One-Pot Synthesis of 2,4-Diacyl Thiophenes from α-Oxo Ketene Dithioacetals and Propargylic Alcohols

Abstract

Although thiophenes having various functionalities are the basic structural units in numerous bioactive compounds and optoelectronic materials, synthetic routes to acylated thiophenes from aliphatic sulfur-containing starting materials are still rare. In particular, there have been no reports concerning the straightforward synthesis of 2,4-diacylthiophenes from alkynes. Herein, we describe a highly efficient and metal-free three-step one-pot synthetic approach to tetrasubstituted 2,4-diacylthiophenes from propargylic alcohols and α-oxo ketene dithioacetals. This research features a relay catalysis system that integrates Brønsted acid-catalyzed propargylation, molecular iodine-mediated electrophilic cyclization, and visible light-induced deiodinative oxygenation. The 2,4-diacylthiophenes serving as the key starting materials are readily synthesized, enabling facile construction of analogues of related biologically active compounds and the modular assembly of tetrasubstituted thienothiophenes.

Visible-Light-Induced Formation of Thiavinyl 1,3-Dipoles: A Metal-Free [3+2] Oxidative Cyclization with Alkynes as Easy Access to Thiophenes

“…68−70 In addition, thieno[2,3-b]thiophene 11 was achieved when 3a was treated with ethyl diazoacetate in the presence of Cu(OTf) 2 (Scheme 6c). 14 In conclusion, a visible-light-induced catalytic [3+2] oxidative cyclization of alkynes with ketene dithioacetals under very mild metal-free conditions without using a base or an oxidant was developed. We found that the easily available ketene dithioacetals can be activated to form a thiavinyl 1,3dipole equivalent.…”

“…Heterocyclizations are powerful tools for the synthesis of five-membered heterocycles − that are often found in natural products , and synthetic pharmaceuticals − and widely used in material science and organic synthesis. − Recent studies revealed that oxidative heterocyclizations − could evoke novel and useful catalytic transformations, which otherwise are difficult to achieve. For example, the cyclization of ketene dithioacetals, − a kind of electron-rich olefin, under electrochemical conditions afforded the cyclic amino acid derivatives (Scheme a, X = NH) .…”

“…To the best of our knowledge, there have been few studies on the photoredox reactions of ketene dithioacetals and the studies have been limited to the coupling reactions with aryldiazonium salts or alkenes or need an other photo-redox-active reactant . There have been few reports about the visible-light-mediated synthesis of thiophenes, − ,− with some syntheses of benzothiophenes from alkynes with o -methylthio-arene diazonium salts or 2-halothioanisoles. − We are glad to see that our proposed [3+2] oxidative cylization of ketene dithioacetals and alkynes (Scheme b) could proceed smoothly under extremely simple and mild reaction conditions without using base, acid or oxidants. − Clearly, α-acyl ketene dithioacetals were activated by visible light to form a previously unknown thiavinyl 1,3-dipole intermediate that thus initiates this [3+2] cyclization.…”

“…Furthermore, the transformations of the multisubstituted thiophenes were tested. In the presence of TiCl 4 and Zn, the reduction of thiophene 3a gave 2,4-disubstituted thiophenes 10 , instead of the expected McMurry cyclization product. − In addition, thieno­[2,3- b ]­thiophene 11 was achieved when 3a was treated with ethyl diazoacetate in the presence of Cu­(OTf) 2 (Scheme c) …”

Selectfluor-Promoted Intramolecular N–S Bond Formation of α-Carbamoyl Ketene Dithioacetals in the Presence of Water: Synthesis of Multifunctionalized Isothiazolones

“…Selectfluor is not only a powerful fluorination reagent commercially available but also recognized as an exceptionally stable, nonvolatile, nonhygroscopic, and mild oxidant, which has been extensively used for efficient construction and site-selective C–H direct functionalization of heterocyclic molecules. , On the other hand, ketene dithioacetals, as versatile building blocks, permit the rapid assembly of structurally diverse carbo-/heterocyclic architectures through different cycloaddition or annulative coupling reaction processes . Following our continuous interest in selectively developing a new cyclic backbone based on them, we here described a metal-free Selectfluor-mediated direct synthesis of highly functionalized isothiazolones from easily synthesized α-carbamoyl ketene dithioacetals involving intramolecular N–S bond formation.…”