A homologous series of O- and N-functionalized 2,2-difluoro-1,3-benzodioxoles: An exercise in organometallic methodology
The conversion of 2,2-difluoro-1,3-benzodioxole, an exceptionally acidic arene, via a 4-lithiated intermediate into more than three dozen new derivs. 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, di-Me sulfate), C2-electrophiles (oxalic acid diesters, oxirane), C3-electrophiles (oxetane), and higher alkyl iodides. The resulting carboxylic acid 2,2-difluoro-1,3-benzodioxole-4-carboxylic acid may be treated with organolithium compds. to afford ketones and the aldehyde 2,2-difluoro-1,3-benzodioxole-4-carboxaldehyde may be condensed with nitromethane or acetic anhydride under basic conditions. If not oxidized with chromium trioxide to the corresponding carboxylic acids, the alcs., e.g., 4-(3-hydroxypropyl)-2,2-difluoro-1,3-benzodioxole can be transformed into the corresponding bromides or sulfonates. Their condensation with nitrogen-contg. C0-nucleophiles (hydroxylamine, sodium azide, potassium phthalimide), C1-nucleophiles (potassium cyanide), and C2-nucleophiles (acetonitrile) opens a convenient access to amines. Other reactions gave, despite a proven track record in other areas, only moderate yields. [on SciFinder (R)]
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Schlosser, M., Gorecka, J., & Castagnetti, E. (2003). A homologous series of O- and N-functionalized 2,2-difluoro-1,3-benzodioxoles: An exercise in organometallic methodology. European Journal of Organic Chemistry, (3), 452–462. https://doi.org/10.1002/ejoc.200390079
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WOS:000180805100007
2003
3
452
462
CAN 138:401634 28-5 Heterocyclic Compounds (More Than One Hetero Atom) Institute of Chemistry and Molecular Sciences, BCh,Ecole Polytechnique Federale,Lausanne,Switz. Journal 1434-193X written in English. 68-12-2; 75-21-8 (Oxirane); 79-10-7 (Acrylic acid); 95-92-1 (Diethyl oxalate); 98-09-9 (Benzenesulfonyl chloride); 107-30-2 (Chloromethyl methyl ether); 503-30-0 (Oxetane); 941-55-9; 1074-82-4 (Potassium phthalimide); 1583-59-1 (2,2-Difluoro-1,3-benzodioxole); 1663-39-4 (tert-Butyl acrylate); 3210-08-0 (4-Iodo-1-butanol) Role: RCT (Reactant), RACT (Reactant or reagent) (prepn. of functionalized 2,2-difluoro-1,3-benzodioxoles by reactions of 4-lithiated intermediate with carbon electrophiles and nitrogen nucleophiles); 72769-03-0P; 72769-05-2P; 106876-53-3P; 119895-68-0P; 126120-83-0P; 126120-85-2P (2,2-Difluoro-1,3-benzodioxole-4-carboxylic acid); 127333-93-1P; 144584-66-7P; 154257-65-5P; 157437-24-6P; 161886-18-6P; 334778-39-1P; 531508-34-6P; 531508-36-8P; 531508-37-9P; 531508-38-0P; 531508-40-4P; 531508-41-5P; 531508-42-6P; 531508-43-7P; 531508-50-6P; 531508-51-7P; 531508-52-8P; 531508-53-9P; 531508-54-0P; 531508-55-1P; 531508-56-2P; 531508-57-3P; 531508-58-4P; 531508-59-5P; 531508-60-8P; 531508-61-9P Role: RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (prepn. of functionalized 2,2-difluoro-1,3-benzodioxoles by reactions of 4-lithiated intermediate with carbon electrophiles and nitrogen nucleophiles); 106876-54-4P; 126120-86-3P; 157437-25-7P; 531508-32-4P; 531508-33-5P; 531508-35-7P; 531508-39-1P; 531508-44-8P; 531508-45-9P; 531508-46-0P; 531508-47-1P; 531508-48-2P; 531508-49-3P; 531508-62-0P Role: SPN (Synthetic preparation), PREP (Preparation) (prepn. of functionalized 2,2-difluoro-1,3-benzodioxoles by reactions of 4-lithiated intermediate with carbon electrophiles and nitrogen nucleophiles)
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