Substituted pyrrolidine derivatives are obtained via regio- and chemoselective 5-exo-dig radical cyclization of unactivated 1,6-enynes with chalcogens under metal- and oxidant-free conditions.

A new synthetic protocol has been developed for the synthesis of N‐formamide derivatives using ethers as a C1 synthon under metal‐free reaction conditions. The reaction is proposed to proceed through C−H functionalization, C−O cleavage, and C−N bond formation. This protocol is applicable to a variety of primary amines resulting in N‐formamides in moderate to good yields. 1,4‐dioxane was chosen as best C1 synthon after screening with various ethers. Mechanistic studies disclosed that the reaction proceeds through a radical pathway. While using α‐amino ketones a α‐alkylation product was formed rather than formylation. By replacing dioxane with Tetramethylethylenediamine (TMEDA) under standard conditions also gave the N‐formamide derivatives in moderate yields.magnified image

The radical chemistry of ynamides has recently drawn the attention of synthetic organic chemists to the construction of various N-heterocyclic compounds. Nevertheless, the ynamide-radical chemistry remains a long-standing challenge for chemists due to its high reactivity, undesirable byproducts, severe inherent regio- and chemoselective problems. Importantly, the ynamide C(sp)-N bond fission remains an unsolved challenge. In this paper, we observe Photoinduced radical trigger regio- and chemoselective ynamide bond fission, structural reshuffling and functionalization of 2-alkynyl-ynamides to prepare synthetically inaccessible/challenging chalcogen-substituted indole derivatives with excellent step/atom economy. The key breakthroughs of this work includes, ynamide bond cleavage, divergent radical precursors, broad scope, easy to handle, larger-scale reactions, generation of multiple bonds (N-C(sp2), C(sp2)-C(sp2), C(sp2)-SO2R/C-SR, and C-I/C-Se/C-H) in a few minutes without photocatalysts, metals, oxidants, additives. Control experiments and 13C-labeling experiments supporting the conclusion that sulfone radicals contribute to ynamide structural reshuffling processes via a radical pathway.

Oximes have been identified as reusable templates for the synthesis of ureas and carbamates by anin situgeneration of carbamoyl oximes under metal-free conditions.

The FeCl3-promoted ring size-controlled oxidative activation of o-alkynylanilines opens up a complementary appealing protocol for poly-N-heterocycle synthesis.

We developed time-atom economic regio-and chemoselective sulfonyl radical triggered 5-exo-dig cyclization of unactivated 1,6-enynes with sulfonyl halides under metal, additive-free reaction conditions to achieve highly substituted five-membered heterocyclic compounds. This transformation creates three new bonds, such as CÀ SO 2 , CÀ C, and active CÀ I/ Br bonds. Importantly, one-pot protocols produce desired products directly from sodium sulfinates and have an additional advantage such as minimising chemical waste, saving time, and simplifying practical aspects compared to existing protocols.

A new synthetic methodology has been developed to prepare the biologically important azepino[4,5-b]indole derivatives under Brønsted acid catalysis. The notable features of this protocol include its operational simplicity, high reaction yields and environmentally benign and mild reaction conditions.

The development of a method for performing radical initiated intramolecular cascade cyclization of 1,n-enynes provided a competent protocol for producing structurally diverse complex heterocycles.