Search

The trifluoromethyl group is widely recognized for its significant role in the fields of medicinal chemistry and material science due to its unique electronic and steric properties that can alter various physiochemical properties of the parent molecule, such as lipophilicity, acidity, and hydrogen bonding capabilities. Compared to the well-established C-trifluoromethylation, N-trifluoromethylation has received lesser attention. Considering the extensive contribution of nitrogen to drug molecules, it is predicted that constructing N-trifluoromethyl (N-CF3) motifs will be of great significance in pharmaceutical and agrochemical industries. This review is mainly concerned with the synthesis of heterocycles containing this motif. In three-membered heterocycles containing the N-CF3 motif, the existing literature mostly demonstrated the synthetic strategy, as it does for four- and larger-membered heterocycles. Certain structures, such as oxaziridines, could serve as an oxidant or building blocks in organic synthesis. In five-membered heterocycles, it has been reported that N-CF3 azoles showed a higher lipophilicity and a latent increased metabolic stability and Caco-2-permeability compared with their N-CH3 counterparts, illustrating the potential of the N-CF3 motif. Various N-CF3 analogues of drugs or bioactive molecules, such as sildenafil analogue, have been obtained. In general, the N-CF3 motif is developing and has great potential in bioactive molecules or materials. Give the recent development in this motif, it is foreseeable that its synthesis methods and applications will become more and more extensive. In this paper, we present an overview of the synthesis of N-CF3 heterocycles, categorized on the basis of the number of rings (three-, four-, five-, six- and larger-membered heterocycles), and focus on the five-membered heterocycles containing the N-CF3 group. [ABSTRACT FROM AUTHOR]

We developed a facile, efficient method for synthesizing highly substituted 2‐aminopyridines from unstable vinyl carbodiimides generated in situ in a one‐pot transformation. A series of novel highly substituted 3‐functionalized 2‐aminopyridines were produced in good yields. Reaction mechanism studies, which included control experiments and density‐functional theory (DFT) calculations, demonstrated that Rh and potassium carbonate played key roles in the cyclization step. [ABSTRACT FROM AUTHOR]

Isocyanates are widely applied in the fields of materials science, drug discovery and chemical industry processes. Palladium-catalyzed carbonylation of azides with carbon monoxide (CO) is reported as a powerful method for simple and efficient access to isocyanates, which are important precursors for preparing structurally meaningful urea, carbamate and amidine derivatives. In this account, we provide an overview on the synthesis of isocyanates and their subsequent reactions to obtain diverse nucleophilic addition products. In addition, with particular emphasis on our mechanistic studies of the Pd-catalyzed carbonylation process, we outline the identification of the actual catalytic species, the possible intermediates and some key factors in the catalytic cycle. 1 Introduction 2 Palladium-Catalyzed Reaction of Azides with CO and Subsequent Nucleophilic Additions 3 Mechanistic Studies on the Palladium-Catalyzed Reaction of Azides with CO 3.1 Studies on the Actual Catalytic Species and the Key Intermediates in the Activation and Carbonylation of Acyl Azides 3.2 Study of the Sulfonylurea Product Self-Catalyzed Carbonylation of Sulfonyl Azides 3.3 Study of the Actual Catalytic Pattern of the Pd/C Catalyst 4 Conclusion [ABSTRACT FROM AUTHOR]

N-Functionalized C-fluoroalkyl amidines are attracting great attention due to their potential in pharmaceuticals. Herein, we report a Pd-catalyzed tandem reaction of azide with isonitrile and fluoroalkylsilane via a carbodiimide intermediate, providing facile access to N-functionalized C-fluoroalkyl amidines. This protocol offers an approach toward not only N-sulphonyl, N-phosphoryl, N-acyl, and N-aryl but also C-CF 3 , C 2 F 5 , and CF 2 H amidines with a broad substrate scope. The accomplishment of further transformations and Celebrex derivatization in gram scale and biological evaluation reveals the important utility of this strategy.

We developed a facile, efficient method for synthesizing highly substituted 2-aminopyridines from unstable vinyl carbodiimides generated in situ in a one-pot transformation. A series of novel highly substituted 3-functionalized 2-aminopyridines were produced in good yields. Reaction mechanism studies, which included control experiments and density-functional theory (DFT) calculations, demonstrated that Rh and potassium carbonate played key roles in the cyclization step., (© 2022 Wiley-VCH GmbH.)