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Synlett 2003(2): 0241-0243
DOI: 10.1055/s-2003-36795
LETTER
© Georg Thieme Verlag Stuttgart · New York

A Short Three-Component Synthesis of Tricyclic Compounds

Gerhard Hilt*, Tobias J. Korn, Konstantin I. Smolko
Fachbereich Chemie, Philipps-Universität Marburg, Hans-Meerwein-Straße, 35043 Marburg, Germany
Fax: +49(6421)2825677; e-Mail: Hilt@chemie.uni-marburg.de;
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Publication History

Received 30 October 2002
Publication Date:
22 January 2003 (online)

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Abstract

A facile reaction sequence, consisting of a palladium-catalyzed Sonogashira coupling, a cobalt-catalyzed Diels-Alder reaction and a subsequent cyclization initiated by a bromine-lithium exchange reaction, allows a three-component synthesis of tricyclic compounds. Thereby, structurally different functionalized compounds can be generated when functionalized dihalo-arenes, tosyl­ated alkynols and substituted 1,3-dienes are used as starting materials.

Key words

alkynes - catalysis - cobalt - cyclization - Diels-Alder reactions

    References

  • 1a Sonogashira K. In Comprehensive Organic Synthesis   Vol. 3:  Trost B. Flemming I. Pattenden G. Pergamon Press; New York: 1991.  p.521 
    Google Scholar
  • 1b Sonogashira K. In Metal-catalyzed Cross-coupling Reactions   Diederich F. Stang PJ. Wiley-VCH; Weinheim: 1998.  p.203 
    Google Scholar
  • 3a Martinelli MJ. Nayyar NK. Moher ED. Dhokte UP. Pawlak JM. Vaidyanathan R. Org. Lett.  1999,  1:  447 
    CrossrefGoogle Scholar
  • 3b

    The tosylation of propargylic alcohols (n = 1) under these conditions gave the desired products only in moderate yields (up to 25%) accompanied with the corresponding propargylic chloride in up to 35% yield and recovered starting material.
    Crossref
  • For recent cobalt(I)-catalyzed Diels-Alder reactions see:
  • 4a Hilt G. Lüers S. Polborn K. Isr. J. Chem.  2001,  41:  317 
    Article in Thieme ConnectGoogle Scholar
  • 4b Hilt G. Smolko KI. Synthesis  2002,  686 
    Article in Thieme ConnectGoogle Scholar
  • 4c Hilt G. Smolko KI. Synlett  2002,  1081 
    Article in Thieme ConnectGoogle Scholar
  • 6 Parham WE. Bradsher CK. Acc. Chem. Res.  1982,  15:  300 
    CrossrefGoogle Scholar
  • 7a

    Typical procedure: Preparation of 7-methoxy-2,3-dimethyl-1,4,9,10-tetrahydrophenanthrene (Scheme [5] ): To 2-[2-(2-bromo-4-methoxyphenyl)-4,5-dimethyl-1,4-cyclohexadien-1-yl]ethyl 4-methylbenzenesulfonate (134 mg, 0.27 mmol) in anhyd THF (5.0 mL) at -90 °C was added tert-butyllithium (0.4 mL, 1.7 M in THF, 0.56 mmol, 2.1 equiv) in one portion under nitrogen atmosphere. The reaction mixture was allowed to warm up to room temperature. After water addition (1.0 mL), the reaction mixture was extracted with diethyl ether (4 × 50 mL) and the combined organic phases were dried over MgSO4. The solvent was removed and the crude product was purified by column chromatography (SiO2, pentane) affording the desired product (54 mg, 0.23 mmol, 82%) as a colorless crystalline solid.
    1H NMR (300 MHz, CDCl3): δ = 7.13 (d, J = 8.0 Hz, 1 H), 6.75-6.65 (m, 2 H), 3.81 (s, 3 H), 2.94 (t, J = 7.1 Hz, 2 H), 2.84-2.70 (m, 4 H), 2.20 (t, J = 8.3 Hz, 2 H), 1.77 (s, 3 H), 1.72 (s, 3 H); 13C NMR (75 MHz, CDCl3): δ = 157.9, 137.2, 128.8, 128.5, 123.9, 123.5, 122.7, 122.6, 113.6, 110.7, 55.2, 39.0, 33.3, 28.5, 28.1, 18.5, 18.1; MS m/z (%) = 240 (M+, 91), 238(75), 225(100), 210(26), 165(20); HRMS calcd for C17H20O: m/z = 240.1514, found: m/z = 240.1522.

  • 7b For a recent flexible synthesis of phenanthrene derivatives see: Fürstner A. Mamane V. J. Org. Chem.  2002,  67:  6264 ; and references cited therein
    Google Scholar
  • 8 Schlosser M. In Organometallics in Synthesis   Wiley; Chichester: 1994.  p.129-133  
    Google Scholar
2

Besides secondary amines, primary amines such as tert-butylamine, also gave the propargylic amine product in this three component reaction, albeit in lower yields (46%).

5

Typical procedure: Preparation of 3-[2-(2-bromophenyl)-4,5-dimethyl-1,4-cyclohexadien-1-yl]propyl 4-methylbenzenesulfonate (Scheme [4] , n = 3): To 5-(2-bromophenyl)-4-pentynyl-4-methylbenzenesulfonate (321 mg, 0.82 mmol) in dry CH2Cl2 (2.0 mL) were added CoBr2(dppe) (40 mg, 0.07 mmol, 9 mol%), 2,3-dimethyl-1,3-butadiene (145 mg, 1.77 mmol, 2.0 equiv), zinc (300 mg, 4.69 mmol, 5.7 equiv) and ZnBr2 (100 mg, 0.45 mmol, 55 mol%) under nitrogen atmosphere. The reaction mixture was stirred at room temperature overnight. The crude product was purified by column chromatography (SiO2, pentane:diethyl ether = 2:1) affording the desired product (381 mg, 0.80 mmol, 98%) as a colorless oil.
1H NMR (300 MHz, C6D6): δ = 7.70-7.64 (m, 2 H), 7.39 (dd, J = 8.4, 1.1 Hz, 1 H), 7.00-6.85 (m, 2 H), 6.74-6.64 (m, 3 H), 4.77-3.63 (m, 2 H), 3.02-2.84 (m, 1 H), 2.56-2.34 (m, 3 H), 1.82 (s, 3 H), 1.80-1.35 (m, 10 H); 13C NMR (75 MHz, C6D6): δ = 143.9, 143.6, 134.6, 133.0, 131.8, 130.6, 130.4, 129.7, 128.4, 128.1, 127.8, 123.6, 123.0, 122.8, 70.1, 39.4, 36.6, 29.4, 27.2, 21.1, 18.2, 17.9; MS m/z (%) = 474 (M+, 2), 208(15), 194(24), 179(12), 91(11), 74(100); HRMS calcd for C24H27BrO3S: m/z = 474.0864, found: m/z = 474.0811.

9

Typical procedure: Preparation of 1,4,5,6,7,8-hexahydro-2,3-dimethyl-dibenzo[a,c]cyclooctene (Scheme [6] , structure at the bottom): To 4-[2-(2-bromophenyl)-4,5-dimethyl-1,4-cyclohexadien-1-yl]butyl 4-methylbenzenesulfonate (1.282 g, 2.62 mmol) in dry diethyl ether (5.0 mL) at -100 °C tert-butyllithium (3.74 mL, 1.4 M in THF, 5.24 mmol, 2.0 equiv) was added slowly, such that the reaction temperature did not exceed -80 °C. Then, the reaction mixture was allowed to warm up to room temperature. After water (2.0 mL) was added, the reaction mixture was extracted with diethyl ether (4 × 50 mL) and the combined organic phases were dried over MgSO4. The solvent was removed and the crude product was purified by column chromatography (SiO2, pentane) affording the desired product (437 mg, 1.84 mmol, 70%) as a colorless oil.
1H NMR (300 MHz, C6D6): δ = 7.22-7.08 (m, 4 H), 3.16-3.00 (m, 1 H), 2.90-2.75 (m, 1 H), 2.70-2.40 (m, 4 H), 1.98-1.80 (m, 2 H), 1.77 -1.49 (m, 8 H), 1.44-1.11 (m, 2 H); 13C NMR (75 MHz, C6D6): δ = 142.2 (Cq), 141.5(Cq), 132.2(Cq), 129.7 (CH), 128.5 (Cq), 127.4 (CH), 127.1 (CH), 125.8 (CH), 123.7 (Cq), 123.3 (Cq), 38.8 (CH2), 38.6 (CH2), 33.5 (CH2), 32.1 (CH2), 30.4 (CH2), 24.2 (CH2), 18.2 (CH3), 18.1 (CH3); MS m/z (%) = 238 (M+, 100), 223(18), 195(50), 181(57), 165(22); HRMS calcd for C18H22: m/z = 238.1721, found: m/z = 238.1714.
Analytical data for 1,4,6,7-tetrahydro-2,3-dimethyl-dibenzo[a,c]cycloheptene (Scheme [6] , structure at the top):
1H NMR (300 MHz, CDCl3): δ = 7.25-7.02 (m, 4 H), 2.96-2.87 (m, 2 H), 2.83-2.74 (m, 2 H), 2.48 (t, J = 7.1 Hz, 2 H), 2.10-1.98 (m, 2 H), 1.77 (t, J = 6.7 Hz, 2 H), 1.64 (s, 6 H); 13C NMR (75 MHz, C6D6): δ = 142.2 (Cq), 140.3 (Cq), 132.4 (Cq), 128.6 (CH), 128.2 (Cq), 126.1 (CH), 125.9 (CH), 125.4 (CH), 123.8 (Cq), 123.2 (Cq), 39.3 (CH2), 36.9 (CH2), 33.6 (CH2), 32.3 (CH2), 29.8 (CH2), 18.3 (CH3), 18.1 (CH3); MS m/z (%) = 224 (M+, 100), 209(51), 195(24), 181(38), 165(22), 121(27); HRMS calcd for C17H20: m/z = 224.1565, found: m/z = 224.1572.