Those of you in the pharma industry will be familiar with the acronym NDA standing for New Drug Application, but there could be a new chemical use for NDA as the sodium equivalent of LDA (lithium diisopropylamide), although the authors use NaDA, so perhaps we should use LiDA instead of LDA. In this paper David Collum and co-workers describe the preparation of NaDA from sodium dispersion in toluene and diisopropylamine. The key to this paper is the use of amine solvents such as N,N-dimethylethylamine and related trialkylamines to study the reactivity of NaDA. NaDA shows excellent solubility in these solvents and concentrated stock solutions are stable for months with refrigeration.
Reactions studied include metalation of arenes, epoxides, ketones, hydrazones, dienes, as well as alkyl and vinyl halides. Metalations are generally very rapid and in many cases far more rapid than the equivalent reaction with LDA. The sodiated products are generally show good solubility, but of course the big advantage is that sodium is orders of magnitude cheaper than lithium.
Y. Ma, R.F. Algera, and D.B. Collum,* J. Org. Chem., 2016, 81, 11312-11315.
