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Synlett 2009(13): 2083-2088  
DOI: 10.1055/s-0029-1217702
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Synthesis of Heterocycle-Annulated Medium-Sized Oxacycles and Lactone Derivative by Intramoleculer Heck Reaction

K. C. Majumdar*, Rajendra Narayan De, Buddhadeb Chattopadhyay, B. Roy
Department of Chemistry, University of Kalyani, Kalyani 741235, West Bengal, India
e-Mail: kcm_ku@yahoo.co.in;
Further Information

Publication History

Received 20 April 2009
Publication Date:
16 July 2009 (online)

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Abstract

An efficient and convergent methodology for the highly strained medium-sized oxacyclic compounds and lactone derivatives has been developed via palladium-catalyzed intramoleculer Heck reaction.

Key words

intramoleculer Heck reaction - palladium acetate - 8-exo-trig - eight-membered oxacycle - lactone

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18

General Procedure for the Synthesis of the Compound by Heck Reaction A mixture of 3a (70 mg, 0.182 mmol), TBAB (147 mg, 0.455 mmol), and dry KOAc (26 mg, 0.265 mmol) was taken in dry DMF (10 mL). Pd(OAc)2 (10 mol%, 4.1 mg) was added, and the mixture was stirred on an oil bath at 110 ˚C for ca. 2 h. The reaction mixture was cooled, DMF was removed under reduced pressure, H2O (3 mL) was added and extracted with EtOAc (3 × 20 mL) and washed with H2O (2 × 20 mL), followed by brine (20 mL). The organic layer was dried (Na2SO4), and the solvent was distilled off to furnish a viscous mass which was purified by column chromatography over silica gel. Elution of the column with 20% EtOAc-hexane afforded the product 8a. Similarly, other compounds were synthesized.
Compound 8a: white solid, mp 174 ˚C. IR (KBr): 2918, 2899, 1643, 1600 cm-¹ . ¹H NMR (400 MHz, CDCl3): δ = 3.66 (s, 3 H, NCH3), 4.02 (s, 2 H,=CCH2), 5.17 (s, 1 H, =CHa), 5.42 (s, 1 H, =CHb), 5.48 (s, 2 H, OCH2), 7.12-7.19 (m, 4 H, ArH), 7.20 (t, 1 H, J = 7.88 Hz, ArH), 7.25 (d, 1 H, J = 5.2 Hz, ArH), 7.43 (t, 1 H, J = 7.80 Hz, ArH), 7.65 (d, 1 H, J = 7.96 Hz, ArH). ¹³C NMR (75 MHz, CDCl3): δ = 29.67, 36.98, 73.86, 114.17, 114.26, 120.53, 122.31, 123.83, 127.86, 128.37, 128.45, 128.65, 128.69, 133.47, 133.93, 137.01, 141.33, 143.94, 148.03, 159.00. MS (TOF MS ES+): m/z = 326.13 [M + Na+]. Anal. Calcd (%) for C20H17NO2: C, 79.19; H, 5.65; N, 4.62. Found: C, 79.29; H, 5.77; N, 4.57.

22

The spectral data, especially NMR studies, showed that the OCH2 protons appears as two separate singlets which is further supported by the DEPT experiment. DEPT contains two extra methylene groups due to the rapid interconversion of the existing possible conformers.
Compound 10b: yellow solid, mp 250 ˚C. IR (KBr): 2941, 2838, 1647, 1625 cm-¹ . ¹H NMR (300 MHz, CDCl3): δ = 3.45-3.61 (m, 2 H, =CHCH 2), 3.80 (s, 3 H, OCH3), 4.89 (s, 1 H, OCHa), 5.44 (s, 1 H, OCHb), 6.74 (d, 1 H, J = 11.4 Hz, =CHa), 7.11-7.15 (m, 1 H, =CHb), 7.19-7.22 (m, 5 H, ArH), 7.43-7.54 (m, 4 H, ArH), 8.23 (d, 1 H, J = 7.5 Hz, ArH), 8.46 (d, 1 H, J = 3.2 Hz, ArH). ¹³C NMR (75 MHz, CDCl3): δ = 31.6, 59.4, 109.2, 112.6, 112.7, 115.1, 119.2, 125.3, 125.8, 128.5, 128.9, 129.5, 136.0, 136.7, 138.8, 138.3, 154.1, 154.7, 159.8, 172.5, 194.6. (TOF MS ES+):
m/z = 419.08 [M + Na]. Anal. Calcd (%) for C25H20N2O3: C, 75.74; H, 5.08; N, 7.07. Found: C, 75.81; H, 5.03; N, 7.21.