Ruthenium-Catalyzed Chemoselective N–H Bond Insertion Reactions of 2-Pyridones/7-Azaindoles with Sulfoxonium Ylides

Organosulfur compounds have long played a vital role in organic chemistry and in the development of novel chemical structures and architectures. Prominent among these organosulfur compounds are those involving a sulfur(IV) center, which have been the subject of countless investigations over more than a hundred years. In addition to a long list of textbook sulfur-based reactions, there has been a sustained interest in the chemistry of organosulfur(IV) compounds in recent years. Of particular interest within organosulfur chemistry is the ease with which the synthetic chemist can effect a wide range of transformations through either bond formation or bond cleavage at sulfur. This review aims to cover the developments of the past decade in the chemistry of organic sulfur(IV) molecules and provide insight into both the wide range of reactions which critically rely on this versatile element and the diverse scaffolds that can thereby be synthesized.

Human immunodeficiency virus (HIV) infection is now pandemic. Targeting HIV-1 reverse transcriptase (HIV-1 RT) has been considered as one of the most successful targets for the development of anti-HIV treatment. Among the HIV-1 RT inhibitors, non-nucleoside reverse transcriptase inhibitors (NNRTIs) have gained a definitive place due to their unique antiviral potency, high specificity, and low toxicity in antiretroviral combination therapies used to treat HIV. Until now, >50 structurally diverse classes of compounds have been reported as NNRTIs. Among them, six NNRTIs were approved for HIV-1 treatment, namely, nevirapine (NVP), delavirdine (DLV), efavirenz (EFV), etravirine (ETR), rilpivirine (RPV), and doravirine (DOR). In this perspective, we focus on the six NNRTIs and lessons learned from their journey through development to clinical studies. It demonstrates the obligatory need of understanding the physicochemical and biological principles (lead optimization), resistance mutations, synthesis, and clinical requirements for drugs.

This Tutorial Review highlighted recent achievements on the catalytic cyclization reactions of sulfur ylide reagents, especially the asymmetric processes avoiding the use of structurally complex chiral sulfides. Great achievements in the asymmetric cyclization reactions of sulfur ylides have been reached by using chiral sulfides; however, this method usually suffers from the high loading of chiral sulfides. Over the past decade, new catalysis technologies beyond chiral sulfide-based catalysis have been gradually applied to the cyclizations of sulfur ylides. These technologies, including organocatalysis, organometallic catalysis and photocatalysis, can avoid the use of stoichiometric chiral pools and enable the development of new cyclization reactions of sulfur ylides. In this tutorial review, recent advances in this rapidly developing field will be highlighted with particular emphases on the catalytic mechanism and the development of new reactions, new reagents and new concepts.