Concurrent α-Iodination and N-Arylation of Cyclic β-Enaminones

Abstract

A variety of N-substituted 3-aminocyclohex-2-enones were converted into the corresponding N-arylated α-iodo enaminones in high yields via concurrent α-iodination and N-arylation mediated by ArI(OAc)₂. A mechanism is postulated to account for the reaction differences between the cyclic and the acyclic β-enamin­ones, which undergo predominant α-acetoxylation under the same reaction conditions.

Key words

polyvalent iodine compounds - α-iodination - PIDA - α-iodo enaminones - 3-aminocyclohex-2-enones

References and Notes

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• 8a

  CaH₂-dried EtOAc, THF, MeCN, and CH₂Cl₂ were also tested as solvents, but were not superior to DCE.

• 8b

  The conversion was very slow at 40 ˚C.

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3

Compound 3a
Crystallized in the monoclinic space group P2 (1)/c with cell dimensions: a = 10.497 (2) Å, b = 13.607 (3) Å, c = 11.987 (2) Å, α = 90˚, β = 114.36 (3)˚, γ = 90˚, V = 1559.9 (5) Å^³, D _c  = 1.657 g/cm^³, Z = 4. CCDC: 753753.

14

General Procedure for α-Iodination and N-Arylation of β-Enaminones
To a solution of substrate 1 (1.0 mmol) in dried DCE (10 mL) was added dropwise a solution of aryliodine diacetate 2 (1.3 mmol) in dried DCE (10 mL) at 60 ˚C under nitrogen atmosphere. After the addition, the reaction mixture was stirred at this temperature until the conversion was complete as indicated by TLC. Then the mixture was cooled to r.t., treated with sat. aq NaHCO₃ (40 mL) and extracted with CH₂Cl₂ (3 × 20 mL). The combined organic layer was dried over Na₂SO₄ and evaporated under reduced pressure to remove the solvent. The residue was purified by column chromatography using a mixture of PE and EtOAc as eluent to afford the product.
Compound 3a: yellow solid, mp 106-108 ˚C. ^¹H NMR (500 MHz, CDCl₃): δ = 7.32 (t, J = 7.9 Hz, 4 H), 7.14 (t, J = 7.4 Hz, 2 H), 7.02 (d, J = 7.7 Hz, 4 H), 2.75-2.65 (m, 2 H), 2.58 (t, J = 6.0 Hz, 2 H), 2.04-1.91 (m, 2 H). ^¹³C NMR (100 MHz, CDCl₃): δ = 193.09, 166.95, 145.20, 129.52, 125.45, 125.22, 95.80, 37.54, 34.04, 21.38. ESI-LRMS: m/z = 390.2 [M + H⁺].
Compound 5a: yellow solid, mp 102-104 ˚C. ^¹H NMR (400 MHz, DMSO): δ = 7.51 (dd, J = 4.8, 2.5 Hz, 3 H), 7.35 (dd, J = 7.7, 1.9 Hz, 2 H), 2.43 (s, 3 H), 2.35 (s, 3 H), 2.22 (s, 3 H). ESI-LRMS: m/z = 271.9 [M + K⁺]. The spectroscopic data for all the new compounds could be found in the Supporting Information.