The direct methylation of N-heterocycles is an important transformation for the advancement of pharmaceuticals, agrochemicals, functional materials, and other chemical entities. Herein, the unprecedented C(sp 2)-H methylation of iminoamido heterocycles as nucleoside base analogues is described. Notably, trimethylsulfoxonium salt was employed as a methylating agent under aqueous conditions. A wide substrate scope and excellent level of functional-group tolerance were attained. Moreover, this method can be readily applied to the site-selective methylation of azauracil nucleosides. The feasibility of gram-scale reactions and various transformations of the products highlight the synthetic potential of the developed method. Combined deuterium-labeling experiments aided the elucidation of a plausible reaction mechanism. Scheme 1. CÀH methylation of N-heterocycles.

A redox-neutral C2-selective methylation of heterocyclic N-oxides with sulfonium ylides is described herein. This report presents unprecedented findings for the utility of sulfonium ylides as the methylation source of N-heterocycles beyond the Corey–Chaykovsky reaction. Intriguingly, pyrrolidine plays a significant role in minimizing the reductive C2-methylation process. This method is characterized by its mild conditions, simplicity, and excellent site selectivity. The applicability of the developed protocol is showcased by the late-stage methylation and sequential transformations of complex drug molecules.

The rhodium(III)-catalyzed spiroannulation reaction between N-aryl indazol-3-ols and maleimides is described herein. The developed method is showcased by the construction of spirosuccinimides using bioactive molecule-linked and chemical probe-linked maleimides. Combined...

The Rh(III)-catalyzed C−H functionalization and subsequent intramolecular cyclization between azobenzenes and vinylene carbonate is described herein. Depending on the electronic property of azobenzenes, this transformation results in the formation of (2H)-indazoles or dihydrocinnolin-4-ones through the generation of ortho-alkylated azo-intermediates followed by decarboxylation. Surprisingly, vinylene carbonate acts as an acetaldehyde or acetyl surrogate to enable the [4 + 1] or [4 + 2] annulation reaction. This transformation is characterized by its mild reaction conditions, simplicity, and excellent functional group compatibility.

The synthesis of alkylated diazine derivatives is important for their practical utilization as pharmaceuticals and for other purposes. Herein, we describe the metal-free siteselective C−H alkylation of diazine N-oxides using phosphonium ylides that affords a variety of alkylated diazine derivatives with broad functional group tolerance. The utility of this method is showcased by the late-stage functionalization of a commercially available drug such as varenicline. Notably, the sequential C−H alkylation of pyrazine N-oxides for the total synthesis of a pyrazine-containing natural product, paenibacillin A, highlights the importance of this method.