Highly regioselective para-methylthiolation/bridging methylenation of arylamines promoted by NH₄I

Abstract

Aryl methyl thioethers and methylene-bridged arylamines were synthesized via highly regioselective para-methylthiolation/bridging methylenation of arylamines using DMSO as the methylthio or methylene source in the presence of NH4I under metal-free conditions. For the substrates with both electron-donating and electron-withdrawing substituents, the reaction proceeded smoothly and gave moderate to good yields.

Synthesis of symmetrical methylene-bridged imidazoheterocycles using DMSO as methylene source under metal-free conditions

“…Our previous work confirmed that DMSO may produce methylthio radical in the presence of NH 4 I and the methylthiolation product maybe generated, 16 but no -SCH 3 substituted imidazoheterocycles were detected in the present reaction systems. The deuteriumlabeling experiment confirmed that the methylene group in product 2a completely originated from DMSO (eq 1).…”

“…Our previous work confirmed that DMSO may produce methylthio radical in the presence of NH 4 I and the methylthiolation product maybe generated, 16 but no -SCH 3 substituted imidazoheterocycles were detected in the present reaction systems. 16,18,20 Acid-catalyzed addition of 2-phenylimidazo [1,2a]pyridine (1a) to CH 2 O generated an unstable cation A, 21 followed by elimination of H 2 O to form B. to the model reaction did not affect the yield evidently (eq 2).…”

“…Recently, Yi and Zhang developed a method for the direct trifluoromethylthiolation of indoles with CF 3 SO 2 Na. 16 It is well known that methylene-bridged binary heteroaryls are the key structural motifs in many natural products and bioactive compounds. Further screening showed that both DMSO and diethyl phosphite were essential for the formation of 2a, which revealed that the methylene perhaps stemmed from the interaction of them (Scheme 1).…”

The Applications of Dimethyl Sulfoxide as Reagent in Organic Synthesis

“…Subsequently, Sun and co‐workers reported a highly regioselective para ‐methylthiolation/bridging methylenation of arylamines by using DMSO as the methylthio or methylene source (Scheme e) 37. In the presence of NH 4 I, various aryl methyl thioethers and methylene‐bridged arylamines were synthesized in moderate to good yields.…”

Cyanomethylation and Cyclization of Aryl Alkynoates with Acetonitrile under Transition-Metal-Free Conditions: Synthesis of 3-Cyanomethylated Coumarins

“…By this strategy, a series of coumarin derivatives, a class of very important heterocyclic compounds in pharmaceuticals as well as in fluorescent materials, were synthesized via the addition of several radicals to aryl alkynoates, in which diselenides, Togni’s reagent (trifluoromethylation reagent), dialkyl H-phosphonates, sulfonylhydrazides, sulfinic acids, α-keto acids, ethyl bromo­difluoro­acetate, NIS, and 2,4-diones were employed as the radical sources. In continuation of our study on the covalent bond activation of inert solvents and their application in organic synthesis, in this work, we selected acetonitrile as the cyanomethyl source, through a peroxide promoted C–H bond activation and addition to the carbon–carbon triple bond of aryl alkynoates, followed by cyclization to synthesize 3-cyanomethylated coumarins.…”