Syntheses of N-Alkylated Carbazolones via Pd(OAc)₂-Mediated Intramolecular Coupling of N-Substituted 3-(Arylamino)cyclohex-2-enones

Abstract

A variety of functionalized N-alkylated carbazolones were prepared via N-alkylation of 3-(arylamino)cyclohex-2-enones followed by an intramolecular oxidative coupling mediated by Pd(OAc)₂ under an oxygen atmosphere. This approach adopts an inverted sequence, consisting of the conventional annulation and subsequent N-alkylation.

N-substituted 3-(arylamino)cyclohex-2-enones - N-alkylated carbazolones - Pd(OAc)₂ - oxygen - CH activation

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10

General Procedure for the Synthesis of N-Substituted Carbazolones 3
To a solution of N-substituted 3-(arylamino)cyclohex-
2-enones 2a-n (1 mmol) in AcOH (15 mL) was added Pd(OAc)₂ (0.1 mmol), and the resulting solution was heated at 100 ˚C and passed through oxygen flow (1.0 L/min).
TLC was used to monitor the reaction progress. After the consumption of starting material, the reaction mixture was extracted by EtOAc (3 × 15 mL). The organic phase was combined, dried (anhyd Na₂SO₄). After filtration, the solvent was removed under reduced pressure to give the crude product. The residue was purified by flash column chromatography (EtOAc-PE, 1:3) on silica gel to give the desired products 3a-n. Compound 3a:^¹¹ white solid; mp 195-196 ˚C. ^¹H NMR (400 MHz, CDCl₃): δ = 8.27-8.23 (m, 1 H, ArH), 7.33-7.27 (m, 3 H, ArH), 3.72 (s, 3 H, NCH₃), 2.95 (t, J = 6.0 Hz, 2 H, COCH₂), 2.62 (t, J = 6.0 Hz, 2 H, CH₂), 2.30-2.23 (m, 2 H, CH₂). ESI-LRMS: m/z calcd for C₁₃H₁₃NO⁺: 200.1 [M + H⁺]; found: 200.1 [M + H⁺], 222 [M + Na⁺].
Compound 3b: brown solid; mp 230-231 ˚C. ^¹H NMR (400 MHz, CDCl₃): δ = 8.38 (d, J = 2.0 Hz, 1 H, ArH), 7.34 (dd, J = 9.0, 2.0 Hz, 1 H, ArH), 7.18 (d, J = 9.0 Hz, 1 H, ArH), 3.68 (s, 3 H, NCH₃), 2.92 (t, J = 6.0 Hz, 2 H, COCH₂), 2.56 (t, J = 6.0 Hz, 2 H, CH₂), 2.28-2.22 (m, 2 H, CH₂). ^¹³C NMR (100 MHz, CDCl₃): δ = 193.8, 153.0, 137.6, 134.9, 127.2, 125.8, 124.4, 111.8, 110.8, 37.7, 35.6, 23.1, 21.9. ESI-LRMS: m/z calcd for C₁₃H₁₂ ⁷⁹BrNO⁺: 280.0 [M + H⁺]; found: 280.0. The spectroscopic data for all the new compounds can be found in the Supporting Information.

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