Trifluoromethoxy-substituted anilines undergo hydrogen/lithium permutation (\"metalation\") with optional site selectivity depending on the N-protective group employed. N-tert-Butoxycarbonyl-2- and -4-(trifluoromethoxy)aniline react with tert-BuLi at the nitrogen-adjacent 6- and 2-position affording, after electrophilic trapping, the corresponding substituted anilines I (R1 = F3CO, R2 = H, R3 = HO2C; R1 = H, R2 = F3CO, R3 = Me, CHO, HO2C, HOCH2CH2). In contrast, deprotonation of the N,N-bis(trimethylsilyl)-substituted 4-(trifluoromethoxy)aniline occurs at the oxygen-neighboring 3-position. Sec-BuLi attacks 3-trifluoromethoxy-N-(trimethylsilyl)aniline at the 2-position, but 3-trifluoromethoxy-N,N-bis(trimethylsilyl)aniline at the 4-position to provide the corresponding acids II (R4 = HO2C, R5 = H; R4 = H, R5 = HO2C), resp., after carboxylation. The synthesis of two new benzodiazepines III (R6 = F3CO, R7 = H, R8 = F; R6 = Cl, R7 = HO, R8 = F3CO) illustrates the preparative potential of the aniline functionalization mediated by organometallic reagents. [on SciFinder (R)]
Title
Trifluoromethoxy Substituted Anilines: Metalation as the Key Step for Structural Elaboration
Published in
Journal of Organic Chemistry
Volume
68
Issue
12
Pages
4693-4699
Date
2003
Note
CAN 139:117169 25-4 Benzene, Its Derivatives, and Condensed Benzenoid Compounds Institut de Chimie moleculaire et biologique,Ecole Polytechnique Federale,Lausanne,Switz. Journal 0022-3263 written in English. 403646-45-7P Role: RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (amidation; prepn. of functionalized anilines, aminobenzoic acids and benzodiazepinones via regioselective metalation/electrophilic substitution of trifluoromethoxy-substituted anilines); 561304-53-8P Role: RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (azidation; prepn. of functionalized anilines, aminobenzoic acids and benzodiazepinones via regioselective metalation/electrophilic substitution of trifluoromethoxy-substituted anilines); 94651-33-9 (2-(Trifluoromethoxy)benzaldehyde) Role: RCT (Reactant), RACT (Reactant or reagent) (electrophile; prepn. of functionalized anilines, aminobenzoic acids and benzodiazepinones via regioselective metalation/electrophilic substitution of anilines); 446-52-6 (2-Fluorobenzaldehyde) Role: RCT (Reactant), RACT (Reactant or reagent) (electrophile; prepn. of functionalized anilines, aminobenzoic acids and benzodiazepinones via regioselective metalation/electrophilic substitution of trifluoromethoxy-substituted anilines); 561304-52-7P Role: RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (intramol. heterocyclization; prepn. of functionalized anilines, aminobenzoic acids and benzodiazepinones via regioselective metalation/electrophilic substitution of trifluoromethoxy-substituted anilines); 18437-66-6 Role: RCT (Reactant), RACT (Reactant or reagent) (prepn. of functionalized anilines, aminobenzoic acids and benzodiazepinones via regioselective metalation/electrophilic substitution of anilines); 561304-62-9P; 561304-63-0P; 561304-64-1P; 561304-65-2P; 561304-66-3P Role: RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (prepn. of functionalized anilines, aminobenzoic acids and benzodiazepinones via regioselective metalation/electrophilic substitution of anilines); 561304-67-4P Role: SPN (Synthetic preparation), PREP (Preparation) (prepn. of functionalized anilines, aminobenzoic acids and benzodiazepinones via regioselective metalation/electrophilic substitution of anilines); 124-68-5 (2-Amino-2-methyl-1-propanol); 461-82-5 (4-(Trifluoromethoxy)aniline); 1535-73-5 (3-(Trifluoromethoxyaniline); 1535-75-7 (2-(Trifluoromethoxy)aniline) Role: RCT (Reactant), RACT (Reactant or reagent) (prepn. of functionalized anilines, aminobenzoic acids and benzodiazepinones via regioselective metalation/electrophilic substitution of trifluoromethoxy-substituted anilines); 212696-37-2P; 220107-35-7P; 561304-39-0P; 561304-40-3P; 561304-42-5P; 561304-47-0P; 561304-49-2P; 561304-51-6P; 561304-55-0P; 561304-57-2P; 561304-58-3P; 561304-59-4P; 561304-60-7P Role: RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (prepn. of functionalized anilines, aminobenzoic acids and benzodiazepinones via regioselective metalation/electrophilic substitution of trifluoromethoxy-substituted anilines); 83265-56-9P; 220107-38-0P; 307989-56-6P; 505084-60-6P; 561304-41-4P; 561304-43-6P; 561304-44-7P; 561304-45-8P; 561304-46-9P; 561304-48-1P; 561304-50-5P; 561304-56-1P; 561304-61-8P Role: SPN (Synthetic preparation), PREP (Preparation) (prepn. of functionalized anilines, aminobenzoic acids and benzodiazepinones via regioselective metalation/electrophilic substitution of trifluoromethoxy-substituted anilines); 561304-54-9P Role: RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (redn.; prepn. of functionalized anilines, aminobenzoic acids and benzodiazepinones via regioselective metalation/electrophilic substitution of trifluoromethoxy-substituted anilines)
Record creation date
2006-03-03
