Synlett 2006(3): 0466-0468  
DOI: 10.1055/s-2006-926238
LETTER
© Georg Thieme Verlag Stuttgart · New York

Stereoselective Synthesis of Tricyclic Pyranoxepin Derivatives by Ruthenium-Catalyzed Enyne Metathesis/Diels-Alder Reaction

K. C. Majumdar*, H. Rahaman, S. Muhuri, B. Roy
Department of Chemistry, University of Kalyani, Kalyani 741235, West Bengal, India
Fax: +91(33)25828282; e-Mail: kcm_ku@yahoo.co.in;
Further Information

Publication History

Received 26 August 2005
Publication Date:
06 February 2006 (online)

Abstract

Synthesis of tricyclic oxepin-annulated pyrone derivatives has been achieved by the ring-closing enyne metathesis using the first-generation Grubbs’ catalyst under a nitrogen atmosphere. The Diels-Alder reaction of these cyclized products with the dienophile proceeded smoothly to afford the tricyclic compounds in ­excellent yield.

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Typical Procedure for the Enyne RCM.
To a solution of substrate 4d (68.9 mg, 0.2 mmol) in dry degassed CH2Cl2 (8 mL) under N2 was added catalyst A (15 mg) and the reaction was stirred at r.t. for 8 h. After the removal of the solvent, the residue was purified by flash column chromatography on silica gel (PE-EtOAc, 4:1) to give 5d in 90% yield. Compound 5a: yield 82%; sticky liquid. IR (neat): νmax = 1704, 1665, 1568 cm-1. 1H NMR (400 MHz, CDCl3): δ = 2.13 (s, 3 H), 3.47 (d, J = 6.55 Hz, 2 H), 4.99 (s, 2 H), 5.09 (d, J = 10.8 Hz, 1 H), 5.25 (d, J = 17.5 Hz, 1 H), 5.60 (s, 1 H), 6.24 (t, J = 6.55 Hz, 1 H), 6.29 (dd, J = 17.5 Hz, J = 10.8 Hz, 1 H). MS: m/z = 204 [M+]. Anal. Calcd for C12H12O3: C, 70.59; H, 5.88. Found: C, 70.73; H, 5.72%.
Compound 5d: yield 90%; light-yellow solid, mp 112 °C. IR (KBr): νmax = 1698, 1658, 1568, 1491 cm-1. 1H NMR (400 MHz, CDCl3): δ = 2.13 (s, 3 H), 3.51 (d, J = 6.64 Hz, 2 H), 4.66 (s, 2 H), 5.07 (s, 2 H), 5.38 (s, 1 H), 5.41 (s, 1 H), 5.60 (s, 1 H), 6.39 (t, J = 6.64 Hz, 1 H), 6.82 (d, J = 8.88 Hz, 1 H), 7.21 (d, J = 8.88 Hz, 2 H). MS: m/z = 344, 346 [M+]. Anal. Calcd for C19H17O4Cl: C, 66.18; H, 4.93. Found: C, 65.98; H, 5.17%.

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Procedure for the Diels-Alder Reactions. A solution of 5d (17.2 mg, 0.05 mmol) and dimethylfumarate (14.4 mg, 0.1 mmol) in toluene was heated at 100 °C for 4 h. After removal of the solvent the residue was purified by flash column chromatography on silica gel (PE-EtOAc, 3:1) to give 6d in 95% yield. Compound 6d: yield 95%; white solid, mp 118-119 °C. IR (KBr): νmax = 1736, 1703, 1655, 1580 cm-1. 1H NMR (400 MHz, CDCl3): δ = 2.15 (s, 3 H), 2.44-2.48 (m, 1 H), 2.58-2.69 (m, 3 H), 2.95-3.05 (m, 3 H), 3.67 (s, 3 H), 3.76 (s, 3 H), 4.39 (d, J = 11.2 Hz, 1 H), 4.47 (d, J = 11.2 Hz, 1 H), 4.79 (d, J = 13.6 Hz, 1 H), 5.04 (d, J = 13.6 Hz, 1 H), 5.65 (s, 1 H), 6.79 (d, J = 8.8 Hz, 2 H), 7.22 (d, J = 8.8 Hz, 2 H). 13C NMR (125 MHz, CDCl3): δ = 19.93, 27.11, 31.09, 41.86, 42.76, 47.74, 52.57, 52.69, 67.37, 69.49, 101.93, 102.54, 116.32, 126.79, 129.90, 130.79, 133.98, 157.35, 159.99, 166.12, 168.50, 174.01, 175.07. MS: m/z = 488, 490 [M+]. Anal. Calcd for C25H25O8Cl: C, 61.41; H, 5.12. Found: C, 61.68; H, 5.30%.
Compound 6e: yield 96%; white solid, mp 125 °C. IR (KBr): νmax = 1736, 1704, 1650, 1580 cm-1. 1H NMR (400 MHz, CDCl3): δ = 2.15 (s, 3 H), 2.41-2.47 (m, 1 H), 2.58-2.68 (m, 3 H), 2.93-3.02 (m, 3 H), 3.67 (s, 3 H), 3.76 (s, 3 H), 4.39 (d, J = 11.5 Hz, 1 H), 4.48 (d, J = 11.5 Hz, 1 H), 4.79 (d, J = 13.4 Hz, 1 H), 5.05 (d, J = 13.4 Hz, 1 H), 5.65 (s, 1 H), 6.78 (d, J = 8.6 Hz, 1 H), 7.21-7.25 (m, 2 H). MS: m/z = 522, 524, 526 [M+]. Anal. Calcd for C25H24O8Cl2: C, 57.36; H, 4.59. Found: C, 57.66; H, 4.44%.