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

Natalia A. Danilkina; Stefan Bräse; Irina A. Balova

doi:10.1055/s-0030-1259547

LETTER

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

Natalia A. Danilkina^a, 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;

Abstract

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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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References

References and Notes

<A NAME="RG33910ST-1A">1a</A> Larock RC. In Acetylene Chemistry Diederich F. Stang PJ. Tykwinski RR. Wiley-VCH; Weinheim: 2005. p.51-99

<A NAME="RG33910ST-1B">1b</A> Mehta S. Larock RC. J. Org. Chem. 2010, 75: 1652 ; and references cited therein

<A NAME="RG33910ST-1C">1c</A> Manarin F. Roehrs JA. Brandão R. Nogueira CW. Zeni G. Synthesis 2009, 4001

<A NAME="RG33910ST-1D">1d</A> Cho C.-H. Neuenswander B. Larock RC. J. Comb. Chem. 2010, 12: 278

<A NAME="RG33910ST-1E">1e</A> Worlikar SA. Neuenswander B. Lushington GH. Larock RC. J. Comb. Chem. 2009, 11: 875

<A NAME="RG33910ST-1F">1f</A> Cho C.-H. Neuenswander B. Lushington GH. Larock RC. J. Comb. Chem. 2009, 11: 900

<A NAME="RG33910ST-1G">1g</A> Manarin F. Roehrs JA. Gay RM. Brandao R. Menezes PH. Nogueira CW. Zeni G. J. Org. Chem. 2009, 74: 2153

<A NAME="RG33910ST-1H">1h</A> Mehta S. Waldo JP. Larock RC. J. Org. Chem. 2009, 74: 1141

<A NAME="RG33910ST-1I">1i</A> Cho C.-H. Neuenswander B. Lushington GH. Larock RC. J. Comb. Chem. 2008, 10: 941

<A NAME="RG33910ST-2A">2a</A> Yue D. Larock RC. J. Org. Chem. 2002, 67: 1905

<A NAME="RG33910ST-2B">2b</A> Flynn BL. Verdier-Pinard P. Hamel E. Org. Lett. 2001, 3: 651

<A NAME="RG33910ST-2C">2c</A> Yue D. Larock RC. Tetrahedron Lett. 2001, 42: 6011

<A NAME="RG33910ST-3A">3a</A> Arcadi A. Cacchi S. Fabrizi G. Marinelli F. Moro L. Synlett 1999, 1432

<A NAME="RG33910ST-3B">3b</A> Yue D. Yao T. Larock RC.
J. Org. Chem. 2005, 70: 10292

<A NAME="RG33910ST-3C">3c</A> Okitsu T. Nakazawa D. Taniguchi R. Wada A. Org. Lett. 2008, 10: 4967

<A NAME="RG33910ST-4A">4a</A> Barluenga J. Trincado M. Rubio E. Gonzalez JM. Angew. Chem. Int. Ed. 2003, 42: 2406

<A NAME="RG33910ST-4B">4b</A> Amjad M. Knight DW. Tetrahedron Lett. 2004, 45: 539

<A NAME="RG33910ST-4C">4c</A> Yue D. Larock RC. Org. Lett. 2004, 6: 1037

<A NAME="RG33910ST-4D">4d</A> Yue D. Yao T. Larock RC. J. Org. Chem. 2006, 71: 62

<A NAME="RG33910ST-5A">5a</A> Wei S. Coleman RS. Lowary TL. Org. Biomol. Chem. 2009, 7: 3709

<A NAME="RG33910ST-5B">5b</A> Santin EP. Khanwalkar H. Voegel J. Collette P. Mauvais P. Gronemeye H. de Lera AR. ChemMedChem 2009, 4: 780

<A NAME="RG33910ST-5C">5c</A> Yang L.-Y. Chang C.-F. Huang Y.-C. Lee Y.-J. Hu C.-C. Tseng T.-H. Synthesis 2009, 1175

<A NAME="RG33910ST-5D">5d</A> Bang HB. Han SY. Choi DH. Yang DM. Hwang JW. Lee HS. Jun J.-G. Synth. Commun. 2009, 39: 506

<A NAME="RG33910ST-6A">6a</A> Zhou Y. Liu W.-J. Ma Y. Wang H. Qi L. Cao Y. Wang J. Pei J. J. Am. Chem. Soc. 2007, 129: 12386

<A NAME="RG33910ST-6B">6b</A> Kobayashi T, and Hasegawa Y. inventors; US 2005258398.

<A NAME="RG33910ST-7">7</A> Barluenga J. Trincado M. Rubio E. Gonzalez JM. Angew. Chem. Int. Ed. 2003, 42: 2406

<A NAME="RG33910ST-8A">8a</A> Vinogradova OV. Sorokoumov VN. Vasylevsky SF. Balova IA. Tetrahedron Lett. 2007, 48: 4907

<A NAME="RG33910ST-8B">8b</A> Vinogradova OV. Sorokoumov VN. Balova IA. Tetrahedron Lett. 2009, 50: 6358

<A NAME="RG33910ST-9A">9a</A> Sahu B. Namboothiri INN. Persky R. Tetrahedron Lett. 2005, 46: 2593

<A NAME="RG33910ST-9B">9b</A> Sahu B. Muruganantham R. Namboothiri INN. Eur. J. Org. Chem. 2007, 2477

<A NAME="RG33910ST-10A">10a</A> Kim C.-S. Russell KC. J. Org. Chem. 1998, 63: 8229

<A NAME="RG33910ST-10B">10b</A> Kumarasinghe ES. Peterson MA. Robins MJ. Tetrahedron Lett. 2000, 41: 8741

For recent reviews, see:

<A NAME="RG33910ST-11A">11a</A> Jones GB. Fouad FS. Curr. Pharm. Des. 2002, 8: 2415

<A NAME="RG33910ST-11B">11b</A> Maretina IA. Trofimov BA. Russ. Chem. Rev. 2006, 75: 825

<A NAME="RG33910ST-11C">11c</A> Shao R.-G. Curr. Mol. Pharm. 2008, 1: 50

<A NAME="RG33910ST-12A">12a</A> Fiandanese V. Bottalico D. Marchese G. Punzi A. Tetrahedron 2008, 64: 53

<A NAME="RG33910ST-12B">12b</A> Fiandanese V. Bottalico D. Marchese G. Punzi A. Tetrahedron 2008, 64: 7301

<A NAME="RG33910ST-13A">13a</A> Sonogashira K. Tohda Y. Hagihara N. Tetrahedron Lett. 1975, 16: 4467

<A NAME="RG33910ST-13B">13b</A> Balova IA. Sorokoumov VN. Morozkina SN. Vinogradova OV. Knight DW. Vasilevsky SF. Eur. J. Org. Chem. 2005, 882

<A NAME="RG33910ST-13C">13c</A> Liang Y. Tao L.-M. Zhang Y.-H. Li J.-H. Synthesis 2008, 3988

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).

<A NAME="RG33910ST-15A">15a</A> Sooloki D. Kennedy VO. Tessier CA. Youngs WJ. Synlett 1990, 427

<A NAME="RG33910ST-15B">15b</A> Sooloki D. Bradshaw JD. Tessier CA. Youngs WJ. Organometallics 1994, 13: 451

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.

<A NAME="RG33910ST-17">17</A> Ebata H. Miyazaki E. Yamamoto T. Takimiya K. Org. Lett. 2007, 9: 4499

<A NAME="RG33910ST-18A">18a</A> Barluenga J. Fananas-Mastral M. Andina F. Aznar F. Valdes C. Organometallics 2008, 27: 3593

<A NAME="RG33910ST-18B">18b</A> Kitagaki S. Katoh K. Ohdachi K. Takahashi Y. Shibata D. Mukai C. J. Org. Chem. 2006, 71: 6908

<A NAME="RG33910ST-18C">18c</A> Shvartsberg MS. Vasilevskii SF. Prihod’ko TA. Izv. Acad. Nauk SSSR, Ser. Khim. 1982, 11: 2524

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.

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.

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.

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.