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DOI: 10.1055/s-2003-36795
A Short Three-Component Synthesis of Tricyclic Compounds
Publication History
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
-
1a
Sonogashira K. In Comprehensive Organic Synthesis Vol. 3:Trost B.Flemming I.Pattenden G. Pergamon Press; New York: 1991. p.521 -
1b
Sonogashira K. In Metal-catalyzed Cross-coupling ReactionsDiederich F.Stang PJ. Wiley-VCH; Weinheim: 1998. p.203 -
3a
Martinelli MJ.Nayyar NK.Moher ED.Dhokte UP.Pawlak JM.Vaidyanathan R. Org. Lett. 1999, 1: 447 -
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.
- For recent cobalt(I)-catalyzed Diels-Alder reactions see:
-
4a
Hilt G.Lüers S.Polborn K. Isr. J. Chem. 2001, 41: 317 -
4b
Hilt G.Smolko KI. Synthesis 2002, 686 -
4c
Hilt G.Smolko KI. Synlett 2002, 1081 - 6
Parham WE.Bradsher CK. Acc. Chem. Res. 1982, 15: 300 -
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 - 8
Schlosser M. In Organometallics in Synthesis Wiley; Chichester: 1994. p.129-133
References
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%).
5Typical 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.
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.