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Synlett 2009(3): 411-416  
DOI: 10.1055/s-0028-1087533
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

The Baylis-Hillman Bromides as Versatile Synthons: A Facile One-Pot Synthesis of Indolizine and Benzofused Indolizine Frameworks

Deevi Basavaiah*, Badugu Devendar, Dandamudi V. Lenin, Tummanapalli Satyanarayana
School of Chemistry, University of Hyderabad, Hyderabad 500 046, India
Fax: +91(40)23012460; e-Mail: dbsc@uohyd.ernet.in;
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Publication History

Received 8 October 2008
Publication Date:
21 January 2009 (online)

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Abstract

A facile one-pot synthesis of indolizine, benzofused indolizines {pyrrolo[1,2-a]quinoline and pyrrolo[1,2-a]isoquinoline} derivatives from the Baylis-Hillman (B-H) bromides, via an interesting strategy involving 1,5-cyclization of nitrogen ylides has been described.

Key words

Baylis-Hillman bromides - 1,5-cyclization strategy - indolizines - benzofused indolizines - quinoline - isoquinoline

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1-Aza-8-cyano-7-phenylbicyclo[4.3.0]nona-2,4,6,8-tetraene (2a) - Representative Procedure
To 2-(bromomethyl)-3-phenylprop-2-enenitrile [¹0] (1 mmol, 0.222 g) pyridine (3 mL) was added and stirred for 15 min (formation of pyridinium salt was observed as shown by TLC) at r.t. The reaction mixture was diluted with DMF (3 mL) and K2CO3 (5 mmol, 0.690 g) was added. The reaction mixture was then heated at 80 ˚C for 3 h and was allowed to cool to r.t. Saturated aq NaCl soln (5 mL) was added and extracted with CH2Cl2 (5 × 10 mL). The combined organic layer was dried over anhyd Na2SO4. Solvent was evaporated, and the residue, thus obtained, was purified by column chromatography (SiO2, 5% EtOAc in hexanes) to furnish the pure compound 2a as a colorless solid. Yield 52% (0.114 g); mp 128-130 ˚C. ¹H NMR (400 MHz, CDCl3): δ = 6.60-6.70 (m, 1 H), 6.77-6.86 (m, 1 H), 7.32-7.40 (m, 1 H), 7.46-7.53 (m, 2 H), 7.56-7.68 (m, 3 H), 7.74 (s, 1 H), 7.88 (d, 1 H, J = 7.2 Hz). ¹³C NMR (100 MHz, CDCl3): δ = 96.94, 113.60, 116.22, 117.46, 118.16, 118.92, 120.05, 125.31, 127.15, 128.67, 129.00, 129.68, 132.56. IR (KBr): ν = 2222 cm-¹. LC-MS: m/z = 219 [M + H]+. Anal. Calcd for C15H10N2: C, 82.55; H, 4.62; N, 12.84. Found: C, 82.51; H, 4.65; N, 12.70.

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Detailed X-ray crystallographic data are available from the CCDC, 12 Union road, Cambridge CB2 1EZ, UK; for compounds 2a (CCDC # 693505), 3a (CCDC # 693506), 4a (CCDC # 693507).

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1-Aza-12-cyano-11-phenyltricyclo[8.3.0.0 ²,7 ]trideca-2,4,-6,8,10,12-hexaene (3a) - Representative Procedure
To a stirred solution of 2-(bromomethyl)-3-phenylprop-2-enenitrile (1 mmol, 0.222 g) in DMF (3 mL) was added quinoline (2 mmol, 0.258 g) at r.t. After stirring for 1 h (salt formation was observed as evidenced by TLC), K2CO3 (5 mmol, 0.690 g) was added and heated for 5 h at 80 ˚C. The reaction mixture was allowed to cool to r.t. and diluted with sat. aq NaCl soln (5 mL) and extracted with CH2Cl2 (5 × 10 mL). The combined organic layers were dried over anhyd Na2SO4. Solvent was evaporated, and the residue, thus obtained, was purified by column chromatography (SiO2, 8% EtOAc in hexanes) to furnish the pure compound 3a as a colorless solid. Yield 45% (0.120 g); mp 160-162 ˚C. ¹H NMR (400 MHz, CDCl3): δ = 7.11 (d, 1 H, J = 9.6 Hz), 7.34-7.68 (m, 9 H), 7.85 (d, 1 H, J = 8.4 Hz), 8.26 (s, 1 H). ¹³C NMR (100 MHz, CDCl3): δ = 96.68, 114.43, 116.19, 117.35, 118.04, 120.39, 122.03, 124.52, 125.64, 127.50, 128.10, 128.84, 128.92, 129.00, 129.05, 132.28, 132.38.
IR (KBr): ν = 2226 cm-¹. LC-MS: m/z = 269 [M + H]+. Anal. Calcd for C19H12N2: C, 85.05; H, 4.51; N, 10.44. Found: C, 85.11; H, 4.54; N, 10.57.

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The single crystal X-ray structure revealed the presence of two molecules in the asymmetric unit. For clarity we have shown one molecule in the ORTEP diagram.