Extensive Functionalization of Aryllithiums
(Rated as: excellent)
A Homologous Series of O- and N-Functionalized 2,2-Difluoro-1,3-benzodioxoles: an Exercise in Organometallic Methodology
Eur. J. Org. Chem. 2003, 452-462
The conversion of 2,2-difluoro-1,3-benzodioxole, an exceptionally acidic arene, via a 4-lithiated intermediate into more than three dozen new derivatives was conceived as a case study. The lithiated species was trapped by C0-electrophiles (4-toluenesulfonyl azide, fluorodimethoxyborane, iodine), C1-electrophiles (carbon dioxide, N,N-dimethylformamide, formaldehyde, dimethyl sulfate), C2-electrophiles (oxalic acid diesters, oxirane), C3-electrophiles (oxetane), and higher alkyl iodides. The resulting carboxylic acid 1a may be treated with organolithium compounds to afford ketones (e.g. 10) and the aldehyde 9 can be condensed with nitromethane or acetic anhydride under basic conditions. If not oxidized with chromium trioxide to the corresponding carboxylic acids, the alcohols 2b, 2c, and 2d can be transformed into the corresponding bromides (12) or sulfonates (13). Their condensation with nitrogen-containing C0-nucleophiles (hydroxylamine, sodium azide, potassium phthalimide), C1-nucleophiles (potassium cyanide), and C2-nucleophiles (acetonitrile) opens a convenient access to the amines 3.