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A Homologous Series of O ‐ and N ‐Functionalized 2,2‐Difluoro1,3‐benzodioxoles: an Exercise in Organometallic Methodology
Author(s) -
Schlosser Manfred,
Gorecka Joanna,
Castagnetti Eva
Publication year - 2003
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.200390079
Subject(s) - chemistry , electrophile , nucleophile , chromium trioxide , medicinal chemistry , organic chemistry , dimethylformamide , oxetane , aldehyde , acetic anhydride , formylation , acetic acid , azide , chromium , catalysis , solvent
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 C 0 ‐electrophiles (4‐toluenesulfonyl azide, fluorodimethoxyborane, iodine), C 1 ‐electrophiles (carbon dioxide, N , N ‐dimethylformamide, formaldehyde, dimethyl sulfate), C 2 ‐electrophiles (oxalic acid diesters, oxirane), C 3 ‐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 C 0 ‐nucleophiles (hydroxylamine, sodium azide, potassium phthalimide), C 1 ‐nucleophiles (potassium cyanide), and C 2 ‐nucleophiles (acetonitrile) opens a convenient access to the amines 3 . Other reactions gave, despite a proven track record in other areas, only moderate yields. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)