Copper-Mediated N-Arylations of Hydantoins

Abstract

A set of two broadly applicable procedures for the N-arylation of hydantoins is reported. The first one relies on the use of stoichiometric copper(I) oxide under ligandand base-free conditions and enables a clean regioselective arylation at the N 3 nitrogen atom, while the second one is based on the use of catalytic copper(I) iodide and trans-N,N′-dimethylcyclohexane-1,2-diamine and promotes arylation at the N 1 nitrogen atom. Importantly, the combination of these two procedures affords a straightforward entry to diarylated hydantoins.

N1‐ and N3‐Arylations of Hydantoins Employing Diaryliodonium Salts via Copper(I) Catalysis at Room Temperature

“…The reaction was stirred for 24 h. The reaction mixture was purified by column chromatography (AcOEt/Hexane: 5/95 followed by 20/70) to afford 4 g (46 mg, 0.177 mmol, 71 %) as a brownish solid. ([1,1'-biphenyl]-4-yl)-5,5-dimethylimidazolidine-2,4-dione (4 i) [14] Synthesized following general procedure A starting from 5,5dimethylhydantoin (1 a) (32 mg, 0.25 mmol) and (biphenyl)(2,4,6trimethylphenyl)iodonium triflate (2 h) (164 mg, 0.30 mmol). The reaction was stirred for 16 h. The reaction mixture was purified by column chromatography (AcOEt/Hexane: 10/90 followed by 30/70) to afford 4 i (58 mg, 0.205 mmol, 82 %) as a white solid.…”

“…Synthesized following general procedure B starting from 5,5-dimethyl-3-(4-nitrophenyl)hydantoin (4 e) (62 mg, 0.25 mmol) and bis(4-methylphenyl)iodonium triflate (2 c) (138 mg, 0.30 mmol). The reaction was stirred for 10 h. The reaction mixture was purified by column chromatography (AcOEt/Hexane: 5/95 followed by 30/70) to afford 5-dimethyl-2,4-dioxo-3-phenylimidazolidin-1-yl)benzonitrile (5 i) [14] Synthesized following general procedure B starting from 3phenyl-5,5-dimethylhydantoin (4 a) (51 mg, 0. 5-isopropyl-3-phenylimidazolidine-2,4-dione (3 d) (S)-5-isopropylimidazolidine-2,4-dione (1 e) (284 mg, 2 mmol) and diphenyliodonium triflate (2 a) (1.032 g, 2.4 mmol), CuI (38 mg, 0.2 mmol) and K 3 PO 4 (424 mg, 2 mmol) were added under N 2 atmosphere to a dried 50 mL round-flask.…”

“…Thereafter, triarylbismuthane, [12] aryl boronic acid, [12] and aryl iodide [13] were also employed as aryl partners in Cu‐mediated protocols (Scheme 1b). Recently, Petit's group re‐established the Cu‐mediated N 3 ‐arylation and subsequently Cu‐catalysed N 1 ‐arylation of N 3 ‐aryl hydantoins using aryl halides (Scheme 1c) [14] . Although the method highlighted broad substrate scopes, ortho ‐substituted aryl groups failed to tolerate the reaction condition.…”

“…Recently, Petit's group re-established the Cu-mediated N 3 -arylation and subsequently Cu-catalysed N 1 -arylation of N 3 -aryl hydantoins using aryl halides (Scheme 1c). [14] Although the method highlighted broad substrate scopes, ortho-substituted aryl groups failed to tolerate the reaction condition. Also, N 3 -arylation of hydantoins containing both acidic C 5 À H and N 1 À H exhibited poor selectivity and hence limited hydantoins were studied.…”

2-Imidazolidinone benzofurans as unexpected outcome of the Lewis acid mediated Nenitzescu reaction

“…[25][26][27][28][29] Substituted 2-imidazolidinones have been exploited as chiral auxiliaries in asymmetric synthesis. 30 In literature, synthesis and properties of these structures and the structurally related hydantoins or 2-oxazolidone benzofurans include Cu(I)catalysed amidation of 2-bromobenzofuran 31,32 and an intramolecular addition of o-anisole substituted ynamides either transition metal-catalysed 33 or with the addition of an electrophilic iodine species. 34,35 These ynamides could be formed in situ with transition metals.…”