercially available alkyl lithium reagents (although those that are available come in many different grades /concentrations/solutions) and those that are available may not be the best for your particular reaction. At a recent conference in Berlin, Bernhardt Rausch of Clariant described their lithium technology alternative to using alkyl lithiums such as butyllithium or hexyllithium. The basis of the technology is to use lithium metal and form the optimal lithium reagent in situ. So for example 4-formylbenzeneboronic acid (4-formylphenylboronic acid) can be prepared from an acetal of 4 chlorobenzaldehyde by direct lithiation with lithium metal followed by quenching with a borate ester such as trimethyl borate or triisopropyl borate followed by acidic work-up (see Scheme 1).

Ortholithiations can be carried out by adding lithium metal to an alkyl halide in the presence of the substrate followed by the appropriate Electrophile, as shown in Scheme 2. Using this approach the lithium reagent can be tailored and fine-tuned to give improved yields and / or selectivities.

B. Rausch, presentation at Modern Synthetic Methods — Reaction to Reality, Berlin, May 6-7, 2004