Electrochemically Enabled Dehydrogenative Phosphorothiolation of 2H‐Indazoles under Electrolyte‐Free Conditions

Abstract

We have developed an electrochemical method for phosphorothiolation of 2H-indazoles using S-hydrogen phosphorothioates via cross dehydrogenative coupling reaction under metal-free and electrolyte-free conditions. This protocol is compatible with electron donating groups like À Me, À OMe, halogen and elctron withdrawing groups such as À COOEt, affording respective indazolyl phosphorothioates in 62%-91% yields. Comprehensive mechanistic studies indicate that the reaction proceeds through a radical pathway.

Recent Advances in the Direct Synthesis of Sulfur‐Containing Organophosphorus Compounds via Radical Processes

“…A variety of other (hetero)arenes, such as indoles, pyrroles, thiophenes, trimethoxybenzene, and N,Ndimehylaniline were all suitable for this novel transformation, and the corresponding products were obtained in moderate to excellent yields. Mechanistically, the radical cation 36-A, generated by electroxidation of imidazo [1,5-a] More recently, Hajra's group [52] developed an efficient electro-promoted phosphprothiolation of 2Hindazoles 82 with S-hydrogen phosphorothioates 83 via cross-dehydrogenative coupling reaction under conditions, affording a series of indazolyl phosphorothioates 84 with moderate to excellent yields (Scheme 37). This novel transformation has been performed under metal-free and electrolyte-free conditions with good functional group compatibility.…”

Electrochemical C–H Sulfonylation of Hydrazones

“…In the C/Pt system, the reaction proceeded well but it was not as good as in the C/C system. 4,15 For the other two systems, a sharp declining yield of the transformation was observed. With the employment of 1 and 4 equiv of 2a, the product yields were obtained in 55% and 83% yield, respectively (Table S3, entry 19).…”

“…Therefore, we planned to develop a supporting electrolyte-free electrochemical synthetic protocol. Although some electrochemical reactions under electrolyte-free conditions have been reported, they are relatively rare. ,, In continuation of our previous work, we focused on supporting electrolyte-free electrochemical sulfonylation by judicious selection of using sodium sulfinate as the sulfonylating agent because it can be used as the reagent as well as the supporting electrolyte.…”

“…Hence, the C–H transformations of hydrazones have been successfully achieved by many groups using various strategies such as metal-free, metal-catalyzed, photocatalyzed (Scheme a), etc., and also the phosphorylation, trifluoromethylation, and amination of hydrazones were performed by electrochemical methods (Scheme b) . Encouraged by our previous work on hydrazone and electro-organic synthesis, herein we report the electrochemical sulfonylation of hydrazones under electrolyte-free conditions (Scheme c). To the best of our knowledge, no alternative method for the sulfonylation of hydrazone derivatives has been reported in the literature.…”

Metal-free direct C–H phosphonation of N-heterocycles with diphenylphosphine oxides under mild conditions

“…However, explosive peroxides, specialized electrodes or photocatalysts still are necessary. [41][42][43][44][45][46][47][48][49][50][51][52][53][54][55] In order to continuously pursue easy operation and concise reaction conditions and expand the scope of C-H functionalization of 1,2,4-triazine-3,5(2H,4H)-diones, we have developed DBU promoted phosphonation of 1,2,4-triazine-3,5(2H,4H)-diones to construct a C-P bond via atom and step-economical C(sp 2 )-H/P-H oxidative cross-dehydrogenative-coupling (Scheme 1d). The present method features several advantages: (1) inexpensive and readily available DBU emerges as the promoter, rather than a toxic/expensive metal catalyst contaminating the products and imposing restrictions on their subsequent application in the pharmaceutical industry; (2) more significantly, dimethyl carbonate (DMC) can be directly used as a solvent, as we know one of the critical principles of green chemistry is the usage of a safer solvent; (3) ambient inexhaustible air is used as the only terminal oxidant; (4) after completion of the reaction, the product was isolated via simple extraction, washing and filtration, but column chromatography was not required, making it a potential method for industrial applications; and (5) our technology is reproducible on a gram-scale reaction affording a clean product in a reproducible yield, and a variety of N-heterocycles including 1,2,4-triazine-3,5(2H,4H)-diones, quinoxalin-2(1H)-ones, quinoxalines, pyrazinones and even substrates with medicinal molecule frameworks are compatible in this phosphonation.…”