Green Chemistry: the research group of Wu Dalei Irwin reported the electrochemical [4 + 2] cycloaddition reaction catalyzed by cobalt to synthesize sulforamide

Sulforamide is a kind of important heterocyclic compounds It is not only an important precursor in synthetic chemistry, but also a common skeleton in many drugs, agricultural chemicals and bioactive compounds Therefore, the development of efficient and practical methods for the synthesis of sulforamide has been widely concerned In general, sulfonamides are prepared by intramolecular cross coupling or tandem cyclization However, the raw materials of these methods usually need multi-step preparation In recent years, researchers have reported examples of transition metal catalyzed C-H / X-H oxidation and cyclization to prepare sulfolactam However, such reactions require stoichiometric metal oxidants and generate metal by-products, which greatly limits the wide application of the above methods Therefore, it is necessary to develop a simple and practical synthesis method of Sul Recently, Professor Lei Aiwen's research group of Wuhan University reported the first case of electrochemical [4 + 2] cycloaddition of sulfonamide and alkyne catalyzed by transition metal (scheme 1) In this method, cobalt salt was used as a metal catalyst to prepare a series of sulfonated lactam derivatives and release hydrogen in a diaphragm free cell Relevant research results were published on Green Chemistry (DOI: 10.1039/d0gc00289e) (source: Green Chemistry) at first, the author used 4-methyl-n - (quinoline 8-yl) benzenesulfonamide (1) and phenylacetylene (2) as model substrates to study the reaction conditions (Table 1) In an undivided cell, when ethanol and acetic acid are used as mixed solvents and CO (OAC) 2.4h 2O and NaOAc are used for electrolysis, substrate 1 and substrate 2 can obtain [4 + 2] cyclized product 3 (Table 1, entry 1) with 80% separation yield The control experiment shows that power supply, cobalt catalyst and NaOAc are the key factors of the reaction (source: Green Chemistry) under the optimized reaction conditions, the author discussed the universality of the reaction (Table 2) The cyclization products 3 - 9 can be obtained by 73% - 81% of various phenylacetylene, and the electrical properties of substituents have little effect on the yield In addition, alkylalkyne is also compatible with the reaction system, and the product 10 - 19 is obtained in a medium to high yield, and it is resistant to a variety of active functional groups (such as alkenyl, alkynyl, ester, hydroxyl, etc.) Then, the scope of application of sulfonamide substrate was investigated Unfortunately, only electrically neutral substrates can form cyclized product 20 in high yield After that, by reducing the reaction current to 3 Ma or increasing the reaction current to 5 mA, both electron rich and electron deficient substrates should be converted into products 22 - 31 in medium to high yields (source: Green Chemistry) in order to prove the practicability and expansibility of the reaction, the author carried out the gram level reaction of 4-methyl-n - (quinoline-8-yl) benzene sulfonamide (1) and phenyl acetylene (2) The final yield of 1.72 g was 86% (source: Green Chemistry) based on the results of control experiments and previous literature, the author proposed the possible mechanism of the electrochemical [4 + 2] cyclization (scheme 5) Firstly, CO (II) species coordinated with substrate 1 to form CO (II) complex a, and then oxidized with H 2O 2 to form CO (III) complex B Then, under the action of NaOAc, CO (III) complex B is activated by intramolecular C-H to form a cyclic CO (III) complex C Next, phenylacetylene 2 is inserted and deoxidized to form cyclized product 3 and CO (I) species, which are oxidized at the anode to form CO (II) species At the same time, O2 is reduced to superoxide anion (O2 • -), then hydrogen atom is obtained from EtOH, and protons are obtained from Hoac, finally H 2O 2 is obtained (source: Green Chemistry) Summary: the electrochemical [4 + 2] cycloaddition of sulfonamide and alkyne catalyzed by cobalt has been realized for the first time In this reaction, cobalt catalyst was recovered by anodization in a diaphragm free cell, and a series of sulfonamide derivatives were prepared without metal oxidants.