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Synlett 2010(19): 2899-2904  
DOI: 10.1055/s-0030-1259027
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

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

Wenying Bi, Xiliu Yun, Yanfeng Fan, Xiuxiang Qi, Yunfei Du*, Jianhui Huang*
Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, P. R. of China
Fax: +86(22)27404031; e-Mail: duyunfeier@tju.edu.cn; e-Mail: jhuang@tju.edu.cn;
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Publikationsverlauf

Received 5 September 2010
Publikationsdatum:
03. November 2010 (online)

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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.

Key words

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.