The hexafluoroisopropanol (HFIP)-assisted thermal denitrogenative fragmentation of areneazo-2-(2-nitro)propanes enabled heteroarylation of functionalized alkenes through cooperative radical and redox processes. Bench-stable areneazo-2-(2-nitro)propanes served as versatile aryl radical precursors for carboheterocyclization with alkenyl esters, affording diverse arylated lactones and heterocycles with broad functional group tolerance. Mechanistically, the radical fragmentation–nitro–nitrite isomerization of areneazo-2-(2-nitro)propanes generated nitric oxide that underwent a redox process with tertiary radical intermediates to promote heterocyclization. The oxidant-free conditions generated dinitrogen and acetone as benign byproducts.
Herein, we report a novel strategy to construct bridged benzo[1,3,6]oxadiazocine scaffold from γ-hydroxy enals and o-phenylenediamine, a transformation that diverges from the conventional benzimidazole formation via aldehyde 1,2-addition. This protocol features unprecedented reactivity, green conditions (water solvent, 1 mol % catalyst, room temperature), simple operations, broad substrate scope, and versatile product derivatization, providing a practical and sustainable route to three-dimensional scaffolds of potential value in medicinal chemistry.
Twenty new lanostane triterpenoids, kadsuracoccinins A–T (1–20, respectively), were isolated from the stems of Kadsura coccinea, with compounds 1–7 constituting four new carbon scaffolds elucidated by NMR analysis, X-ray diffraction, GEMSTONE-NOE-aided fc-rDG/DDD, and ECD calculations. Luciferase-refolding, NMR STD, and SPR assays revealed compounds 4 and 8–10 as the first lanostane-type Hsp90 inhibitors, which bind Hsp90 through non-N-terminal modes, with compound 8 exhibiting a K D of 4.04 μM.
A metal- and oxidant-free synthesis of ortho-amidinated naphthol esters from readily available N-naphthylhydroxylamines and amides has been developed using fluorosulfuryl imidazolium triflate under mild conditions. This transformation provides a broad range of products in good yields with excellent ortho selectivity and broad functional group tolerance. A scale-up experiment further demonstrates the practicality of the protocol. Notably, this tandem process enables concurrent C1 esterification and ortho amidination of the naphthalene framework, providing an efficient strategy for the difunctionalization of naphthalene derivatives. The densely functionalized products obtained through this method may serve as useful building blocks in medicinal chemistry and organic synthesis.
The development of transient directing groups that are generated and erased in situ has created new opportunities for catalytic C–H functionalization. This study reported a Rh(III)-catalyzed cascade annulation of readily available amidinium salts 1 or ethyl benzimidates 2 with 2-diazoindane-1,3-diones 3, providing functionalized indeno[1,2-c]isoquinolines (IIQLs) 6 and 7. This transformation integrated C–H activation, carbene insertion, and intramolecular cyclization into a single catalytic sequence. The resulting products subsequently underwent a second Rh(III)-catalyzed [4 + 2] annulation with diarylalkynes 4 or 2-diazoketones 5, furnishing structurally complex pentacyclic frameworks 8. Mechanistic studies suggest that Lewis acid-promoted amino–imine tautomerization accompanied by double-bond migration generated a transient imine from the embedded 2-aminopyridine-type motif. This substrate-derived imine directed o-aryl C(sp2)–H activation and was subsequently erased, eliminating the need for the installation and removal of permanent directing groups as well as the use of external transient directing agents. Overall, this modular strategy enabled the efficient construction of densely fused heterocyclic architectures by combining indane-1,3-dione and isoquinoline scaffolds, providing a versatile platform for the synthesis of structurally sophisticated molecules with potential applications in medicinal chemistry.
