A new approach towards synthesis of benzo[b]fluorene core
Keywords:Synthesis, benzo[b]fluorenone, rearrangement
AbstractNew approach towards synthesis of benzo[b]fluorene core is described. The model compound, 10-methoxy-11H-benzo[b]fluoren-11-one was prepared in five steps starting from dibenzylmalonic acid. The key step was the metal catalyzed rearrangement of 3,3’-dihalo-2,2’-spirobiindan-1,1’-dione. The choice and proper activation of the metal was critical for the assembly of the benzo[b]fluorenone system. The zinc mediated rearrangement of the corresponding dibromo derivative led to the 10-hydroxy-11H-benzo[b]fluoren-11-one derivative in 52% yield. The structure of the product was established by spectroscopic methods and was additionally confirmed by standard methylation reaction to the 10-methoxy derivative, which is known in the literature.
J. Berdy, Handbook of Antibiotic Compounds, CRC Press, Boca Raton, Florida, 1985.
C. Walsh, Antibiotics: Actions, Origins, Resistance, ASM Press, Washington, DC, 2003.
S. J. Gould, N. Tamayo, C. R. Melville, M. C. Cone, Revised structures for the kinamycin antibiotics: 5-diazobenzo[b]fluorenes rather than benzo[b]carbazole cyanamidines, J. Am. Chem. Soc., 116, 2207-08 (1994).
M. P. Gore, S. J. Gould, D. D. Weller, Synthesis of putative intermediates in the biosynthesis of the kinamycin antibiotics: Total synthesis of phenanthroviridin aglycon and related compounds, J. Org. Chem., 57, 2774-83 (1992).
M. C. Cone, P. J. Seaton, K. A. Halley, S. J. Gould, New products related to kinamycin from Streptomyces murayamaensis. I. Taxonomy, production, isolation and biological properties, J. Antibiot., 42, 179-88 (1989).
M. C. Cone, C. R. Melville, M. P. Gore, S. J. Gould, Kinafluorenone, a benzo[b]fluorenone isolated from the kinamycin producer Streptomyces murayamaensis, J. Org. Chem., 58, 1058-61 (1993).
M. P. Gore, S. J. Gould, D. D. Weller, Total synthesis of phenanthroviridin aglycon: The first naturally occurring benzo[b]phenanthridine, J. Org. Chem., 56, 2289-91 (1991).
S. I. Mohri, M. Stefinovic, V. Snieckus, Combined directed Ortho-, remote-metalation and cross-coupling strategies. Concise syntheses of the kinamycin biosynthetic grid antibiotics phenanthroviridin aglycon and kinobscurinone, J. Org. Chem., 62, 7072-73 (1997).
J. L. Morris, C. L. Becker, F. R. Fronczek, W. H. Daly, M. L. McLaughlin, Synthesis of extended linear aromatics using tandem Diels-Alder aromatization reactions, J. Org. Chem., 59, 6484-86 (1994).
K. H. Kim, S. H. Kim, K. Y. Lee, J. N. Kim, Regioselective synthesis of fluorenones via the consecutive IN-mediated barbier reaction, PD-catalyzed cyclization, and friedel-crafts reaction starting from baylis-hillman adducts, Bull. Korean Chem. Soc., 32, 1387-90 (2011).
N. Tamayo, A. M. Echavarren, M. C. Paredes, Palladium-catalyzed coupling of 2-bromonaphthoquinones with stannanes: A concise synthesis of antibiotics WS 5995 A and C and related compounds, J. Org. Chem., 56, 6488-91 (1991).
A. M. Echavarren, N. Tamayo, D. J. Cardenas, Synthesis of antibiotics WS 5995 A and C and related compounds by palladium-catalyzed coupling of 2-bromonaphthoquinones with organostannanes, J. Org. Chem., 59, 6075-83 (1994).
G. Qabaja, G. B. Jones, Annnulattion strategies for benzo[b]fluorene synthesis: Efficient routes to the kinafluorenone and WS-5995 antibiotics, J. Org. Chem., 65, 7187-94 (2000).
A. Martınez, J. C. Barcia, A. M. Estevez, F. Fernández, L. González, J. C. Estévez, R. J. Estévez, A novel approach to the synthesis of benzo[b]fluoren-11-ones, Tetrahedron Lett., 48, 2147–49 (2007).
S. Paul, S. Samanta, J. K. Ray, Palladium-catalyzed one-pot Suzuki coupling followed by arylpalladium addition to aldehyde: A convenient route to fluoren-9-one derivatives, Tetrahedron Lett., 51, 5604-08 (2010).
A. Patra, S. K. Ghorai, S. R. De, D. Mal, Regiospecific Synthesis of Benzo[b]fluorenones via Ring Contraction by Benzil-Benzilic Acid Rearrangement of Benz[a]anthracene-5,6-diones, Synthesis, 2006, 2556-62 (2006).
D. Rodriguez, A. Navarro, L. Castedo, D. Dominguez, C. Saa, Intramolecular [4 + 2] Cycloaddition Reactions of Diarylacetylenes: Synthesis of Benzo[b]fluorene Derivatives via Cyclic Allenes, Org. Lett., 2, 1497-500 (2000).
N. Etomi, T. Kumamoto, W. Nakanishi, T. Ishikawa, Diels-Alder reactions using 4,7-dioxygenated indanones as dienophiles for regioselective construction of oxygenated 2,3-dihydrobenz[ f ]indenone skeleton, Beilstein J. Org. Chem., 4, 1-8 (2008).
E. Gonzalez-Cantalapiedra, Ã. De Frutos, C. Atienza, C. Mateo, A. M. Echavarren, Synthesis of the benzo[b]fluorene core of the kinamycins by arylalkyne-allene and arylalkyne-alkyne cycloadditions, Eur. J. Org. Chem., 1430-43 (2006).
S. Reim, M. Lau, P. Langer, Synthesis of fluorenones based on a ‘[3+3] cyclization/Suzuki cross-coupling/Friedel-Crafts acylation’ strategy, Tetrahedron Lett., 47, 6903–05 (2006).
C. P. Chuang, S. F. Wang, Oxidative Free Radical Reaction between 2-Phenyl-1,4-naphthoquinones and Dimethyl Malonate, Synlett, 1996, 829-30 (1996).
V. B. Birman, Z. Zhao, L. Guo, Benzo[b]fluorenes via Indanone Dianion Annulation. A Short Synthesis of Prekinamycin, Org. Lett., 9, 1223-25 (2007).
M. Watanabe, M. Date, S. Furukawa, Total synthesis of the antibiotic WS-5995A using a key reaction of o-toluamide anions with homophthalic anhydrides, Chem. Pharm. Bull., 37, 292-97 (1989).
G. Qabaja, G. B. Jones, An intramolecular arylation route to the kinafluorenones, Tetrahedron Lett., 41, 5317-20 (2000).
K. C. Nicolaou, H. Li, A. L. Nold, A. Pappo, A. Lenzen, Total synthesis of kinamycins C, F, and J, J. Am. Chem. Soc., 129, 10356–57 (2007).
X. Lei, J. A. Porco, Total Synthesis of the Diazobenzofluorene Antibiotic (-)-Kinamycin C1, J. Am. Chem. Soc., 128, 14790-91 (2006).
H. Koyama, T. Kamikawa, Total syntheses of O4,9-dimethyl stealthins A and C, Tetrahedron Lett., 38, 3973-76 (1997).
F. M. Hauser, M. Zhou, Total synthesis of the structure proposed for prekinamycin, J. Org. Chem., 61, 5722 (1996).
J. Bogdanov, Electron Delocalization in Spiroconjugated Systems, Ph.D. Thesis, The Pennsylvania State University, 2005.
P. Maslak, S. Varadarajan, J. D. Burkey, Synthesis, Structure, and Nucleophile-Induced Rearrangements of Spiroketones, J. Org. Chem., 64, 8201-09 (1999).
W. C. Still, M. Kahn, A. Mitra, Rapid chromatographic technique for preparative separations with moderate resolution, J. Org. Chem., 43, 2923-5 (1978).
R. D. Smith, H. E. Simmons, Norcarane, Organic Syntheses, 41, 72 (1961).
E. Langer, H. Lehner, Transannular .pi.-.pi.-interactions in [2,2]metacyclophane, [2,2]paracyclophane, and 2,2'-spirobiindan, Tetrahedron, 29, 375-83 (1973).
E. Dynesen, Modified synthesis of (+-)-2-2'-spirobi[indan]-1,1'-dione, Acta Chem. Scand., 26, 850-2 (1972).
A. Wurtz, Ueber eine neue Klasse organischer Radicale, Annalen der Chemie und Pharmacie, 96, 364-75 (1855).
N. G. Connelly, W. E. Geiger, Chemical Redox Agents for Organometallic Chemistry, Chem. Rev., 96, 877-910 (1996).
E. Erdik, Organozinc reagents in organic synthesis, CRC Press, Boca Raton, Florida, 1996.
K. C. Tang, M. J. Chang, T. Y. Lin, H. A. Pan, T. C. Fang, K. Y. Chen, W. Y. Hung, Y. H. Hsu, P. T. Chou, Fine tuning the energetics of excited-state intramolecular proton transfer (ESIPT): white light generation in a single ESIPT system, J. Am. Chem. Soc., 133, 17738-45 (2011).
How to Cite
The authors agree to the following licence: Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)
- Share — copy and redistribute the material in any medium or format
- Adapt — remix, transform, and build upon the material
- for any purpose, even commercially.
Under the following terms:
Attribution — You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use.
- NonCommercial — You may not use the material for commercial purposes.