Carboxylation Of Aromatic Compounds And Trifluoromethoxylation & Trifluoromethylation Of N-heteroaromatic Compounds

A novel approach for palladium-catalyzed ethoxycarbonylations of aryl boronic acids using diethylpyrocarbonate as CO/CO₂ surrogate in moderate to good yields was investigated; The first metal-free one-step method for synthesis of ortho-N-heteroaromatic trifluoromethoxyl derivatives by site-specific O-CF₃ bond formation using N-heteroaromatic phenols and Togni’s reagent is described; A general and reliable method for the synthesis of trifluoromethyl group-containing N-heteroaromatics through highly regioselective addition of a trifluoromethyl nucleophile of CF₃ TMS with N-heteroaromatic N-oxides which was activated by trimethyloxonium tetrafluoroborate was investigated.1. Palladium-Catalyzed Carbonylations of Aryl Boronic Acids:Facile Synthesis of Arylcarboxylic Acid Ethyl EstersA novel approach for palladium-catalyzed ethoxycarbonylations of aryl boronic acids using diethylpyrocarbonate as CO/CO₂ surrogate using 5 mol % Pd（OAc）2 as catalyst, 20 mol % PPh3 as ligand, Na2CO3 as base, dioxane as solvent in moderate to good yields was investigated（Scheme 1）. This method has broad functional group compatibility（such as fluoro, chloride, cyano, trifluoromethyl, ether, ester, alcohols, ketones, and aldehyde）. It offers a convenient alternative for ethoxycarbonylation compared to conventional carbonylations using syngas or CO/CO₂ directly and avoiding the use of high-pressure equipment. We believe this work can be widely utilized in pharmaceutical research to build many interesting pharmaceutical scaffold.2. Metal-free Highly Regioselective Synthesis of N-heteroaromatic Trifluoromethoxyl Compounds by Direct O-CF₃ Bond FormationThe first Metal-free one-step method for synthesis of ortho-N-heteroaromatic trifluoromethoxyl derivatives by site-specific O-CF₃ bond formation using N-heteroaromatic phenols and Togni’s reagent, CH3NO₂ as solvent is described（Scheme 2）. The approach enables the unprecedented syntheses of a wide range of six or five-membered N-heteroaromatic trifluoromethoxyl compounds containing one or two heteroatoms from most commonly used N-heteroaromatic phenols. The notable advantage of the protocol is simple and mild, needless metal and toxic reagents, and compatible with a variety of functional groups（such as cyano, ether, ester, halide, acetyl, alkyl and aryl et al.）. What is more, it especially suitable for the larger scale application. We believe this work can be useful in industrial processes, laboratory methods, and widely utilized in pharmaceutical research to build many interesting pharmaceutical scaffold.3. Metal-free Highly Regioselective Synthesis of N-heteroaromatic Trifluoromethyl Compounds Using CF₃TMSA general and reliable method for the synthesis of trifluoromethyl group-containing N-heteroaromatics through highly regioselective addition of a trifluoromethyl nucleophile of CF₃ TMS with N-heteroaromatic N-oxides which was activated by trimethyloxonium tetrafluoroborate was investigated（Scheme 3）. Noteworthy characteristics of the developed reaction are as follows:（1） CF₃ TMS is wieldy used and inexpensive,（2） the regioselective trifluoromethylation proceeded smoothly without using any transition metal catalysts or toxic reagents,（3） the reaction which started from non-oxidized N-heteroaromatic compounds could reacted smoothly under mild conditions and with high functional group tolerance to get the regioselective trifluoromethylation of N-heteroaromatics. This method will be useful in both laboratory and industrial processes. The unique characteristics of N-heteroaromatic [N-oxide–OMe]BF4 complexes will be generally useful for regioselective introduction of othernucleophiles to N-heteroaromatic compounds.