This review provides insights into the in situ generated radicals triggered carbon–carbon bond cleavage reactions.

Aliphatic azides are a versatile class of compounds found in a variety of biologically active pharmaceuticals. These compounds are also recognized as useful precursors for the synthesis of a range of nitrogen-based scaffolds of therapeutic drugs, biologically active compounds, and functional materials. In light of the growing importance of aliphatic azides in both chemical and biological sciences, a vast array of synthetic strategies for the preparation of structurally diverse aliphatic azides have been developed over the past decades. However, to date, this topic has not been the subject of a dedicated review. This review aims to provide a concise overview of modern synthetic strategies to access aliphatic azides that have emerged since 2010. The discussed azidation reactions include (a) azidation of C–C multiple bonds, (b) azidation of C–H bonds, (c) the direct transformation of vinyl azides into other aliphatic azides, and (d) miscellaneous reactions to access aliphatic azides. We critically discuss the synthetic outcomes and the generality and uniqueness of the different mechanistic rationale of each of the selected reactions. The challenges and potential opportunities of the topic are outlined.

Conspectus Over recent decades, N-sulfonylhydrazones have attracted significant attention in academic and industrial contexts owing to their ease of preparation, versatile reactivity, high stability, and practicality. In particular, the use of N-sulfonylhydrazones as precursors for diazo compounds has paved the way for innovative and original organic reactions that are otherwise difficult to achieve. Three key developments are noteworthy in the history of N-sulfonylhydrazone chemistry: (1) Bamford and Stevens initially disclosed the application of N-tosylhydrazones as a diazo source in 1952; (2) Aggarwal and co-workers investigated N-tosylhydrazone salts as diazo precursors for sulfur ylide-mediated asymmetric epoxidation and aziridination in 2001; and (3) Barluenga, Valdés and co-workers first reported Pd-catalyzed cross-coupling reactions with N-tosylhydrazones in 2007, thus introducing the direct use of N-tosylhydrazones in carbene transfer reactions. In the past 2 decades, the synthetic exploration of N-sulfonylhydrazones in carbene chemistry has increased remarkably. N-Tosylhydrazones are the most commonly used N-sulfonylhydrazones, but they are not easy to decompose and normally need relatively high temperatures (e.g., 90–110 °C). Temperature, as a key reaction parameter, has a significant influence on the selectivity and scope of organic reactions, especially the enantioselectivity. Aggarwal and co-workers have addressed this issue by using N-tosylhydrazone salts and achieved a limited number of asymmetric organic reactions, but the method is greatly limited because the salts must be freshly prepared or stored in the dark at −20 °C prior to use. Hence, easily decomposable N-sulfonylhydrazones, especially those capable of decomposing at low temperature, should open up new opportunities for the development of N-sulfonylhydrazone chemistry. Since 2014, our group has worked toward this goal and eventually identified N-2-(trifluoromethyl)­benzenesulfonylhydrazone (i.e., N-triftosylhydrazone) as an efficient diazo surrogate that can decompose at temperatures as low as −40 °C. This allowed us to carry out a range of challenging synthetic transformations and to broaden the applications of some known reactions of great relevance. In this Account, we report our achievements in the application of N-triftosylhydrazones in carbene chemistry. On the basis of the reaction types, such applications can be categorized as (i) C­(sp3)–H insertion reactions, (ii) defluorinative reactions of fluoroalkyl N-triftosylhydrazones, (iii) cycloaddition reactions with alkenes and alkynes, and (iv) asymmetric reactions. Additional applications in Doyle–Kirmse rearrangements and cross-coupling with isocyanides (ours) and benzyl chlorides (from the group of Xia) are also summarized in this Account concerning miscellaneous reactions. In terms of reaction efficiency, selectivity, and functional group tolerance, N-triftosylhydrazones are generally superior to traditional N-tosylhydrazones because of their easy decomposition. Mechanistic inv...

A catalyst-dependent chemoselective one-carbon insertion of diazo compounds into the C-C or C-H bonds of 1,3-dicarbonyl species is reported. In the presence of silver(I) triflate, diazo insertion into the C(=O)-C bond of the 1,3-dicarbonyl substrate leads to a 1,4-dicarbonyl product containing an all-carbon α-quaternary center. This reaction constitutes the first example of an insertion of diazo-derived carbenoids into acyclic C-C bonds. When instead scandium(III) triflate was applied as the catalyst, the reaction pathway switched to formal C-H insertion, affording 2-alkylated 1,3-dicarbonyl products. Different reaction pathways are proposed to account for this powerful catalyst-dependent chemoselectivity.

Sulfinyl radicals – one of the fundamental classes of S-centered radicals – have eluded synthetic application in organic chemistry for over 60 years, despite their potential to assemble valuable sulfoxide compounds. Here we report the successful generation and use of sulfinyl radicals in a dual radical addition/radical coupling with unsaturated hydrocarbons, where readily-accessed sulfinyl sulfones serve as the sulfinyl radical precursor. The strategy provides an entry to a variety of previously inaccessible linear and cyclic disulfurized adducts in a single step, and demonstrates tolerance to an extensive range of hydrocarbons and functional groups. Experimental and theoretical mechanistic investigations suggest that these reactions proceed through sequential sulfonyl and sulfinyl radical addition.