Rearrangement of aryl geranyl ethers

Article abstract of DOI:10.1080/00397911.2011.579799

This article describes the thermal rearrangement reactions of aryl geranyl ethers. These reactions depend on the structure of the aryl moiety of the substrate and the reaction conditions used. The naphthyl ethers underwent a [1,3]-alkyl shift, followed by acid-catalyzed intramolecular cyclization. The microwave-assisted rearrangement of isoquinolinyl ether showed a pattern of an abnormal Claisen rearrangement. The multi step rearrangement of the quinolyl ether afforded a spiro compound. These new reactions were used to synthesize novel heterocyclic compounds.

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Rearrangement of Aryl Geranyl Ethers
Mercedesz Törincsi a , Pál Kolonits a , Jenő Fekete b & Lajos Novak a
a Department of Organic Chemistry and Technology, Research Group
for Alkaloid Chemistry, Budapest University of Technology and
Economics, Hungarian Academy of Sciences, Budapest, Hungary
b Department of Inorganic and Analytical Chemistry, Budapest
University of Technology and Economics, Budapest, Hungary
Accepted author version posted online: 10 Jan 2012.Version of
record first published: 17 Aug 2012.
To cite this article: Mercedesz Törincsi, Pál Kolonits, Jenő Fekete & Lajos Novak (2012):
Rearrangement of Aryl Geranyl Ethers, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 42:21, 3187-3199
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Synthetic Communications1, 42: 3187–3199, 2012
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2011.579799
REARRANGEMENT OF ARYL GERANYL ETHERS
1
Mercedesz Torincsi, Pal Kolonits, Jeno Fekete, and
1
2
´
}
¨
Lajos Novak1
1Department of Organic Chemistry and Technology, Research Group for
Alkaloid Chemistry, Budapest University of Technology and Economics,
Hungarian Academy of Sciences, Budapest, Hungary
2Department of Inorganic and Analytical Chemistry, Budapest University of
Technology and Economics, Budapest, Hungary
GRAPHICAL ABSTRACT
Abstract This article describes the thermal rearrangement reactions of aryl geranyl ethers.
These reactions depend on the structure of the aryl moiety of the substrate and the reaction
conditions used. The naphthyl ethers underwent
a [1,3]-alkyl shift, followed by
acid-catalyzed intramolecular cyclization. The microwave-assisted rearrangement of iso-
quinolinyl ether showed a pattern of an abnormal Claisen rearrangement. The multi step
rearrangement of the quinolyl ether afforded a spiro compound. These new reactions were
used to synthesize novel heterocyclic compounds.
Keywords Benzo[h]chromene; benzo[a]xanthene; furo[3,2-f]isoquinoline; furo[3,2-h]
quinoline; microwave-assisted synthesis; rearrangement
Received February 1, 2011.
Address correspondence to Lajos Novak, Department of Organic Chemistry and Technology,
Research Group for Alkaloid Chemistry, Budapest University of Technology and Economics,
´
Hungarian Academy of Sciences, Gellert ter 4, 1111 Budapest, Hungary. E-mail: lnovak@mail.bme.hu
´
3187

¨
M. TORINCSI ET AL.
3188
INTRODUCTION
There has been substantial interest in aryl geranyl ethers because some of them
have been reported to display a range of interesting biological properties. Geranyl
phenyl ethers were isolated from the New Zealand liverwort (Trichocolea mollissi-
ma)[1a] and showed cytotoxic effects against kidney cells and in AIDS-related lym-
phoma screens.[1b] Furthermore, some of their representatives possessed
antimicrobial and antioxidative activities.[1c]
Several phenyl geranyl ethers were prepared and tested for inhibition of insect
growth. The epoxide of these compounds showed significant insect juvenile hormone
activity.[2a] The geranyl ethers of naphthalene-2-ol and quinolin-8-ol had only mod-
erate morphogenetic activity.[2b] Furanone, coumarin and naphthol derivatives con-
taining a geraniol-like fragment have been shown to process significant in vitro
cytostatic activity.[3] Moreover, the geranyloxy-coumarin derivatives showed anti-
microbial and spasmolytic activity.[2c] Recently Nishiyama et al. published that the
geranyl derivatives of isoquinoline alkaloids have been shown to possess biological
activities.[2d]
On the other hand, the chemical properties of geranyl ethers are also important
in connection with terpenoid chemistry.
Recently we have developed efficient methods for the preparation of heteroaro-
matic compounds by aromatic Claisen rearrangement and subsequent cyclization.[4]
As an extension of this research, we have examined the rearrangement reactions of
aryl and hetaryl geranyl ethers. We report here the results and the synthesis of new
heterocyclic rings.
RESULT AND DISCUSSION
Rearrangement of Geranyl Naphthyl Ethers
Geranyl naphth-1-yl ether (1) was prepared from naphthalene-1-ol and geranyl
bromide using literature procedure.[5] In the presence of PTSA, the thermal
rearrangement of this ether 1 gave two unexpected products 4 and 5 (Scheme 1).
A plausible reaction path for the formation of benzo[c]xanthene 4 and benzo[h]chro-
mene 5 may be a [1,3]-alkyl shift, followed by acid-catalyzed intramolecular cycliza-
tions (3a ! 5 and 3b ! 4, respectively).
At elevated temperature the rearrangement of ether 1 led to a para-substituted
naphthalene derivative 7. Here, a [3,3]-sigmatropic rearrangement (Claisen-
rearrangement) afforded intermediate 6, which then underwent an another [3,3]-
rearrangement (Cope-rearrangement) to yield compound 7. Intermediate 6 was
isolated as its acetate by Karanewsky and Kishi. They performed the thermal
rearrangement reaction in the presence of acetic anhydride and potassium acetate.[5].
In microwave oven at higher temperature (170 ꢀC), ether 1 decomposed and
only naphthalene-1-ol was isolated.
Similar results were obtained with geranyl naphth-2-yl ether (8)[2b,c] (Scheme 2).
In toluene solution, the acid-initiated rearrangement reaction afforded intermediate
9, which underwent subsequent acid-catalyzed cyclizations (9 ! 10b ! 11 and
10a ! 12) to yield benzo[a]xanthene 11 (as a mixture of cis and trans-isomers) and
benzo[f]chromene 12, respectively. Attempted thermal rearrangement in boiling

REARRANGEMENT OF ARYL GERANYL ETHERS
3189
Scheme 1. Rearrangement of naphth-1-yl geranyl ether: (a) PTSA, toluene, rt, 7 days; (b) reflux in chlor-
obenzene, 24 h. (Figure is provided in color online.)
chlorobenzene or under microwave irradiation resulted the decomposition of ether 8,
and naphthalene-2-ol was isolated.
Rearrangement of Geranyl Isoquinolinyl Ether
Treatment of isoquinolin-5-ol (13)[6] with sodium hydride afforded the corre-
sponding anion, which was then reacted with geranyl bromide. The product 14
underwent rearrangement in a microwave oven to furnish furo[2,3-f]isoquinoline
(18) in good yield. Here, microwave heating was superior to conventional external
heating, since in boiling solvents we got significantly lower yield.
A plausible mechanism for the formation of compound 18 was based on an
abnormal Claisen rearrangement depicted in Scheme 3.[7] Namely, [3,3]-sigmatropic
rearrangement of ether 14 afforded intermediate 15, which then underwent a
homo[1,5]-hydrogen shift to give intermediate 16. Further [1,5]-H migration on
the latter led to the formation of compound 17, which by intermolecular cyclization
furnished 18 as a 3:2 mixture of cis and trans-isomers. This mixture was separated by
preparative high-performance liquid chromatography (HPLC) and their structures
were established by NMR analysis.

¨
M. TORINCSI ET AL.
3190
Scheme 2. Rearrangement of naphth-2-yl geranyl ether: (a) PTSA, toluene, rt, 7 days. (Figure is provided
in color online.)
Scheme 3. Rearrangement of isoquinolin-5-yl geranyl ether: (a) NaH, geranyl bromide; (b) microwave
irradiation, 180 ꢀC, 20 h. (Figure is provided in color online.)

REARRANGEMENT OF ARYL GERANYL ETHERS
3191
Scheme 4. Rearrangement of quinolin-8-yl geranyl ether: (a) microwave irradiation, 160 ꢀC, 8 h; (b)
H2SO4, 100 ꢀC, 1 h; (c) PTSA, toluene, rt, 40 h. (Figure is provided in color online.)
Rearrangement of Geranyl Quinolinyl Ether
Geranyl quinolin-8-yl ether (19) was prepared from quinolin-8-ol and geranyl
bromide according to the published procedure.[5] Thermal rearrangement of 19 in
boiling toluene led to the formation of the Claisen product 20 in 28% yield. The
microwave-assisted reaction gave a better result, and compound 20 was isolated in
61% yield.
Surprisingly, acid-catalyzed intramolecular cyclization of compound 20
afforded a stereoisomeric mixture of spiro compounds (23 and 24), which were sepa-
rated and analyzed by NMR. These unexpected products took their origins from
consecutive [1,2]-alkyl migration, [1,2]-H shift, and cyclization reaction.[8]
Reaction of ether 19 with sulfuric acid at higher temperature afforded com-
pound 25 as the result of acid-catalyzed ring closure of the geranyl moiety.
CONCLUSIONS
In thermal rearrangements a -naphthyl geranyl ether (1) and b-naphthyl gera-
nyl ether (8) underwent [1,3]-alkyl shift followed by acid-catalyzed cyclization to give
benzoxanthene and benzochromane derivatives (4, 11, 5, 12) in moderate yields.

¨
M. TORINCSI ET AL.
3192
Toward improvement of the yields, we performed these reactions with microwave
irradiation. However, above 170 ꢀC used in the experiments, these naphthyl ethers
decomposed. In spite of the instability, at the boiling point of chlorobenzene
(132 ꢀC) a -naphthyl geranyl ether (1) afforded a p-substituted a -naphthol derivative
(7), as the result of subsequent Claisen and Cope rearrangements.
In the microwave-assisted reaction, isoquinolin-5-yl geranyl ether (14) yielded
furo[2,3-f]isoquinoline in an abnormal Claisen rearrangement. Here, microwave
heating was better then boiling chlorobenzene, because the yield was significantly
greater (44% and 72.8%, respectively).
Rearrangement reaction of geranyl quinolin-8-yl ether (19) gave the expected
Claisen product (20), The microwave-assisted reaction was superior to thermal reac-
tion, and we isolated compound 20 in good yield. The acid-catalyzed reaction of this
product gave a mixture of spiro-compounds by [1,2]-alkyl migration, [1,2]-H shift,
and cyclization.
Heating ether 19 with sulfuric acid furnished quinoline derivative 25 through
the cyclization of the geranyl moiety.
These new rearrangement and cyclization reactions were used for the prep-
aration of new benzo[c]xanthene, benzo[h]chromene, benzo[a]xanthene, benzo[f]-
chromene, furo[2,3-f]isoquinoline, and spiro-[3,2-h]quinoline derivatives. These
new compounds could have interesting biological properties.
EXPERIMENTAL
Material and Physical Measurements
Solvents for synthesis were used as received from commercial suppliers, and
no further attempts were made to purify or dry them. Melting points were determined
on a Buchi apparatus and are uncorrected. Infrared (IR) spectra were recorded on
¨
Bruker Alpha FT spectrophotometer. 1H NMR and 13C NMR spectra were obtained
on a Bruker DRX-500 spectrometer operating at 500 MHz and 125 MHz, respect-
ively. All NMR spectra are reported in parts per million (ppm) relative to tetra-
methylsilane (TMS). Merck precoated silica-gel 60 F254 plates were used for
analytical thin-layer chromatography (TLC) and Kieselgel 60 for column chromato-
graphy. Liquid column chromatography and mass spectra were conducted on Agilent
1200 HPLC and Agilent 6140 quadrupole LC=MS (column: Gemini 3m C18,
50 ꢁ 3 mm; solvent: H2O=cericammonium nitrate=trifluroacetic acid 100:5:0.05)
instruments. Gas chromatography–mass spectrometry (GC-MS) were recorded on
Agilent 7890A GC and Agilent 5975C inert MSD with triple-axis detector (column:
Restek Rxi-5 Sil MS, 15 m ꢁ 0.25). Microwave irradiation was carried out using a
CEM Explorer microwave reactor equipped with automatic temperature controller
(IR temperature sensor) and auto sampler (CEM Corporation, Matthews, NC).
Rearrangement of Naphth-1-yl Geranyl Ether (1)
1-((E)-3,7-Dimethylocta-2,6-dienyloxy)naphthalene (1). This compound
1
was prepared by literature procedure.[5] Yield: 84%; yellow oil; H NMR (CD0Cl3):
1.61 (s, 3H, CH3), 1.68 (s, 3H, CH3), 1.74 (s, 3H, CH3), 2.10 (m, 2H, C4 -H),

REARRANGEMENT OF ARYL GERANYL ETHERS
3193
0
0
2.14 (m, 2H, C5 -H), 4.69 (d, J ¼ 6.2 Hz, 2H, OCH2), 5.11 (t, J ¼ 6.5 Hz, 1H, C6 -H),
0
5.60 (t, J ¼ 6.2 Hz, 1H, C2 -H), 6.78 (d, J ¼ 7.5 Hz, 1H, C2-H), 7.33 (t, J ¼ 7.5 Hz, 1H,
C3-H), 7.38 (m, 1H, C4-H), 7.43 (m, 2H, C6-H and C7-H), 7.75 (d, J ¼ 7.5 Hz, 1H,
C5-H), 8.29 (d, J ¼ 7.7 Hz, 1H, C8-H). 13C NMR (CDCl3): 16.70 (CH3), 17.71
(CH3), 25.70 (CH3), 26.37 (C-50), 39.56 (C-40), 65.20 (C-10), 104.94 (C-2), 119.88
(C-20), 120.06 (C-4), 122.24 (C-8), 123.89 (C-60), 125.01 (C-7), 125.83 (C-3), 125.90
(C-8a), 126.28 (C-6), 127.39 (C-5), 131.72 (C-70), 134.56 (C-4a), 140.67 (C-30),
154.71 (C-1).
2-Methyl-2-(4-methyl-3-penten-1-yl)-3,4-dihydro-2H-benzo[h]chromene
(5) and cis-8,8,11a-trimethyl-7a,8,9,10,11a-hexahydro-7H-benzo[c]xanthene
(4). A mixture of ether 1 (3.85 g, 13.7 mmol) and PTSA (2.60 g, 13.7 mmol) in
toluene (40 mL) was stirred at rt for 7 days. The mixture was quenched with water
(30 mL), and the organic layer was separated, dried (MgSO4), and concentrated.
The residue was purified by column chromatography (hexane–EtOAc 5:0.1) to
afford compounds 5 and 4.
1
Yield 5: 1.3 g (34%), colorless oil; Rf ¼ 0.58 (hexane–EtOAc 5:0.1). H NMR
(CDCl3): 1.36 (s, 3H, CH3), 1.59 (s, 3H, CH3), 1.66 (s, 3H, CH3), 1.67 (m, 1H,
0
0
C1 -H),0 1.76 (m, 1H, C1 -H), 1.84 (m, 1H, C3-H), 1.91 (m, 1H, C3-H), 2.20 (m,
0
2H, C2 -H), 2.84 (m, 2H, C4-H), 5.14 (t, J ¼ 6 Hz, 1H, C3 -H), 7.13 (d, J ¼ 7 Hz,
1H, C5-H), 7.28 (d, J ¼ 7 Hz, 1H, C6-H), 7.38 (m, 1H, C8-H), 7.40 (m, 1H, C9-H),
7.71 (m, 1H, C7-H), 8.20 (m, 1H, C10-H). 13C NMR (CDCl3): 17.57 (CH3), 22.32
(C-20), 22.44 (C-4), 23.85 (CH3), 25.66 (CH3), 31.23 (C-3), 39.89 (C-10), 76.26
(C-2), 114.42 (C-4a), 118.79 (C-6), 121.60 (C-10), 124.38 (C-30), 124.85 (C-9),
125.42 (C-8), 125.74 (C-10a), 127.30 (C-7), 127.68 (C-5), 131.51 (C-40), 133.32
(C-6a), 148.56 (C-10b). Anal. calcd. for C20H24O: C, 85.67; H, 8.63. Found: C,
85.51; H, 8.74.
1
Yield 4: 0.54 g (14%), colorless oil; Rf ¼ 0.43 (hexane–EtOAc 5:0.1). H NMR
(CDCl3): 0.60 (s, 3H, CH3), 0.97 (s, 3H, CH3), 1.24 (s, 3H, CH3), 1.30 (m, 1H, C9-H),
1.45 (m, 1H, C9-H), 1.50 (m, 2H, C7a-H and C10-H), 1.54 (m, 1H, C11-H), 1.96 (m,
1H, C10-H), 2.20 (m, 1H, C11-H), 2.83 (d, J ¼ 17.5 Hz, 1H, C7-H), 3.13 (dd, J ¼ 17.5
and 8.0 Hz, 1H, C7-H), 7.14 (d, J ¼ 8.3 Hz, 1H, C6-H), 7.29 (d, J ¼ 8.3 Hz, 1H,
C5-H), 7.39 (m, 2H, C2-H and C3-H), 7.72 (dd, J ¼ 8 and 2 Hz, 1H, C4-H), 8.20
(dd, J ¼ 7 and 2 Hz, 1H, C1-H). 13C NMR (CDCl3): 18.21 (C-10), 21.33 (CH3),
24.09 (C-7), 27.04 (CH3), 32.36 (CH3), 34.06 (C-8), 39.62 (C-11), 41.75 (C-9),
44.45 (C-7a), 75.63 (C-11a), 115.32 (C-6a), 118.99 (C-5), 121.59 (C-1), 124.70
(C-2), 125.24 (C-3), 125.70 (C-12b), 127.32 (C-4), 127.37 (C-6), 133.04 (C-4a),
149.06 (C-12a). MS (m=z): 280 (Mþ, 26%), 195 (Mþ- C6H13, 3%), 157 (100%). Anal.
calcd. for C20H24O: C, 85.67; H, 8.63. Found: C, 85.44; H, 8.79.
4-[(2E)-2,7-Dimethyl-2,6-octadien-1-yl]-1-naphthol (7). A solution of
ether 1 (1.0 g, 3.57 mmol) in chlorobenzene (20 mL) was heated at reflux for 24 h.
The solvent was evaporated under reduced pressure, and the crude product was
purified by column chromatography (hexane–EtOAc 6:1). Yield: 0.34 g (34%); light
brown oil; Rt ¼ 0.45 (hexane–EtOAc 5:1). IR (film): 3390 (OH), 1586, 1515, 1439,
1
1380, 1267, 1050 cmꢂ1. H NMR (CDCl3): 1.58 (s, 3H, CH3), 1.66 (s, 3H, CH3),
0
0
1.76 (s, 3H, CH3), 2.06 (m, 2H, C4 -H), 2.10 (m, 2H, C5 -H), 3.68 (d, J ¼ 6.8 Hz,
0
0
0
2H, C1 -H), 5.09 (t, J ¼ 6.5 Hz, 1H, C6 -H), 5.38 (t, J ¼ 6.8 Hz, 1H, C2 -H), 5.39

¨
M. TORINCSI ET AL.
3194
(br s, 1H, OH), 6.70 (d, J ¼ 7.5 Hz, 1H, C2-H), 7.13 (d, J ¼ 7.5 Hz, 1H, C3-H), 7.47 (t,
J ¼ 7.5 Hz, 1H, C7-H), 7.51 (t, J ¼ 7.5 Hz, 1H, C6-H), 7.95 (d, J ¼ 8.0 Hz, 1H, C5-H),
8.21 (d, J ¼ 8.0 Hz, 1H, C8-H). 13C NMR (CDCl3): 16.20 (CH3), 17.70 (CH3), 25.76
(CH3), 26.61 (C-50), 31.17 (C-10), 39.69 (C-40), 108.20 (C-2), 122.18 (C-8), 123.23
(C-20), 124.08 (C-5), 124.29 (C-60), 124.80 (C-8a), 124.83 (C-7), 125.24 (C-3),
126.21 (C-6), 130.15 (C-4), 131.47 (C-70), 133.06 (C-4a), 136.06 (C-30), 150.01
(C-1). MS (m=z): 280 (Mþ, 28%), 265 (Mþ-CH3, 5), 211 (Mþ-C5H9, 34), 195 (20),
181 (31), 157 (100). Anal. calcd. for C20H24O: C, 85.67; H, 8.63. Found: C, 85.41;
H, 8.48.
Rearrangement of Naphth-2-yl Geranyl Ether (8)
2-f[(2E)-3,7-Dimethyl-2,6-octadien-1-yl]oxygnaphthalene (8). This com-
pound was prepared from naphthalene-2-ol and geranyl bromide by the literature
procedure.[2b,c] Yield: 87%; white crystals; mp 28–32 ꢀC; It was described as an oil.
1H NMR (CDCl3): 1.61 (s, 3H, CH3), 1.67 (s, 3H, CH3), 1.78 (s, 3H, CH3), 2.11
0
0
0
(m, 2H, C4 -H), 2.13 (m, 2H, C5 -H), 4.65 (d, J ¼ 6.5 Hz, 2H, C1 -H), 5.10 (t,
0
0
J ¼ 6.5 Hz, 1H, C6 -H), 5.56 (t, J ¼ 6.5 Hz, 1H, C2 -H), 7.15 (s, 1H, C1-H), 7.16
(dd, J ¼ 8 and 1.5 Hz, 1H, C3-H), 7.32 (t, J ¼ 8 Hz, 1H, C6-H), 7.42 (t, J ¼ 8 Hz,
1H, C7-H), 7.71 (d, J ¼ 8 Hz, 1H, C8-H), 7.72 (d, J ¼ 8 Hz, 1H, C4-H), 7.75 (d,
J ¼ 8 Hz, 1H, C5-H). 13C NMR (CDCl3): 16.75 (CH3), 17.73 (CH3), 25.69 (CH3),
26.37 (C-50), 39.62 (C-40), 64.94 (C-10), 106.85 (C-1), 119.17 (C-3), 119.46 (C-20),
123.53 (C-6), 123.85 (C-60), 126.30 (C-7), 126.75 (C-8), 127.66 (C-5), 128.96
(C-4a), 129.34 (C-4), 131.84 (C-70), 134.60 (C-8a), 141.34 (C-30), 156.89 (C-2).
7a,11,11-Trimethyl-8,9,10,11,11a,12-hexahydro-7aH-benzo[a]xanthene
(11) and 3-Methyl-3-(4-methyl-3-penten-1-yl)-2,3-dihydro-1Hbenzo[f]chromene
(12). A mixture of ether 8 (3.66 g, 13.1 mmol) and PTSA (2.38 g, 13.7 mmol) in tolu-
ene (40 mL) was stirred at rt for 7 days. The mixture was quenched with water
(30 mL), and the organic layer was separated, dried (MgSO4), and concentrated.
The residue was purified by column chromatography (hexane–EtOAc 5:0.1) to
afford compounds 11 and 12.
Yield 11: 1.3 g (35.5%); white crystals; mp 95–97 ꢀC; Rf ¼ 0.33 (hexane–EtOAc
5:0.1). IR (KBr): 1623, 1577, 1456, 1432, 1392, 1374, 1263, 1228, 1158, 1092 cmꢂ1. 1H
NMR (CDCl3):0.61 (s, 3H, CH3), 1.00 (s, 3H, CH3), 1.23 (s, 3H, CH3), 1.31 (m, 1H,
C10-H), 1.47 (m, 2H, C10-H), 1.53 (m, 1H, C8-H), 1.60 (m, 1H, C11a-H), 1.92 (m, 1H,
C9-H), 2.08 (m, 1H, C8-H), 3.10 (m, 2H, C12-H), 6.99 (d, J ¼ 8.8 Hz, 1H, C6-H), 7.32
(t, J ¼ 7.5 Hz, 1H, C3-H), 7.48 (d, J ¼ 7.5 Hz, C2-H), 7.58 (d, J ¼ 8.8 Hz, C5-H), 7.74
(d, J ¼ 8 Hz, C4-H), 7.85 (d, J ¼ 8 Hz, C1-H). 13C NMR (CDCl3): 18.11 (C-9), 20.62
(C-12), 21.23 (CH3), 26.64 (CH3), 32.48 (CH3), 34.13 (C-11), 39.47 (C-8), 41.60
(C-10), 44.47 (C-11a), 75.31 (C-7a), 113.30 (C-12a), 119.60 (C-6), 121.75 (C-1),
122.81 (C-3), 126.02 (C-2), 127.27 (C-5), 128.46 (C-4), 128.89 (C-4a), 132.71
(C-12a), 151.90 (C-6a). MS (m=z): 280 (Mþ, 22%), 195 (Mþ-C6H13, 7%), 157 (Mþ-
C9H11, 100%). Anal. calcd. for C20H24O: C, 85.67; H, 8.63. Found: C, 85.91; H, 8.44.
Yield 12: 0.27 g (10%); colorless oil; Rf ¼ 0.30 (hexane–EtOAc 5:0.1). IR (KBr):
1
1623, 1575, 1508, 1450, 1432, 1392, 1377, 1207, 1093 cmꢂ1. H NMR (CDCl3): 1.34
0
(s, 3H, CH3), 1.60 (s, 3H, CH3), 1.63 (m, 1H, C1 -H), 1.66 (s, 3H, CH3), 1.70

REARRANGEMENT OF ARYL GERANYL ETHERS
3195
0
0
(m, 1H, C1 -H), 1.93 (m, 1H, C2-H), 1.98 (m, 1H, C2-H), 2.13 (m, 2H, C2 -H), 3.01 (t,
0
J ¼ 6.5 Hz, 2H, C1-H), 5.10 (t, J ¼ 7 Hz, 1H, C3 -H), 7.03 (d, J ¼ 8.9 Hz, 1H, C5-H),
7.31 (t, J ¼ 7.5 Hz, 1H, C8-H), 7.46 (t, J ¼ 8 Hz, 1H, C9-H), 7.60 (d, J ¼ 8.9 Hz, 1H,
C6-H), 7.73 (d, J ¼ 8.1 Hz, 1H, C7-H), 7.80 (d, J ¼ 8.4 Hz, 1H, C10-H). 13C NMR
(CDCl3): 17.60 (CH3), 19.00 (C-1), 22.31 (C-20), 23.85 (CH3), 25.66 (CH3), 30.95
(C-2), 39.07 (C-10), 75.81 (C-3), 112.56 (C-10b), 119.82 (C-5), 121.80 (C-10),
122.88 (C-8), 124.25 (C-30), 126.14 (C-9), 127.66 (C-6), 128.37 (C-7), 128.67
(C-6a), 131.60 (C-40), 133.05 (C-10a), 151.30 (C-4a). Anal. calcd. for C20H24O:
C, 85.67; H, 8.63. Found: C, 85.81; H, 8.34.
Rearrangement of Isoquinolin-5-yl Geranyl Ether (14)
5-f[(2E)3,7-Dimethyl-2,6-octadien-1-yl]oxygisoquinoline (14). 5-Hydro-
xyisoquinoline (13; 1.6 g, 11.4 mmol) was added to a cold (0 ꢀC) and stirred suspen-
sion of NaH (0.6 g, 60% in paraffin oil, 15 mmol) in DMF (10 mL) during 20 min,
and the mixture was stirred at rt for 1 h. After adding geranyl bromide (3.48 g,
16.1 mmol), the resulting mixture was stirred at rt for 18 h. The reaction mixture
was poured into water, extracted with ether (three times, 30 mL each), and the
combined organic layers were washed with brine and dried (MgSO4). Evaporation
of the solvent in vacuum afforded a light brown oil, which was purified by column
chromatography.
Yield: 2.0 g (64%); yellow oil; Rf ¼ 0.73 (CH2Cl2–acetone 3:1). IR (KBr): 1625,
1582, 1491, 1433, 1390, 1369, 1275, 1247, 1171, 1105, 1063 cmꢂ1. 1H NMR (CDCl3):
0
1.62 (s, 3H, CH3), 1.68 (s, 3H, CH3), 1.78 (s, 3H, CH3), 2.14 (m, 4H, C4 -H and
0
0
C5 -H), 4.74 (d, J ¼ 6 Hz, 2H, OCH2), 5.10 (m, 1H, C6 -H), 5.58 (t, J ¼ 6 Hz, 1H,
0
C2 -H), 7.02 (d, J ¼ 7.2 Hz, 1H, C6-H), 7.52 (m, 2H, C8-H), 8.08 (d, J ¼ 5.7 Hz,
1H, C4-H), 8.51 (d, J ¼ 5.7 Hz, 1H, C3-H), 9.21 (s, 1H, C1-H). 13C NMR (CDCl3):
16.77 (CH3), 17.73 (CH3), 25.70 (CH3), 26.30 (C-50), 39.54 (C-40), 65.46 (C-10),
109.10 (C-6), 115.60 (C-4), 119.12 (C-20), 119.23 (C-8), 123.71 (C-60), 127.67 (C-7),
128.90 (C-4a), 129.44 (C-8a), 131.91 (C-70), 141.61 (C-30), 141,75 (C-3), 151.32
(C-1), 153.73 (C-5). Anal. calcd. for C19H23NO: C, 81.10; H, 8.24; N, 4.98. Found:
C, 80.92; H, 8.42; N, 4.76.
2,3-Dimethyl-2-(4-methyl-3-penten-1-yl)-2,3-dihydrofuro[2,3-f]isoquinoline
(18). Ether 14 (0.5 g, 1.7 mmol) was heated at 180 ꢀC for 20 h in a microwave oven.
After cooling, the reaction mixture was dissolved in a mixture of CH2Cl2–MeOH
(10:1) and purified by column chromatography using CH2Cl2–MeOH (2.5:0:1) as
eluent. Yield: 0.364 g (72.8%); light yellow oil; Rf ¼ 0.42 (CHCl3–MeOH 25:1). We
have not been able to separate this diastereoisomeric mixture.
HPLC: tR ¼ 2.490 and 2.395 min (H2O–acetonitrile–TFA 10:0.5:0.0075).
1H NMR (CDCl3): 1.31, 1.33 (d, 3H,CH3), 1.39, 1.54 (s, 3H, CH3), 1.58 (s, 3H,
0
0
CH3), 1.66 (s, 3H, CH3), 1.8–1.9 (m, 2H, C1 -H), 2.1–2.2 (m, 2H, C2 -H), 3.39, 3.43
0
(m, 1H, C3-H), 5.12 (m, 1H, C3 -H), 7.40 (m, 1H, C4-H), 7.51 (m, 1H, C5-H), 7.75
(m, 1H, C9-H), 8.43 (m, 1H, C8-H). 13C NMR (CDCl3): 14.55, 15.41 (CH3), 17.63
(CH3), 20.25, 25.15 (CH3), 25.56 (CH3), 22.52, 22.74 (C-20), 34.90, 41.62 (C-10),
44.90, 47.35 (C-3), 92.86, 93.22 (C-2), 114.94, 115.04 (C-9), 119.58, 119.65 (C-5),
122.95, 123.04 (C-9a), 123.86 (C-30), 123.92, 124.13 (C-4), 129.04 (C-5a), 131.22

¨
M. TORINCSI ET AL.
3196
(C-3a), 131.91 (C-40), 141.15, 141.17 (C-8), 151.83, 151.89 (C-6), 152.49, 152.54
(C-9b). MS (m=z): 281 (Mþ, 100%), 266 (Mþ-CH3, 34), 238 (Mþ-C3H7, 35), 210
(Mþ-C5H11, 100). Anal. calcd. for C19H23NO: C, 81.10; H, 8.24; N, 4.98. Found:
C, 80.82; H, 8.47; N, 4.69.
Rearrangement of Quinolin-8-yl Geranyl Ether (19)
8-f[(2E)-3,7-Dimethyl-2,6-octadien-1-yl]oxygquinoline (19). This com-
pound was prepared according to the method used by Karanewsky and Kishi[5] in
1
51% yield. H NMR (CDCl3): 1.59 (s, 3H, CH3), 1.65 (s, 3H, CH3), 1.78 (s, 3H,
0
0
CH3), 2.08 (m, 2H, C4 -H), 2.12 (m, 2H, C5 -H), 4.87 (d, J ¼ 6.2 Hz, 2H, OCH2),
0
0
5.09 (t, J ¼ 6 Hz, 1H, C6 -H), 5.66 (t, J ¼ 6.2 Hz, 1H, C2 -H), 7.05 (d, J ¼ 8 Hz, 1H,
C7-H), 7.36 (d, J ¼ 8 Hz, 1H, C5-H), 7.40 (m, 1H, C3-H), 7.43 (t, J ¼ 8 Hz, C6-H),
8.11 (d, J ¼ 8 Hz, 1H, C4-H), 8.95 (d, J ¼ 3 Hz, 1H, C2-H). 13C NMR (CDCl3):
16.79 (CH3), 17.71 (CH3), 25.69 (CH3), 26.27 (C-50), 39.57 (C-40), 65.97 (C-10),
109.06 (C-7), 119.38 (C-5), 119.86 (C-20), 121.54 (C-3), 123.90 (C-60), 126.77 (C-6),
129.49 (C-4a), 131.72 (C-70), 136.12 (C-4), 140.24 (C-8a), 140.37 (C-30), 149.13
(C-2), 154.50 (C-8).
7-(1,5-Dimethyl-1-vinyl-4-hexen-1-yl)-8-quinolinol (20). Method A: A
stirred solution of ether 10 (1.0 g, 3.5 mmol) in chlorobenzene (21 mL) was refluxed
for 40 h. After cooling, the solvent was evaporated in vacuum, and the residue was
purified by column chromatography (hexane–EtOAc 5:1). Yield: 0.34 g (34%); green
oil; Rf ¼ 0.77 (hexane–EtOAc 5:1).
Method B: Ether (1.0 g, 3.5 mmol) was heated at 160 ꢀC for 8 h. After cooling
the reaction mixture was subjected to column chromatography (hexane–EtOAc 5:1).
Yield: 0.61 g (61%). IR (film): 3330 (OH), 1573, 1502, 1450, 1366, 1280, 1220,
1
1099 cmꢂ1. H NMR (CDCl3): 1.50 (s, 3H, CH3), 1.60 (s, 3H, CH3), 1.62 (s, 3H,
0
0
0
CH3), 1.79 (m, 1H, C3 -H), 1.87 (m, 01H, C3 -H), 1.98 (m, 1H, C2 -H), 2.24 (m,
0
00
00
1H, C2 -H), 5.10 (m, 3H, C2 -H and C4 -H), 6.39 (m, 1H, C1 -H), 7.32 (d, J ¼ 8.7 Hz,
1H, C5-H), 7.45 (dd, J ¼ 8 and 3.5 Hz, C3-H), 7.55 (d, J ¼ 8.7 Hz, C6-H), 8.22 (d,
J ¼ 8.2 Hz, 1H, C4-H), 8.77 (d, J ¼ 3.5 Hz, C2-H), 9.1 (br. s, 1H, OH). 13C NMR
(CDCl3): 17.55 (CH3), 23.70 (C-30), 23.84 (CH3), 25.65 (CH3), 38.92 (C-20), 44.46
(C-10), 111.61 (C-2’’), 116.80 (C-5), 120.98 (C-3), 124.82 (C-40), 127.15 (C-4a),
128.62 (C-6), 129.66 (C-7), 131.15 (C-50), 136.95 (C-8a), 137.40 (C-4), 146.13
(C-1’’), 146.48 (C-2), 149.13 (C-8). Anal. calcd. for C19H23NO: C, 81.10; H, 8.24;
N, 4.98. Found: C, 81.21; H, 8.44; N, 4.71.
3,3,3’-Trimethyl-3’H-spiro[cyclohexane-1,2’-furo[3,2-h] quinoline] (23
and 24). A mixture of compound 20 (1.14 g, 4 mmol) and H2SO4 (0.45 mL) was
heated at 100 ꢀC for 1 h. After cooling, the reaction mixture was poured into water,
basified with 1 N NaOH, and then extracted with chloroform. The organic layer was
washed with water, dried (MgSO4), and evaporated in vacuo. The residue was
purified by preparative thin-layer chromatography (TLC) to yield 0.42 g (37%)
yellow oil (a 3:2 mixture of diastereomers); Rf ¼ 0.34 (hexane–EtOAc 5:1). A small
amount of this mixture was separated by preparative HPLC and analyzed.
1
cis-Isomer (23): tR ¼ 31 min. IR (film): 1501, 1459, 1376, 1259, 1105 cmꢂ1. H
NMR (CDCl3): 0.97 (s, 3H, CH3), 1.26 (m, 1H, C4-H), 1.27 (d, J ¼ 7 Hz, 3H,

REARRANGEMENT OF ARYL GERANYL ETHERS
3197
CH3), 1.31 (s, 3H, CH3), 1.43 (m, 1H, C2-H), 1.48 (m, 1H, C6-H), 1.55 (m, 2H, C4-H
and C5-H), 1.79 (d, J ¼ 14 Hz, 1H, C2-H), 2.04 (d, J ¼ 13 Hz, 1H, C6-H), 2.14 (m, 1H,
0
0
0
C5-H), 3.29 (q, J ¼ 7 Hz, 1H, C3 -H), 7.33 (m, 1H, C5 -H), 7.34 (m, 1H, C7 -H), 7.37
0
0
(d, JAB ¼ 8.3 Hz, 1H, C4 -H), 8.15 (d, J ¼ 8.2 Hz, 1H, C6 -H), 8.91 (d, J ¼ 2.6 Hz, 1H,
C8 -H). 13C NMR (CDCl3): 15.26 (CH3), 19.33 (C-5), 27.71 (CH3), 31.10 (C-3), 33.80
0
(CH3), 37.14 (C-6), 39.18 (C-4), 42.28 (C-2), 47.40 (C-30), 93.48 (C-1), 119.30 (C-50),
120.39 (C-70), 123.66 (C-40), 129.07 (C-50a), 132.11 (C-30aþ), 134.11 (C-90a),þ137.95
(C-60), 148.57 (C-80), 152.49 (C-90b). MS (m=z): 281 (M , 92%), 266 (M -CH3,
83), 238 (Mþ- C3H7, 18), 210 (Mþ- C5H11, 80), 172(100), 158 (76). Anal. calcd. for
C19H23NO: C, 81.10; H, 8.24; N, 4.98. Found: C, 80.82; H, 8.40; N, 4.70.
trans-Isomer (24): tR ¼ 33 min. IR (film): 1512, 1457, 1361, 1264, 1084 cmꢂ1. 1H
NMR (CDCl3): 0.94 (s, 3H, CH3), 1.25 (m, 1H, C4-H), 1.26 (s, 3H, CH3), 1.27 (d,
J ¼ 7 Hz, 3H, CH3), 1.41 (d, J ¼ 14 Hz, 1H, C2-H), 1.51 (m, 1H, C6-H), 1.53 (m,
1H, C4-H), 1.60 (m, 1H, C5-H), 1.87 (d, J ¼ 14 Hz, 1H, C2-H), 2.04 (m, 1H, C6-
0
0
H), 2.13 (m, 1H, C5-H), 3.26 (q, J ¼ 7 Hz, 1H, C3 -H), 7.33 (m, 1H, C5 -H), 7.34
0
0
0
(m, 1H, C7 -H), 7.36 (d, JAB ¼ 10 Hz, 1H, C4 -H), 8.13 (d, J ¼ 8 Hz, 1H, C6 -H),
8.90 (d, J ¼ 3 Hz, 1H, C8 -H). 13C NMR (CDCl3): 15.38 (CH3), 19.19 (C-5), 28.07
0
(CH3), 30.93 (C-6), 31.52 (C-3), 33.07 (CH3), 39.08 (C-4), 47.23 (C-30), 49.21
(C-2), 93.03 (C-1), 119.21 (C-50), 120.47 (C-70), 123.32 (C-40), 129.03 (C-50a),
131.12 (C-30a), 135.30 (C-90a), 136.84 (C-60), 149.11 (C-80), 152.92 (C-90b). MS
(m=z): 281 (Mþ, 94%), 266 (Mþ-CH3, 80), 238 (Mþ-C3H7, 21), 210 (Mþ-C5H11,
76), 172 (100), 158 (78). Anal. calcd. for C19H23NO: C, 81.10; H, 8.24; N, 4.98.
Found: C, 80.91; H, 8.52; N, 4.73.
8-[(2,6,6-Trimethyl-2-cyclohexen-1-yl)methoxy]quinoline
(25). PTSA
(2.22 g, 11.7 mmol), was added to a solution of ether 19 (1.66 g, 5.85 mmol) in toluene
(30 mL) and the resulting mixture was stirred at rt for 40 h. The reaction mixture was
washed with water and dried (MgSO4), and the solvent was evaporated under reduced
pressure. The residue was purified by column chromatography (hexane–EtOAc 5:1)
to afford 0.6 g (36%) yellow oil. Rf ¼ 0.56 (hexane–EtOAc 4:1). IR (film): 1670,
1
1597, 1569, 1500, 1467, 1376, 1259, 1105 cmꢂ1. H NMR (CDCl3): 1.03 (s, 3H,
0
0
CH3), 1.05 (s, 3H, CH3), 1.25 (m, 1H, C5 -H),0 1.54 (m, 1H, C5 -H), 1.85 (s, 3H,
0
CH3), 2.11 (br s, 2H, C4 -H),02.51 (br s, 1H, C1 -H), 4.12 (m, 1H, OCH2), 4.21 (m,
1H, OCH2), 5.50 (br s, 1H, C3 -H), 7.12 (d, J ¼ 7.7 Hz, 1H, C7-H), 7.41 (d, J ¼ 8.2 Hz,
Hz, 1H, C5-H), 7.49 (m, 1H, C3-H), 7.50 (m, 1H, C6-H), 8.22 (d, J ¼ 8.0 Hz, 1H, C4-
13
H), 9.04 (d, J ¼ 2.9 Hz, 1H, C2-H). C NMR (CDCl3): 23.09 (C-40), 23.30 (CH3),
26.87 (CH3), 27.14 (CH3), 31.90 (C-60), 31.94 (C-50), 48.72 (C-10), 69.85 (OCH2),
109.43 (C-7), 119.25 (C-5), 121.50 (C-3), 123.04 (C-30), 127.35 (C-6), 129.60 (C-4a),
133.19 (C-20), 137.38 (C-4), 138.74 (C-8a), 148.44 (C-2), 154.18 (C-8). MS (m=z):
281 (Mþ, 10%), 280 (Mþ-1, 32), 158 (Mþ-C9H15, 28), 145 (Mþ-C10H16, 100). Anal.
calcd. for C19H23NO: C, 81.10; H, 8.24; N, 4.98. Found: C, 81.01; H, 8.47; N, 4.81.
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}
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