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Synlett 2009(19): 3127-3130  
DOI: 10.1055/s-0029-1218298
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Palladium-Mediated Reductive Heck Cyclization for the Formation of Dibenzoazepinone Framework

K. C. Majumdar*a, Santanu Chakravortya, Tapas Ghosha, B. Sridharb
a Department of Chemistry, University of Kalyani, Kalyani 741235, West Bengal, India
e-Mail: kcm_ku@yahoo.co.in;
b Laboratory of X-ray Crystallography, IICT, Hyderabad 500007, India
Further Information

Publication History

Received 15 September 2009
Publication Date:
15 October 2009 (online)

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Abstract

The dibenzoazepinone framework has been synthesized through a palladium-mediated Sonogashira cross-coupling followed by a reductive Heck cyclization. The reactions are simple, straightforward, and have been carried out under ligand-free conditions.

Key words

dibenzoazepinone - reductive Heck - Sonogashira cross coupling - Pd(PPh3)4

    References and Notes

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9

CCDC 747690 contains supplementary crystallographic data for the structure 4f.

10

General Procedure for the Formation of Amide 3f
A mixture of 2-iodobenzoic acid¹² (500 mg, 2.01 mmol) and SOCl2 was stirred at 100 ˚C for 3 h. After evaporation of the solvent, the residue was dissolved in CH2Cl2 (20 mL). A solution of amine 2f (583 mg, 2.01 mmol) in CH2Cl2 (20 mL) and TBAHS (cat. amount) was added to the stirred solution of acid chloride. To this reaction mixture an aq solution of K2CO3 (556 mg, 4.03 mmol) was added slowly. After stirring for 5 h at r.t., the solution was washed with 5% HCl (2 × 20 mL) and then with 5% aq NaOH (2 × 20 mL). The organic layer was dried (Na2SO4) and the solvent evaporated under reduced pressure. The residue was purified by column chromatography over silica gel using PE-EtOAc (7:3) as an eluent.
Compound 3f: white solid, yield 78%, mp 176-178 ˚C. IR (KBr): νmax = 2212, 1738, 1651, 1565 cm-¹. ¹H NMR (400 MHz, CDCl3): δ = 1.08 (t, 3 H, J = 7.2 Hz), 3.56-3.68 (m, 1 H), 4.49-4.61 (m, 1 H), 6.48 (d, 1 H, J = 9.6 Hz), 6.82-6.83 (m, 1 H), 7.03-7.11 (m, 1 H), 7.21-7.26 (m, 2 H), 7.45-7.47 (m, 3 H), 7.56-7.70 (m, 4 H), 8.15 (d, 1 H, J = 9.6 Hz). ¹³C NMR (100 MHz, CDCl3): δ = 12.8, 43.7, 82.1, 93.6, 117.0, 117.6, 121.5, 126.7, 127.0, 127.6, 128.7, 128.8, 129.9, 130.1, 131.7, 131.9, 132.6, 139.8, 141.3, 141.9, 153.0, 159.6, 169.7. HRMS: m/z found for C26H18INO3: 542.1890 [M+ + Na]. Anal. Calcd for C26H18INO3: C, 60.13; H, 3.49; N, 2.70. Found: C, 60.33; H, 3.29; N, 2.93.

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General Procedure for Reductive Heck Cyclization of Compound 3f A mixture of compound 3f ¹² (100 mg, 0.19 mmol), HCOONa (19.6 mg, 0.29 mmol), Pd(PPh3)4 (6.6 mg,
5.710-³ mmol) in DMF-H2O (10 mL, 7:3) was heated with continuous stirring at 120 ˚C for 4.2 h. After completion of the reaction as monitored by TLC, the reaction mixture was cooled and H2O (5 ml) was added. This was then extracted with CH2Cl2 (3 × 10 mL). The CH2Cl2 extract was washed with H2O (3 × 10 mL) followed by brine (10 mL). The organic layer was dried (Na2SO4). Evaporation of CH2Cl2 furnished a crude mass, which was purified by column chromatography over silica gel. Elution of the column with PE-EtOAc (3:1) afforded product 4f.
Compound 4f: white solid, yield 85%, mp 198-200 ˚C. IR (KBr): νmax = 1724, 1633 cm-¹. ¹H NMR (400 MHz, CDCl3): δ = 1.19-1.27 (m, 3 H), 3.74-3.81 (m, 1 H), 4.69-4.76 (m, 1 H), 6.18 (d, 1 H, J = 9.8 Hz), 6.98 (s, 1 H), 7.08-7.09 (m, 2 H), 7.19-7.20 (m, 3 H), 7.28-7.31 (m, 2 H), 7.38-7.41 (m, 1 H), 7.45-7.49 (m, 1 H), 7.57 (d, 1 H, J = 9.0 Hz), 7.63 (d, 1 H, J = 9.8 Hz), 7.89 (dd, 1 H, J = 0.8, 7.6 Hz). ¹³C NMR (100 MHz, CDCl3): δ = 13.9, 44.3, 114.3, 116.9, 117.3, 124.9, 127.8, 128.4, 128.5, 128.8, 128.9, 130.9, 131.7, 131.9, 132.2, 132.4, 132.8, 134.6, 135.4, 136.4, 140.5, 145.04, 152.2, 159.9, 167.6. HRMS: m/z calcd for C26H19NO3: 394.1438 [M+ + H]; found: 394.1406 [M+ + H]. Anal. Calcd for C26H19NO3: C, 79.37; H, 4.87; N, 3.56. Found: C, 79.58; H, 5.04; N, 3.75.

12

2-Bromobenzoic acid can also be used to give the corrosponding 2-bromo derivative 3 which also undergoes reductive Heck cyclization to afford 4f (yield 80%).