Synlett 2017; 28(19): 2614-2618
DOI: 10.1055/s-0036-1590861
letter
© Georg Thieme Verlag Stuttgart · New York

Photochemistry of ortho-Azidocinnamoyl Derivatives: Facile and Modular Synthesis of 2-Acylated Indoles and 2-Substituted Quinolines under Solvent Control

S. Chaabounia, b, c, N. M. Pinkertona, S. Abidb, C. Galaupc, S. Chassaing*a
  • aInstitut des Technologies Avancées en Sciences du Vivant (ITAV), Université de Toulouse, CNRS, UPS, 1 place Pierre Potier, 31106 Toulouse Cedex 1, France   Email: stefan.chassaing@itav.fr
  • bLaboratoire de Chimie Appliquée: HGP, Université de Sfax, Faculté des Sciences, Sfax 3000, Tunisia
  • cLaboratoire de Synthèse et Physicochimie de Molécules d’Intérêt Biologique (SPCMIB), CNRS-UMR5068, Université Paul Sabatier-Toulouse III, 118 route de Narbonne, 31062 Toulouse Cedex 9, France
The authors gratefully acknowledge the CNRS and Université Paul Sabatier-Toulouse III for financial support. This work was supported by the Agence Nationale de Recherche (ANR-13-JS07-0003-01 CiTrON-Fluo) and the CNRS. S.C. thanks the Campus France Agency and the Université de Sfax for financial support, and N.M.P. thanks the Fondation RITC and the Fondation Toulouse Cancer Santé for a post-doctoral scholarship.
Further Information

Publication History

Received: 03 May 2017

Accepted after revision: 11 July 2017

Publication Date:
17 August 2017 (eFirst)

Abstract

The light-promoted potential of ortho-azidocinnamoyl compounds is evaluated for heterocycle synthesis. Depending on the nature of the solvent, 2-acylated indoles were obtained under aprotic conditions, whereas the use of a protic medium led to 2-substituted quinolines. The synthetic significance of this metal-free method is that, by simply changing the solvent, the reaction outcome can be directed towards different key heterocyclic scaffolds.

Supporting Information

 
  • References and Notes

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  • 15 Typical Procedure: In a quartz tube under argon were successively added ortho-azidocinnamoyl derivative 1ak and the appropriate solvent to give a concentration of 3.2 mM. The resulting mixture was then irradiated using either the LUMOS 43® (1.5 h stirring time with CH2Cl2 as solvent) or a conventional tungsten lamp [6 h stirring time with EtOH–H2O (1:1) as solvent], as light sources. After evaporation of the solvent, purification of the crude product by column chromatography, eluting with an appropriate cyclohexane–EtOAc mixture, furnished the desired photocyclized products 2ak or 3/4 in pure form.
  • 16 Analytical Data for 2,3-Diacetyl-6-N,N-dimethylamino-1H-indole (2k, Scheme [2]): Orange solid; mp 176–179 °C; Rf 0.40 (cyclohexane–EtOAc, 70:30). FTIR (ATR, neat): 3322, 2921, 1670 (C=O), 1311 cm–1. 1H NMR (300 MHz, CDCl3): δ = 9.30 (br s, 1 H, NH), 7.65 (d, J = 9.2 Hz, 1 H), 6.87 (dd, J = 2.3, 9.2 Hz, 1 H), 6.53 (d, J = 2.3 Hz, 1 H), 3.02 (s, 6 H), 2.76 (s, 3 H), 2.62 (s, 3 H). 13C NMR (75 MHz, CDCl3): δ = 197.8, 191.4, 150.0, 137.3, 132.4, 122.6, 122.1, 117.9, 112.2, 92.4, 40.8, 32.1, 28.7. MS (DCI, +): m/z (%) = 245 (100) [M + H]+. HRMS (DCI, +): m/z [M + H]+ calcd for C14H17N2O2: 245.1290; found: 245.1289.
  • 17 Analytical Data for 2-Methyl-3-acetyl-7-N,N-dimethylaminoquinoline (3k, Scheme [3]): Orange-red solid; mp 118–121 °C; Rf 0.23 (cyclohexane–EtOAc, 70:30). FTIR (ATR, neat): 2925, 1666 (C=O), 1616, 1511, 1422 cm–1. 1H NMR (300 MHz, CDCl3): δ = 8.34 (s, 1 H), 7.66 (d, J = 9.0 Hz, 1 H), 7.12 (dd, J = 2.5, 9.0 Hz, 1 H), 7.05 (d, J = 2.5 Hz, 1 H), 3.13 (s, 6 H), 2.88 (s, 3 H), 2.65 (s, 3 H). 13C NMR (75 MHz, CDCl3): δ = 198.9, 158.9, 152.9, 150.3, 138.7, 129.4, 126.4, 117.7, 115.6, 105.6, 40.3, 28.7, 26.2. MS (DCI, +): m/z (%) = 229 (100) [M + H]+. HRMS (DCI, +): m/z [M + H]+ calcd for C14H17N2O: 229.1341; found: 229.1347.