Dianions, chemoselective reactions

The process is assumed to take place by a chemoselective attack of the dianion 2-223 at the bromomethyl group of 2-221 and subsequent nucleophilic attack of the resultant monoanion 2-224 onto the epoxide moiety to give 2-225. Use of the sodium-lithium-salt 2-223 of the dicarbonyl compound 2-220, the reaction temperature as well as the Lewis acid LiC104, are crucial. The reaction seems to be quite general, since various 1,3-dicarbonyl compounds can be converted into the corresponding furans. 

The converse of this idea is central to a useful bit of chemoselectivity that can be obtained in the reactions of dianions. 1-Propynol can be deprotonated twice by strong bases—first, at the hydroxyl group to make an alkoxide anion (the pIQ of the OH group is about 16) and, secondly, at the alkyne (pKa of the order of 25) to make a reacts with electrophiles it always reacts at the alkynyl anion and not at the alkoxide. 

Chemoselective (V-ethylation of Boc-amino acids can be accomplished without racemization via the corresponding dianions. Thus, (V-t-butoxycarbonylamino acid (35) was converted into dianion (36) by treatment with 2 equiv. of Bu Li, followed by the reaction with 1 equiv. of triethyloxonium tetrafluoro-borate to give (V-ethyl derivative (37) along with a trace of ethyl ester (38). On treatment with 2.2 equiv. of the triethyloxonium salt (36 R = Ph) gave (38 R = Ph) in 95% yield (Scheme 17). ... 

The indole-based drug 129 is clearly made by acylating an indole 127 and this was the last step in the synthesis, The problem here is chemoselectivity. The answer is the usual one of last in, first out . The anion of the indole will be needed to ensure reaction at nitrogen but the anion of the tetrazole will be formed first. Two molecules of NaH make the dianion 128 and the less stable anion, that of the indole, reacts first.14... 

Uchiyama, M., Fumyama, T, Kobayashi, M., Matsumoto, Y. and Tanaka, K. Toward a Protecting-Group-Free Halogen-Metal Exchange Reaction Practical, Chemoselective Metalation of Functionalized Aromatic Hahdes Using Dianion-type Zincate, Bu,Zn-Lij. JAm Chem Soc 128, 8404-8405 (2006). 

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