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Synlett 2011(4): 517-520  
DOI: 10.1055/s-0030-1259547
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Electrophilic Cyclization of Buta-1,3-diynylarenes: Synthesis of Precursors of (Z)-3-Ene-1,5-diyne Systems Fused to Heterocycles

Natalia A. Danilkinaa, Stefan Bräse*b, Irina A. Balova*a
a Saint-Petersburg State University, Department of Organic Chemistry, Universitetskiy pr. 26, 198504, Saint-Petersburg, Russian Federation
Fax: +7(812)4286939; e-Mail: irinabalova@yandex.ru;
b Karlsruhe Institute of Technology, Campus South, Institute of Organic Chemistry, Fritz-Haber-Weg 6, 76131 Karlsruhe, Germany
Fax: +49(721)6088581; e-Mail: braese@kit.edu;
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Publication History

Received 9 November 2010
Publication Date:
11 February 2011 (online)

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Abstract

A simple, convenient, and promising strategy for the synthesis of 2-ethynyl-3-iodo-benzothiophenes, -benzofurans, and -indoles based on electrophilic cyclization of easily available ortho-functionalized (buta-1,3-diynyl)arenes was developed. The unique potential of using these compounds as starting materials for the synthesis of enediyne systems, containing thiophene, furan, and pyrrole units is demonstrated.

Key words

electrophilic cyclization - alkynes - heterocycles - enediynes

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Relative molar ratio of 2d and 2d′ was determined by ¹H NMR analysis of the integral intensity of the signals of acetylene hydrogen atom (δ = 3.74 ppm) of 2d′, TMS group (δ = 0.32 ppm) of 2d and multiplet signals of aromatic hydrogen atoms (δ = 7.38-7.50 and 7.67-7.76 ppm) of 2d and 2d′ (CDCl3, 400 MHz, TMS as reference).

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It was determined by TLC that O-benzyl-2-(dodeca-1,3-diynyl)phenol reacts with ICl in MeCN in similar way giving benzofuran 3i with iodochlorinated triple bond.

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General Procedure for Electrophilic Cyclization of ortho -Buta-1,3-diynylthiophenol, -Aniline, and -Phenol Derivatives Using I 2 To an Ar flushed solution of corresponding o-(buta-1,3-diynyl)arene 1 (0.2 mmol) in MeCN (3 mL), a solution of iodine (0.2 mmol, 0.051 g,) in MeCN (2 mL) was added dropwise. The reaction mixture was stirred at corresponding temperature up to disappearance of starting material according to TLC monitoring (see Table  [¹] ). Then, the reaction mixture was diluted with 5% aq solution of Na2S2O3 and extracted with CH2Cl2 (3 × 7 mL). The combined organic layers were washed with H2O, dried over anhyd Na2SO4, and concentrated under reduced pressure to yield the crude product, which was purified by column chromatography on silica gel using pentane (for 2a,b,d,e,g) or cyclohexane-EtOAc (2c,f) as the eluent.

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Selected Data for 2c
Mp 73-75 ˚C. IR (neat): ν = 3124 (OH), 2927 (CH), 2222 (CºC), 1449, 1427, 1370, 1326, 1294, 1243, 1192, 1158, 1062, 1031, 1016, 983, 938, 914, 849, 831, 747, 721, 707 cm-¹. ¹H NMR (400 MHz, CDCl3): δ = 2.01 (t, J = 6.5 Hz, 1 H), 2.83 (t, J = 6.1 Hz, 2 H), 3.88-3.93 (m, 2 H), 7.38-7.46 (m, 2 H), 7.67-7.72 (m, 2 H). ¹³C NMR (100 MHz, CDCl3): δ = 24.4, 60.8, 87.6, 96.9, 122.1, 125.0, 125.7, 126.1, 126.4, 138.6, 140.3 (two signals are overlapping with each other). MS (EI, 70 eV): m/z (%) = 328.0(100) [M]+, 296.9 (66)
[M - CH2OH]+, 171.0(31), 139.1 (5) 126.1 (14). HRMS: m/z calcd for C12H9OSI: 327.9419. Found: 327.9418. Anal. Calcd for C12H9OSI: C, 43.92; H, 2.76; S, 9.77. Found: C, 43.85; H, 2.69; S, 9.61.

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General Procedure for the Synthesis of Enediyne Systems 4
To a stirred solution of 2-ethynyl-3-iodo heterocyle 2 (0.1 mmol) in DMF (2 mL), the alkyne (0.2 mmol), Pd(PPh3)4 (5 mol%), Ph3P (10 mol%), and DIPA (0.4 mmol) were added. The reaction vial was evacuated and flushed with Ar several times. After that 15 mol% of CuI was added, the reaction vial was then sealed and flushed with Ar. The reaction mixture was allowed to stir at 40-50 ˚C (see Table  [²] ) overnight. After cooling, the reaction mixture was poured into the sat. aq solution of NH4Cl and extracted with CH2Cl2 (3 × 10 mL). The combined organic layers were washed two times with H2O, dried over anhyd Na2SO4, and concentrated under reduced pressure to yield the crude product, which was purified by column chromatography on silica gel using pentane (for 4a,c,d,h,i) or cyclohexane-EtOAc (for 4b,e-g) as the eluent.

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Selected Data for 4f IR (film on KBr): ν = 3358 (OH), 3061 (CH), 2958 (CH), 2897 (CH), 2223 (CºC), 2149 (CºC), 1458, 1433, 1349, 1317, 1249, 1216, 1160, 1081, 1046, 976, 938, 896, 843, 729, 687, 642 cm-¹. ¹H NMR (400 MHz, CDCl3): δ = 0.32 (s, 9 H), 2.02 (t, J = 6.7 Hz, 1 H), 2.83 (t, J = 6.1 Hz, 2 H), 3.85-3.90 (m, 2 H), 7.38-7.45 (m, 2 H), 7.70-7.72 (m, 1 H), 7.83-7.85 (m, 1 H). ¹³C NMR (100 MHz, CDCl3): δ = 0.1, 24.5, 60.8, 75.8, 97.5, 97.7, 101.5, 122.0, 122.8, 123.3, 125.1, 126.1, 127.3, 138.0, 138.5. MS-FAB: m/z (%) = 299.1 (61) [M+ + H], 298.1 (100) [M+]. HRMS: m/z calcd for C17H18OSSi: 298.0848; found: 298.0845.