Copper‐Promoted Tandem Radical Reaction of 2‐Oxindoles with Formamides: Facile Synthesis of Unsymmetrical Urea Derivatives

Abstract

Ac onvenient copper-promoted tandemr adical reaction of 2-oxindoles with formamidesp roducing unsymmetrical urea derivatives is described. This radicalmediated reaction enables the formation of one C=Oa nd one CÀNb ond through ad omino CÀOc oupling, ring cleavage and CÀNc oupling process,w hich features a broad substrate scope and excellent selectivity.I na ddition, tBuOOH not only acts as the oxidant, but also as the oxygen source.T he proposed reactionm echanism is supported by control experiments.

Nickel Catalyzed Alkylation of Oxindoles with Alkyl Alcohols

“…Cleavage of γ ‐lactam ring to urea : [27] To a Schlenk tube were added 3‐ethylindolin‐2‐one 39 (0.5 mmol), DMF (0.9 mL), Cu(OAc) 2 (0.12 mmol), and t BuOOH (2.2 mmol). The Schlenk tube was stirred at 100 °C under air for 1 h until complete conversion of 39 .…”

“…1 H NMR (500 MHz, CDCl 3 ): δ = 8.16 (s, 1H), 7.10-7.02 (m, 2H), 6.87 (td, J = 7.6, 1.0 Hz, 1H), 6.72 (d, J = 7.7 Hz, 1H), 3.30 (t, J = 6.0 Hz, 1H), 1.87-1.76 (m, 2H), 1.61-1.55 (m, 3H), 1.43-1.37 (m, 2H), 1.32 (, 2H), 1. 27…”

“…1,1-dimethyl-3-(2-propionylphenyl)urea (39-a): [27] Following the general procedure G, the title product was obtained as a dark yellow solid using silica-gel column chromatography eluting with 15 % ethyl acetate in hexane (Yield: 64 %, 35.2 mg). 1 H NMR (500 MHz, CDCl 3 ): δ = 11.44 (s, 1H), 8.62 (dd, J = 8.6, 1.1 Hz, 1H), 7.87 (dd, J = 8.1, 1.6 Hz, 1H), 7.46-7.50 (ddd, J = 8.8, 7.2, 1.6 Hz, 1H), 6.96 (ddd, J = 8.1, 7.2, 1.2 Hz, 1H), 3.08 (s, 6H), 3.04 (t, J = 7.2 Hz, 2H), 1.21-1.18 ppm (t, J = 7.2 Hz, 3H).…”

Recent Uses of N,N-Dimethylformamide and N,N-Dimethylacetamide as Reagents

“…At 100 °C in DMF, Cu catalyst associated to t -BuOOH led to unsymmetrical ureas from 2-oxindoles (Equation (65)) [ 76 ]. The peroxide would mediate the cleavage reaction, and was the oxygen source of the benzylic carbonyl.…”

Ir-Catalyzed C–H Amidation Using Carbamoyl Azides for the Syntheses of Unsymmetrical Ureas

“…Recently, many groups have reported a synthetic method for urea using transition metals (Scheme a). − Specifically, Cu catalysts have been employed for formamide-type reactions with radical initiators, while the Pd employs isocyanate intermediates, and the iron- or ruthenium-catalyzed preparation of unsymmetrical urea requires methanol as a carbonyl source for double C–N bond formation. However, these methodologies require harsh conditions for efficient transformations and purification.…”