Construction Of α-fluorinated Carboxylic Acids And Pyrrole Compounds By α-functionalization Of Carboxylic Acids

Carboxylic acids are widely found in natural products,drugs,pesticides and materials,and have important applications in organic synthesis.Direct α-functionalization of carboxylic acids represents an efficient protocol for building up structural diverse carboxylic acid compounds.Due to the low acidity of the α-proton of carboxylic acids and the acidity of the carboxylic acid itself,more than two equivalents of strong base are often required to deactivate the carboxylic acid,which makes its application was restricted.In recent years,organic chemists have devoted themselves to the reactions of α-functionalization of carboxylic acids,such as allylation reaction of carboxylic acids at α-position,Aldol reaction with aldehydes,arylation reaction at α-position,etc.This thesis investigates the α-position functionalization of carboxylic acids to construct α-fluorinated carboxylic acids and pyrrole compounds,the specific research contents are as follows:（I）: The catalytic α-C-H fluorination of aryl acetic acid was achieved with good functional tolerance in the presence of a boron catalyst.A series of α-fluoro aryl acetic acids was obtained in a single step with high yields（up to 96%）.The reaction could be performed on gram-scale.Further transformed to construct amides and alcohols.Moreover,the catalytic reaction was employed for the synthesis of bioactive molecules,and modification of some NSAIDs ibuprofen,flurbiprofen,etc.（II）: An Fe（III）-catalyzed Mannich/decarboxylative ring-expansion reaction for the synthesis of pyrrole derivatives.β-Ketoacids were employed as enolate equivalents of a simple ketone and were coupled with 2H-azirine in a formal [3+2] cycloaddition reaction.A series of di-and tri-alkyl/aryl-substituted and fused pyrrole derivatives was obtained in moderate to excellent yields（17-92%）.under mild reaction conditions.The products could be synthesized on gram-scale with 5 mol% catalyst loading.