Photoinduced ynamide structural reshuffling and functionalization

Abstract

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.

Photoinduced Radical Cyclization of 1,6‐Diynes: Rapid Access to Highly Substituted Carbocyclic and Heterocyclic Compounds

“…To elucidate the exact role of blue LED light, we measured the blue LED emission spectrum for a 40‐W Kessil blue LED lamp (Figures S4 and S5). Furthermore, we obtained the absorption spectra for the radical precursors 2 a and 2 e in 10 −2 –10 −5 M of the solvent dichloromethane (DCM) (Figures S6−S13) [12b,c] . Both 2 a and 2 e showed visible light absorption peaks for the blue LED light source, suggesting that the blue LED light initiates radical formation.…”

“…Based on the above control experiments, data from the literature, [3f,4f,15–16] and our previous work, [12] we suggest a plausible reaction mechanism, as shown in Scheme 6. First, 4‐methylbenzenesulfonyliodide ( 2 a ) absorbs blue LED light to produce sulfonyl ( 2 a’ ) and iodine ( 2 a” ) radicals via homolytic bond fission [12b,c] . The reactive sulfonyl radical then attacks 1 a to produce the vinyl radical intermediate A , which simultaneously produces the another vinyl radical intermediate B via 6‐ exo ‐dig cyclization with another 1 a alkyne.…”

Synthesis of β-iodovinyl sulfonesviadirect photoinitiated difunctionalization of internal alkynes

“…[17][18][19][20][21][22] The development of methods for synthesis of sulfones has recently attracted the attention of many researchers. [23][24][25][26][27][28] One of the most efficient methods for creating a C-SO 2 bond to obtain vinyl sulfones is the alkyne sulfonylation reaction is the addition of a sulfonyl radical to an alkyne.…”

Ynamides in Radical Reactions: A Route to Original Persubstituted 2-Aminofurans

“…With regard to radical chemistry, ynamides behave as electron rich radical acceptors. Indeed, the relevant literature shows that, if one excepts intramolecular radical additions devised for heterocyclic synthesis, the few reported intermolecular additions to ynamides essentially involve electrophilic sulfanyl radicals . Recently, we have shown that the strategy based on atom transfer radical addition (ATRA) using ethyl α-iodoacetate, α-iodo-acetonitrile, or α-iodo- N,N -diethyl acetamide as a radical precursor is efficient in achieving this transformation.…”