PDF herunterladen
Synlett 2004(14): 2588-2590  
DOI: 10.1055/s-2004-834817
LETTER
© Georg Thieme Verlag Stuttgart · New York

Stereoselective Intra- and Intermolecular [2+2] Photocycloaddition Reactions of 4-(2′-Aminoethyl)quinolones

Sebastian Brandes, Philipp Selig, Thorsten Bach*
Lehrstuhl für Organische Chemie I, Technische Universität München, Lichtenbergstr. 4, 85747 Garching, Germany
Fax: +49(89)28913315; e-Mail: thorsten.bach@ch.tum.de;
Weitere Informationen

Publikationsverlauf

Received 20 July 2004
Publikationsdatum:
20. Oktober 2004 (online)

    Lizenzen und Reprints Alle Artikel dieser Rubrik

Abstract

The 4-(2′-aminoethyl)quinolones 6, 8 and 9 were prepared starting from 4-(2′-bromoethyl)quinolone (4) in two steps and overall yields of 56-93%. They underwent inter- and intramolecular [2+2] photocycloaddition reactions with an alkene to provide the cyclobutanes 1-3 in racemic form (61-89% yield). The photochemical reaction proceeded with very good chemo-, regio- and stereo­selectivity. It was in one case (8b → 2b) also performed enantioselectively (93% ee).

Key words

asymmetric synthesis - cycloadditions - cyclobutanes - diastereoselectivity - photochemistry - quinolones

    References

  • Reviews:
  • 1a Fleming SA. Bradford CL. Gao JJ. In Molecular and Supramolecular Photochemistry: Organic Photochemistry   Vol. 1:  Ramamurthy V. Schanze KS. Dekker; New York: 1997.  p.187 
    Google Scholar
  • 1b Bach T. Synthesis  1998,  683 
    Google Scholar
  • 1c Pete J.-P. Adv. Photochem.  1996,  21:  135 
    Google Scholar
  • 1d Mattay J. Conrads R. Hoffmann R. In Methoden der Organischen Chemie (Houben-Weyl)   4th ed., Vol. E 21c:  Helmchen G. Hoffmann RW. Mulzer J. Schaumann E. Thieme; Stuttgart: 1995.  p.3085 
    Google Scholar
  • 1e Crimmins MT. Reinhold TL. Org. React.  1993,  44:  297 
    Google Scholar
  • 1f Crimmins MT. Chem. Rev.  1988,  88:  1453 
    Google Scholar
  • 1g Baldwin SW. Org. Photochem.  1981,  5:  123 
    Google Scholar
  • Reviews:
  • 2a Wong HNC. Fitjer L. Heuschmann M. In Methoden der Organischen Chemie (Houben-Weyl)   4th ed., Vol. E 17e:  de Meijere A. Thieme; Stuttgart: 1997.  p.435 
    CrossrefGoogle Scholar
  • 2b Namyslo JC. Kaufmann DE. Chem. Rev.  2003,  103:  1485 
    CrossrefGoogle Scholar
  • 3a Wolfe JF. Trimitsis GB. Morris DR. J. Org. Chem.  1969,  34:  3263 
    Google Scholar
  • 3b Martin O. de la Cuesta E. Avendaño C. Tetrahedron  1995,  51:  7547 
    Google Scholar
  • 3c Uchida M. Tabusa F. Komatsu M. Morita S. Kanabe T. Nakagawa K. Chem. Pharm. Bull.  1985,  33:  3775 
    Google Scholar
  • The formation of photodimer was also observed. The simple diastereoselectivity in the [2+2] photocycloaddition of monosubstituted alkenes was low:
  • 4a Evanega GR. Fabiny DL. J. Org. Chem.  1970,  35:  1757 
    Google Scholar
  • 4b Cantrell TS. J. Org. Chem.  1974,  39:  3063 
    Google Scholar
  • 4c Buchardt O. Christensen JJ. Harrit N. Acta Chem. Scand. B  1976,  30:  189 
    Google Scholar
  • 4d Chiba T. Kato T. Yoshida A. Moroi R. Shimomura N. Momose Y. Naito T. Kaneko C. Chem. Pharm. Bull.  1984,  32:  4707 
    Google Scholar
  • 4e Nonoyama S. Yonezawa N. Saigo K. Hasegawa M. Hirano T. Bull. Chem. Soc. Jpn.  1988,  61:  2387 
    Google Scholar
  • 4f Lewis FR. Reddy GD. Elbert JE. Tillberg BE. Meltzer JA. Kojima M. J. Org. Chem.  1991,  56:  5311 
    Google Scholar
  • 5a Chiba T. Okada M. Kato T. J. Heterocycl. Chem.  1982,  19:  1521 
    Google Scholar
  • 5b Naito T. Momose Y. Kaneko C. Chem. Pharm. Bull.  1982,  30:  1531 
    Google Scholar
  • 5c Sato M. Kawakami K. Kaneko C. Chem. Pharm. Bull.  1987,  35:  1319 
    Google Scholar
  • Intramolecular [2+2] photocycloaddition reactions of 4-alkenyloxy-2-quinolones are known:
  • 6a Kaneko C. Naito T. Somei M. J. Chem. Soc., Chem. Commun.  1979,  804 
    Google Scholar
  • 6b Kaneko C. Suzuki T. Sato M. Naito T. Chem. Pharm. Bull.  1987,  35:  112 
    Google Scholar
  • 8 Review: Grosch B. Bach T. In CRC Handbook of Photochemistry and Photobiology   2nd ed.:  Horspool WM. Lenci F. CRC Press; Boca Raton: 2004.  p.61-1  
    Google Scholar
  • 9 Bach T. Bergmann H. Grosch B. Harms K. Herdtweck E. Synthesis  2001,  1395 
    Artikel in Thieme ConnectGoogle Scholar
  • For investigations on the binding of lactams to complexing agent 10, see:
  • 10a Bach T. Bergmann H. Grosch B. Harms K. J. Am. Chem. Soc.  2002,  124:  7982 
    CrossrefGoogle Scholar
  • 10b Bach T. Grosch B. Strassner T. Herdtweck E. J. Org. Chem.  2003,  68:  1107 
    CrossrefGoogle Scholar
  • 10c Bergmann H. Grosch B. Sitterberg S. Bach T. J. Org. Chem.  2004,  69:  970 
    CrossrefGoogle Scholar
  • 10d Grosch B. Orlebar CN. Herdtweck E. Kaneda M. Wada T. Inoue Y. Bach T. Chem.-Eur. J.  2004,  10:  2179 
    CrossrefGoogle Scholar
7

Representative Procedure for the Intermolecular [2+2] Photocycloaddition:
A solution of quinolone 6 (767 mg, 2.03 mmol, 30.0 mM) and methacrylate (3.67 mL, 3.49 g, 40.5 mmol, 20 equiv, 0.6 M) in toluene (70 mL) was irradiated at 350 nm (RPR-3500 Å) in a merry-go-round apparatus at r.t. for 4 h. After removal of the solvent in vacuo, the crude product was purified by flash chromatography (silica 60: 5 × 20 cm, pentane-EtOAc = 50:50) to give 750 mg (80%) rac-1a as a white foam. 1H NMR (360 MHz, DMSO-d 6, 80 °C): δ = 9.91 (s, 1 H, NH), 7.30-7.20 (m, 3 H, Har), 7.15-7.05 (m, 4 H, Har), 6.99 (virt. t, 3 J = 7.5 Hz, 1 H, Har), 6.89 (d, 3 J = 7.9 Hz, 1 H, Har), 4.27 (s, 2 H, CH 2Ph), 3.65 (s, 3 H, COOCH3), 3.18 (virt. t., 3 J = 10.0 Hz, 1 H, CHCOOMe), 3.01-2.90 (m, 2 H, CHHN, COCH), 2.72-2.58 (m, 2 H, CHCHH, CHHN), 2.38-2.19 (m, 1 H, CHCHH), 2.06-1.93 (m, 1 H, CCHH), 1.86-1.73 (m, 1 H, CCHH), 1.40 [s, 9 H, C(CH3)3].
13C NMR (90.6 MHz, DMSO-d 6, 80 °C): δ = 171.4 (COOMe), 168.8 (CONH), 154.3 (COOtBu), 138.1 (s, Car), 137.0 (s, Car), 127.9 (d, CarH), 127.6 (d, CarH), 127.0 (d, CarH), 126.6 (d, CarH), 125.7 (d, CarH), 124.5 (s, Car), 122.5 (d, CarH), 115.3 (d, CarH), 78.7 [C(CH3)3], 50.9 (COOCH3), 49.7 (CH2Ph), 48.8 (CHCOOMe), 44.8 (CCH2), 41.7 (CH2N), 39.2 (CHCH2), 33.9 (CCH2), 27.7 [C(CH3)3], 24.4 (CCH2). Anal. calcd for C27H32N2O5 (464.55): C, 69.81; H, 6.94; N, 6.03. Found: C, 69.54; H, 6.79; N, 5.87.

11

Enantioselective Intramolecular [2+2] Photocyclo-addition of Compound 8b:
A solution of 8b (20.0 mg, 5.84·10-2 mmol) and 10 (47.6 mg, 1.35·10-1 mmol) in toluene (8 mL) was degassed with argon. After cooling to -60 °C the solution was irradiated with a mercury high pressure arc (Original Hanau TQ 150) using a Duran filter in a merry-go-round apparatus at -60 °C for 8 h. After removal of the solvent in vacuo, the crude product was purified by flash chromatography (silica 60: 2 × 30 cm, CH2Cl2-MeOH = 98:2) to give 15.6 mg (78%) 2b as a white solid (93% ee); 41.3 mg of the chiral complexing agent 10 were recovered. 1H NMR (360 MHz, CDCl3): δ = 9.73 (s, 1 H, NH), 7.16 (dd, 3 J = 6.6 Hz, 3 J = 7.7 Hz, 1 H, Har), 7.08-6.95 (m, 2 H, Har), 6.86 (d, 3 J = 7.7 Hz, 1 H, Har), 3.72-3.63 (m, 2 H, NCH 2CH2), 3.72-3.63 and 3.45 (d, 2 J = 14.0 Hz, 1 H, NCHH), 3.30 (dd, 3 J = 6.9 Hz, 3 J = 10.9 Hz, 1 H, CH), 3.22 and 3.08 (d, 2 J = 14.0 Hz, 1 H, NCHH), 2.62 and 2.54 (virt. t, 3 J = 12.0 and 11.7 Hz, 1 H, CHCHH), 2.44-2.24 (m, 1 H, NCH2CHH), 2.05 (dd, 3 J = 6.9 Hz, 3 J = 12.5 Hz, 1 H, CHCHH), 1.90-1.77 (m, 1 H, NCH2CHH), 1.50 and 1.49 [s, 9 H, C(CH3)3], 0.79 and 0.76 (s, 3 H, CH3). 13C NMR (90.6 MHz, CDCl3): δ = 172.6 and 172.4 (CONH), 155.9 and 155.3 (COOtBu), 136.6 (s, Car), 128.0 (d, CarH), 127.4 and 126.9 (d, CarH), 124.4 and 124.2 (s, Car), 123.3 (d, CarH), 116.1 (d, CarH), 79.7 [C(CH3)3], 50.5 and 48.6 (NCH2), 43.5 and 43.0 (s, Cal), 42.0 (s, Cal), 39.8 and 39.4 (NCH2CH2), 36.1 and 35.5 (CH), 35.2 (CHCH2), 32.4 and 31.9 (NCH2 CH2), 28.5 [C(CH3)3], 23.5 (CH3). [α]D 20 -31.7 (c 0.4, CHCl3). HRMS (EI): m/z calcd for C20H26N2O3: 342.1943. Found: 342.1935.