Synthesis of Imidazolidinone, Imidazolone, and Benzimidazolone Derivatives through Oxidation Using Copper and Air

Abstract

A new synthetic method of urea derivatives using copper and air was developed. These mild conditions provided moderate to very good yields for 15 examples (53-93%), while low yields were obtained with sterically hindered substrates (3 examples). The reaction was found to go through an in situ-generated copper-N-heterocyclic carbene, which is then oxidized into cyclic urea derivatives possessing alkyl, benzyl, aryl, hydroxy, Boc-protected, and tertiary amine groups. compounds will be disclosed in due course. ASSOCIATED CONTENT Supporting Information The Supporting Information is available free of charge on the ACS Publications website. Details of the synthetic procedures of the urea derivatives, imidazoliums, imidazoliniums, and benzimidazoliums and the copies of 1 H, 13 C, and 19 F NMR spectra for 1a-t and 2a-t could be found in the Supporting Information.

The key role of R–NHC coupling (R = C, H, heteroatom) and M–NHC bond cleavage in the evolution of M/NHC complexes and formation of catalytically active species

“…Oxidation of M/NHC complexes 51 , leading to formation of O–NHC bond and affording imidazoline-2-ones 52 or related substances, certainly deserves attention. 172 , 181 , 182 , 222 For example, homogeneous aerobic oxidation of Cu I /NHC complexes can be used for preparative synthesis of cyclic ureas ( Scheme 11 ). 181 The reaction is highly sensitive to the NHC steric bulkiness and possibly includes a reductive elimination step.…”

Reversal of Enantioselectivity in the Conjugate Addition Reaction of Cyclic Enones with the CuOTf/Azolium Catalytic System

“…These results strongly indicate that Y contains the same azolium cation (NHC•H + ) as 4b . Recently, Ollevier observed that treatment of a NHC•CuX complex with atmospheric air in CH 2 Cl 2 afforded the corresponding hydrolysis product such as an azolium compound [ 33 , 34 ].…”

TEMPO‐Mediated Synthesis of N‐(Fluoroalkyl)imidazolones via Reaction of Imidazoles with Iodofluoroacetate

“…These results suggest that this reaction pathway differs from previous methods involving an imidazolium salt. [6][7][8][9] The N-methyl benzimidazole 1 a did not furnish the required benzimidazolone in the absence of alkyl halide under standard conditions (Scheme 2, eq. 3).…”

“…In recent years, the oxidation of imidazolium salts using strong oxidants has proven to be an effective pathway to imidazolones (Scheme a) . Ollevier and colleagues recently demonstrated that imidazolidinone, imidazolone, and benzimidazolone derivatives could be synthesized efficiently via the oxidation of imidazolium salts using a copper catalyst and air as an oxidant at room temperature . However, this route requires the initial synthesis of imidazolium salts.…”

“…[5] Due to the medicinal importance of imidazolones, much effort has been devoted to their synthesis. [6][7][8][9][10][11][12] In recent years, the oxidation of imidazolium salts using strong oxidants has proven to be an effective pathway to imidazolones (Scheme 1a). [6][7][8][9] Ollevier and colleagues recently demonstrated that imidazolidinone, imidazolone, and benzimidazolone derivatives could be synthesized efficiently via the oxidation of imidazolium salts using a copper catalyst and air as an oxidant at room temperature.…”