Na_(2)CO_(3)催化的叠氮三甲基硅烷对δ-三氟甲基-δ-芳基取代对亚甲基苯醌的1,6-共轭加成:高效构建含三氟甲基和叠氮取代的二芳基甲烷化合物

Na_(2)CO_(3)-catalyzed 1,6-Conjugate Addition of Trimethylsilyl Azide to δ-CF_(3)-δ-Aryl-disubstituted Para-Quinone Methides:Efficient Construction of Diarylmethanes Bearing CF_(3)-and N_(3)-Substituted Quaternary Stereocenters

报道了一种高效的δ-三氟甲基-δ-芳基-取代对亚甲基苯醌的叠氮化芳基化反应.以Na_(2)CO_(3)为催化剂,叠氮三甲基硅烷与δ-三氟甲基-δ-芳基取代对亚甲基苯醌发生1,6-共轭加成反应,以优异的分离产率(90%~96%)获得了结构多样的含有三氟甲基和叠氮取代的二芳基甲烷化合物.该反应具有良好的底物适用范围和官能团兼容性.

Organic azides have emerged as significant and versatile reactants in organic synthesis and have been widely used in the field of chemical biology,pharmaceutical discovery,and materials science.Trifluoromethylated compounds were recognized as key structural motifs in bioactive molecules and synthetic pharmaceuticals.The incorporation of a trifluoromethyl group into organic molecules is often beneficial for improving their physiochemical properties such as metabolic stability,lipophilicity,and bioavailability.As a consequence,the development of efficient methods for the synthesis of molecules containing both the trifluoromethyl group and the azide group is highly desired.However,only a few of synthetic methods were reported for the synthesis of these structures.On the other hand,diarylmethane derivatives spread across natural products,pharmaceuticals and functional materials,and their synthesis was attracted great attention owning to the diverse biological and medical properties.Described is an efficient azidative aromatization process ofδ-CF_(3)-δ-aryl-disubstituted para-quinone methides with trimethylsilyl azide.Using Na_(2)CO_(3)as catalyst,1,6-conjugate addition of trimethylsilyl azide toδ-CF_(3)-δ-aryl-substituted para-quinone methides went smoothly,delivering diarylmethanes bearingδ-CF_(3)-and N3-substituted stereocenters in excellent yields.Moreover,the reaction displays a broad substrate scope and excellent functional group tolerance.