Convenient formation of six- to nine-membered carbocyclic rings by 2-pyridyl radical cyclization: A generalized synthesis of pyridine-fused linear tricyclic systems

Article abstract of DOI:10.1055/s-2005-916034

Intramolecular cyclization of 2-pyridyl radicals derived from 2-bromopyridin-3-yl substituted methylenecycloalkanes 19-22, vinylcycloalkanols 23 and 24, allylcycloalkanols 26-28, and butenylcycloalkanols 32-34 proceed via 6-, 7-, 8-, and 9-endo-trig pathw

Full text of DOI:10.1055/s-2005-916034

PAPER
3067
Convenient Formation of Six- to Nine-Membered Carbocyclic Rings by
2-Pyridyl Radical Cyclization: A Generalized Synthesis of Pyridine-Fused
Linear Tricyclic Systems
Synthesis of
P
a
yridine-Fus
r
e
d
L
inea
b
r
T
ricyclic
S
e
ystem
s
ndu Maiti,a Michael G. B. Drew,b Ranjan Mukhopadhyay,a Basudeb Achari,a Asish Kr. Banerjee*a
a
Medicinal Chemistry Division, Indian Institute of Chemical Biology, 4 Raja S. C. Mullick Road, Kolkata 700 032, India
Fax +91(33)24735197; E-mail: ashisbanerjee@iicb.res.in
Department of Chemistry, University of Reading, Whiteknights, Reading RG6 6AD, UK
Fax +44(118)3786331; E-mail: m.g.b.drew@reading.ac.uk
b
Received 17 May 2005
H
Abstract: Intramolecular cyclization of 2-pyridyl radicals derived
from 2-bromopyridin-3-yl substituted methylenecycloalkanes 19–
22, vinylcycloalkanols 23 and 24, allylcycloalkanols 26–28, and
butenylcycloalkanols 32–34 proceed via 6-, 7-, 8-, and 9-endo-trig
pathways, giving six-, seven-, eight-, and nine-membered ring an-
nulated pyridines respectively. However, the vinyl cyclopentanol
25 produced only the 6-exo-cyclized product 46, while the substitut-
ed allylcyclohexanol 29 and the butenylcyclohexanol 31 failed to
cyclize, producing only the double bond isomerized debrominated
olefins. Thus the method provides a useful entry to diverse classes
of fused pyridines, with the ring size of the cycloalkane and the
presence of additional substituents in the ring playing an important
role in determining the outcome of the reactions.
TBTH
AIBN
N
N
N
Br
1
H
3 (90%)
H
H
TBTH
AIBN
OH
OH
OH
N
Br
H
4 (78%)
2
H
H
TBTH
AIBN
+
N
OH
N
N
Br
OH
Me
7 (55%)
Key words: TBTH, 2-pyridyl radical cyclization, pyridine-fused
tricyclic systems, endo-selective radical cyclization
6 (34%)
5
Scheme 1
strates differing in substitution pattern (either at the ring
juncture or in other ring positions). In this paper we report
in detail the scope of this strategy for the synthesis of six-
to nine-membered linear carbocyclic ring annulated pyri-
dine derivatives.
Organotin-mediated intramolecular radical cyclization re-
actions provide a simple synthetic entry for the construc-
tion of various cyclic compounds.1,2 Radical reactions
have also been extended successfully to some heterocy-
clic systems, e.g. thiophene, indole,3 but the feasibility of
such reactions utilizing pyridyl radicals4 to generate pyri-
dine-fused ring systems has been explored only to a very
limited extent. We have previously demonstrated5
(Scheme 1) that 2-pyridyl radicals derived via Bu3SnH
(TBTH) treatment of 2-bromopyridinyl substituted meth-
ylenecyclohexane 1 and allylcyclohexanol 2 undergo ex-
clusive endo-selective cyclizations to give six- and eight-
membered ring annulated pyridines 3 and 4 in excellent
yields. However, cyclization of the 2-bromopyridinyl
substituted vinylcyclohexanol 5, unlike that of the compa-
rable aryl radicals,2d,f afforded the 6-exo product 6 in sig-
nificant amounts besides the expected 7-endo compound
7 as the major component.
In order to bring out the dependence of the process on the
ring size of the cycloalkane, the substrates selected were
the methylenecyclopentyl and -cycloheptyl analogues of
1, the cyclopentanol and cycloheptanol analogues of 2,
and the cyclopentanol analogue of 5 (cycloheptanol ana-
logue could not be synthesized). Butenylcycloalkanol
substrates, not included in the earlier study, were also in-
vestigated. Additionally, the influence of a gem-dimethyl
or a quaternary methyl substituent in the cyclohexane ring
on the regio- and stereochemical outcome of the cycliza-
tion process was explored using several olefins. The sub-
strates were prepared through the intermediacy of some
ketones.
It therefore appeared that cyclizations involving 2-pyridyl
radicals, which differ somewhat from those of the aryl an-
alogues, may offer a convenient route to various pyridine-
fused heterocycles, provided a detailed investigation is
carried out to determine the feasibility of the method to
synthesize products varying in ring sizes, and using sub-
Preparation of Ketones
2-Bromo-3-(bromomethyl)pyridine5 (8) was reacted with
the enol acetate 9 to obtain ketone 10 (Scheme 2). Using
8 for alkylation of the methyl analogue6 11 of Hage-
mann’s ester followed by hydrolytic decarboxylation of
the alkylated product 12 to 13 and conjugate addition of a
methyl group following a standard procedure7 furnished
the gem dimethyl substituted ketone 14 (Scheme 3).
SYNTHESIS 2005, No. 18, pp 3067–3078
x
x.
x
x
.
2
0
0
5
Advanced online publication: 29.09.2005
DOI: 10.1055/s-2005-916034; Art ID: P06705SS
© Georg Thieme Verlag Stuttgart · New York

3068
S. Maiti et al.
PAPER
Alkylation of the enamines 15 and 16 with 8 afforded the Since the condensation of 17 with vinyllithium produced
ketones 17 and 18 (Scheme 4).
a mixture of products, use was made of vinylmagnesium
bromide in THF, which furnished 25 in very good yield
(Scheme 6). On the other hand, vinylation of 18 could not
be achieved with vinyllithium, vinylmagnesium bromide
or other reagents.
OCOCH3
Me
Me
Br
a
+
N
Br
O
N
Br
10
8
9
Me
Me
Scheme 2 Reagents and conditions: (a) MeLi, bipyridyl, DME,
–5 °C, 1.5 h, 40%.
a
OH
OH
O
N
Br
N
Br
10
23 (82%)
O
O
Me
Me
Me
H
Me
b
a
8
+
Me
a
CO2Me
Me
N
Me
12
Br
O
N
Br
N
N
Br
CO2Me
11
24 (85%)
14
O
H
Me
b
c
O
OH
Br
N
Br
O
N
Me
N
Br
Br
25 (76%)
17
14
13
Scheme 6 Reagents and conditions: (a) Bu3SnCH=CH2, MeLi,
–78 °C, 3 h; (b) CH2=CHCH2Br, Mg, THF, 0 °C to r.t., 4 h.
Scheme 3 Reagents and conditions: (a) t-BuOK, THF, –10 °C to
r.t., 24 h, 70%; (b) LiCl, DMSO, 160 °C, 8 h, 65%; (c) MeLi, CuI,
BF3·Et2O, –50 °C, 3 h, 85%.
The stereochemistry of 23 and 24 were established from
the X-ray crystallographic structure of the cyclized prod-
ucts. The stereochemistry of the remaining member 25
was assigned by analogy.2g,8
N
a
( )n
+
8
( )n
O
N
Br
15 (n = 1)
16 (n = 3)
17 (n = 1, 70%)
18 (n = 3, 40%)
Synthesis of Allylcycloalkanols
Allylcycloalkanols 26–29 were prepared by condensation
of allylmagnesium bromide with the ketones 10, 14, 17,
and 18 in THF (Scheme 7). The stereochemistries of 26–
28 were determined by analogy.2g The cis stereochemistry
of 29 was assigned by comparing the NMR spectral data
with that of the corresponding vinyl alcohol 23.
Scheme 4 Reagents and conditions: (a) NaI, EtOH, r.t., 24 h.
Synthesis of Methylenecycloalkane Derivatives
The exo methylene compounds 19–22 were synthesized
by Wittig olefination of the ketones 10, 14, 17, and 18, re-
spectively, using the standard procedure (Scheme 5).
R
R
R
R
H
a
R2
( )n
R2
( )n
R2
R2
R1
R1
O
OH
N
N
Br
Br
a
( )n
( )n
14: R = Me; n = 2
17: R = H; n = 1
18: R = H; n = 3
O
N
26: R = Me; n = 2 (80%)
27: R = H; n = 1 (78%)
28: R = H; n = 3 (82%)
N
Br
Br
10: R1 = Me, R2 = H, n = 2
14: R1 = H, R2 = Me, n = 2
17: R1 = R2 = H, n = 1
18: R1 = R2 = H, n = 3
19: R1 = Me, R2 = H, n = 2, 88%
20: R1 = H, R2 = Me, n = 2, 90%
21: R1 = R2 = H, n = 1, 92%
22: R1 = R2 = H, n = 3, 90%
Me
Me
a
OH
O
N
N
Br
Br
Scheme 5 Reagents and conditions: MePPh3I, t-BuOK, toluene,
0 °C to r.t., 4 h.
10
29 (55%)
Scheme 7 Reagents and conditions: (a) CH2=CH-CH2Br, Mg,
THF, 0 °C to r.t., 4 h.
Synthesis of Vinylcycloalkanols
The vinyl cycloalkanols 23 and 24 were prepared by con-
densation of the ketones 10 and 14 with vinyllithium.
Synthesis 2005, No. 18, 3067–3078 © Thieme Stuttgart · New York

PAPER
Synthesis of Pyridine-Fused Linear Tricyclic Systems
3069
of 37 is shown in Figure 1 (top) together with the atomic
numbering scheme. There is also a water molecule in the
Synthesis of Butenylcycloalkanols
For the preparation of the butenyl alcohols, the cycloal- asymmetric unit which forms intermolecular hydrogen
kanones 10, 14, 17, 18 and 305 needed to be condensed bonds to three distinct molecules involving N(2) at 2.87Å,
with butenylmagnesium bromide in THF (Scheme 8). The O(13) (–x, –y, –z) at 2.80Å and O(13) (0.5–x, –0.5+y, –z)
butenyl alcohols 33 and 34 were indeed smoothly ob- at 2.85Å. In the asymmetric unit of 39, there are two mol-
tained as a single diastereomer each by the Grignard reac- ecules with similar conformations. One is shown in
tions of butenyl bromide with the cycloalkanones 30 and Figure 1 (bottom) with atomic numbering scheme. There
18. In contrast, the reaction with 14 or 17 took place only are intermolecular hydrogen bonds connecting the two
in the presence of CeCl3, providing the desired alcohol 31 molecules A and B, N(2B)….O(13A) 2.88Å and
or 32 in excellent yield. No butenyl alcohol could howev- N(2A)….O(13B) (x, 1+y, z) 2.95Å.
er be prepared from 10, perhaps due to steric crowding by
the angular methyl group.
Me
Me
+
23
R
R
R
R
N
OH
H
N
OH
Me
a
( )n
( )n
37 (74%)
38 (16%)
O
OH
N
N
Br
Br
Me
Me
H
Me
14: R = Me, n = 2
17: R = H, n = 1
31: R = Me, n = 2, 75%
32: R = H, n = 1, 74%
H
Me
+
H
24
N
b
OH
N
OH
Me
( )n
( )n
OH
O
N
N
Br
Br
39 (75%)
40 (20%)
30: n = 1
18: n = 2
33: n = 1 (70%)
34: n = 2 (61%)
Scheme 10
Scheme 8 Reagents and conditions: (a) CH2=CHCH2CH2Br, Mg,
CeCl3, THF, r.t., 24 h; (b) CH2=CHCH2CH2Br, Mg, THF, 0 °C, 4 h.
Me
Me
H
Me
OH
Me
42 (51%)
29
26
The H/OH trans relationship in the alcohol 33 was de-
duced from the ring junction stereochemistry established
for the cyclization product 50. This relationship was as-
sumed for the other butenylcycloalkanols also.
OH ;
N
N
41 (65%)
Scheme 11
Me
Me
OH
Cyclization Studies
H
All the cyclization reactions were carried out with TBTH
and a catalytic amount of AIBN in refluxing benzene un-
der high dilution. Schemes 9 to 15 describe the results.
The new compounds have been fully characterized by el-
31
N
1
Me
43 (51%)
emental and spectral analyses including MS as also H
and 13C NMR as mentioned in the experimental section.
Wherever necessary and feasible, X-ray crystallographic
analysis has been carried out. The following points may,
however, be particularly noted.
Scheme 12
The ring junction stereochemistry of the cyclized products
38, 40 (Scheme 10), and 46 (Scheme 13) were assumed to
be trans as the corresponding centers of the starting ole-
fins are unlikely to be involved in the radical cyclization
reaction. The stereochemical assignments for the benzylic
methyl groups in these compounds have based on the ob-
servation that the protons resonate at downfield positions
(d = 1.44–1.53) in the 1H NMR spectra comparable to that
reported9 for similar benzodecalin derivatives (d = 1.31–
1.32, d = 1.10 for the epimer).
Me
Me
H
Me
19
20
;
N
N
H
H
35 (90%)
36 (90%)
Scheme 9
X-ray crystallographic investigation established the struc-
ture and stereochemistry of 37 and 39 (Scheme 10). That
Synthesis 2005, No. 18, 3067–3078 © Thieme Stuttgart · New York

3070
S. Maiti et al.
PAPER
H
H
21, 22
25
;
( )n
N
N
H
OH
Me
44 (n = 1, 90%)
45 (n = 3, 90%)
46 (65%)
Scheme 13
H
( )n
27, 28
OH
N
47: n = 1 (70%)
48: n = 3 (65%)
Scheme 14
Figure 2 The X-ray crystal structure of 50.
chemical shifts of some of the methylene groups due to gg
effect.
Effect of Variation in Olefin Chain Length
Our earlier study has shown that for olefins extending by
1–3 carbon atoms from the cyclohexane ring, endo-trig
cyclization is the exclusive or predominant mode of reac-
tion. The present study using a butenyl carrying substrate
33 demonstrates that the same trend persists with a longer
chain also (Scheme 15).
H
( )n
OH
32, 33
N
49: n = 1 (35%)
50: n = 2 (61%)
H
H
OH
+
OH
34
N
N
Figure 1 X-ray structure of 37 (top) and X-ray structure of 39
(bottom).
51 (30%)
52 (17%)
Scheme 15
The structure and trans geometry of the ring junction of
50 (Scheme 15) was also established through an X-ray
crystallographic study (shown in Figure 2 together with
the atomic numbering scheme). The molecules are held
together in the unit cell by intermolecular hydrogen bonds
between N(2) and O(13) (–x, 0.5+y, 0.5–z) at 3.20Å. Un-
fortunately, X-ray analysis of 49, 51, and 52 failed be-
cause the crystals obtained from repeated trials were
found to diffract weakly. From the similarity of 1H NMR
pattern, the ring junction stereochemistry of 49 and 51
were deduced to be the same (trans) as in 50. By compar-
ing the 13C NMR values of 51 and 52, the cis ring junction
for 52 has been proposed mainly based on the premise that
this isomer is expected to have lower values for the carbon
Effect of Variation in Substitution Pattern
Radical cyclization of the methyl substituted analogue 19
of 1 furnished only the corresponding 6-endo cyclized
product 35 with trans ring junction. The gem-dimethyl
substituted alkene 20 also followed the 6-endo-cycliza-
tion route, but produced an inseparable diastereomeric
mixture (4:1) of the cyclized products 36 (Scheme 9). The
predominant preference for endo cyclization mode in the
unsubstituted substrate 1 → 3 is therefore applicable also
to substituted ones. Extending the comparison to sub-
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PAPER
Synthesis of Pyridine-Fused Linear Tricyclic Systems
3071
strates carrying a vinyl or allyl substituent (e.g., 23, 24 vs In conclusion, Bu3SnH-mediated radical cyclization of 3-
5; 26, 29 vs 2) showed 29 to be the sole exception. In this substituted 2-pyridyl radicals follows, in general, the
case the cis disposition of the ring forming termini cou- endo-trig pathway, generating six- to nine-membered ring
pled with the availability of an allyl hydrogen appears to annulated pyridines in good yields. The exo-trig cycliza-
facilitate 1,6 H shift10 leading to the double bond isomer- tion mode is preferred only in case of the vinylcyclopen-
ized product 42 (Scheme 16). For the next higher homo- tanol derivative 25. Presence of additional substituents at
logue (butenyl carrying), only one substituted substrate 31 the ring juncture or next to it may disfavor the cyclization
could be prepared and tested. In this case, even though the when eight- or nine-membered rings are targets for syn-
reacting termini are trans distributed, steric crowding pos- thesis. In such cases allyl hydrogens appear to be prefer-
sibly interferes with the cyclization process and the allylic entially abstracted by the pyridyl radical leading to double
hydrogen shift seems to be favored to form 43 bond isomerized products. The results suggest that such 2-
(Scheme 12).
pyridyl radical cyclizations do constitute a simple, con-
vergent and general synthetic method for a new series of
pyridine-fused six-, seven-, eight- and nine-membered
ring annulated polycyclic compounds.
Me
Me
29
H
42
OH
OH
N
N
Mps recorded for the compounds are uncorrected. NMR spectra of
the compounds were recorded in CDCl3 solutions with a Bruker
DPX-300 spectrometer. In all cases, chemical shifts are in d (ppm)
relative to TMS as internal standard. Protonation levels of the car-
bons indicated in 13C NMR (75 MHz) data were derived from DEPT
spectra. Mass spectra were recorded using a JEOL AX-500 mass
spectrometer. IR spectra were recorded using a JASCO FT/IR-410
spectrometer. All reagents were of commercial grade and used from
freshly opened containers without purification. Organic solvents
were dried by standard methods and distilled before use. All the re-
actions were performed under N2. Reaction progress was monitored
by TLC on precoated aluminum-backed plates (Merck Kieselgel
60F254) and the spots were visualized by UV light. Anhyd Na2SO4
was used as drying agent during extraction processes. Silica gel
(60–120/100–200/230–400 mesh) was used for column chromatog-
raphy. Petroleum ether used was of boiling range 60–80 °C.
Scheme 16
Effect of Variation in the Ring Size of the Cyclo-
alkane Moiety
The effect of variation in ring size of the cycloalkanyl
component could also be tested. For the methylenecy-
cloalkane series, radical cyclization of 21 and 22 pro-
duced the respective 6-endo products 44 and 45 as with
their cyclohexane analogue 2. The only difference with
the latter is that the products are obtained as inseparable Bu3SnH (1 M solution in hexane) was purchased from Aldrich.
diastereomeric mixtures in ratios of 1:1 and 2:3 rather
2-(2-Bromopyridin-3-ylmethyl)-2-methylcyclohexanone (10)
than as a single isomer. Though the vinylcycloheptanol
A solution of MeLi (15.9 mL of 1 M solution in Et2O) was added to
derivative remained elusive, the cyclopentanol derivative
a solution of bipyridyl (4 mg, 0.03 mmol) in DME (25 mL) at –5 °C.
25 could be prepared. Its cyclization gave only the 6-exo
An aliquot of 9 (1.23 g, 7.97 mmol) was added to the solution with
stirring over 30–40 min11 and 8 (2 g, 7.97 mmol) was then added
product 46 (Scheme 13), unlike 5 which formed mainly
the 7-endo product 7. Radical cyclization of each of the al-
rapidly. The mixture was further stirred for 30 min and then decom-
lyl alcohols 27 and 28 afforded the respective 8-endo posed with aq sat. NaHCO3 solution. The solvent was removed, and
the aqueous part was extracted with Et2O (3 × 50 mL). The com-
bined organic layers were washed with brine, dried and evaporated.
The crude material on chromatography gave 10 as a colorless oil
(900 mg, 40%).
products 47 and 48 in good yield (Scheme 14). This be-
havior parallels our earlier observation5 on the corre-
sponding cyclohexanol substrate.
For the butenyl carrying substrates, cyclization was endo-
selective (Scheme 15) for both cyclopentane and cyclo-
hexane derivatives 32, 33, though the yields were decid-
edly better for the latter. Endo selectivity was also
encountered with the cycloheptane substrate 34, but the
formation of a cis ring-fused product was a surprise. The
unusual formation of the cis product 52 possibly results
from a facile 1,5 hydrogen transfer10 in the intermediate
cyclized radical I to generate II (Scheme 17).
IR (neat): 3045, 2935, 1704, 1577, 1556, 1449, 813 cm–1.
1H NMR: d = 1.18 (3 H, s), 1.67–1.79 (4 H, m), 1.89–1.95 (2 H, m),
2.41–2.59 (2 H, m), 3.14 (2 H, s), 8.21 (1 H, dd, J = 1.9, 4.6 Hz),
7.59 (1 H, dd, J = 1.8, 7.6 Hz), 7.17 (1 H, dd, J = 4.6, 7.6 Hz).
13C NMR: d = 21.0 (CH2), 23.1 (CH3), 27.1 (CH2), 38.4 (CH2), 38.7
(CH2), 40.8 (CH2), 50.3 (C), 122.4 (CH), 136.7 (C), 140.4 (CH),
146.0 (C), 147.8 (CH), 214.7 (C=O).
MS (EI): m/z = 284 (M+ + 1 for 81Br), 282 (M+ + 1 for 79Br), 202
(100%), 158, 144, 130, 120.
Anal. Calcd for C13H16BrNO: C, 55.33; H, 5.72; N, 4.96. Found: C,
55.54; H, 5.58; N, 4.78.
H
3-(2-Bromopyridin-3-ylmethyl)-2-methyl-4-oxocyclohex-2-ene-
carboxylic Acid Methyl Ester (12)
To a stirred solution of t-BuOK (1.92 g, 17.1 mmol) in THF (15
mL), was added the methyl analogue 11 of Hagemann’s ester (2.21
g, 13.15 mmol) in THF (25 mL) at –10 °C and stirred for 45 min.12
To this solution was added 8 (3 g, 11.95 mmol) and NaI (0.6 g, 4
OH
OH
34
N
N
I
II
Scheme 17
Synthesis 2005, No. 18, 3067–3078 © Thieme Stuttgart · New York

3072
S. Maiti et al.
PAPER
mmol) and the mixture was stirred for 2 h. It was then allowed to
reach r.t. and stirred overnight. Aq sat. NH4Cl solution (50 mL) was
added to the mixture and the organic solvent was removed. The
aqueous part was extracted with CH2Cl2 (3 × 60 mL) and the com-
bined organic layers were washed with brine, dried and evaporated.
The crude material on chromatography yielded 12 as a colorless oil
(2.83 g, 70%).
Anal. Calcd for C14H18BrNO: C, 56.77; H, 6.13; N, 4.73. Found: C,
56.54; H, 6.25; N, 4.88.
2-(2-Bromopyridin-3-ylmethyl)cyclopentanone (17)
Prepared by the reported procedure.5
Colorless liquid; yield: 70%.
IR (neat): 2960, 2873, 1737, 1557, 1404, 1155, 801 cm–1.
IR (neat): 3044, 2952, 1731, 1667, 1558, 1434, 1050 cm–1.
1H NMR: d = 1.55–1.65 (1 H, m), 1.77–1.83 (1 H, m), 2.01–2.21 (3
H, m), 2.34–2.43 (1 H, m), 2.48–2.57 (1 H, m), 2.66 (1 H, dd,
J = 8.8, 14.0 Hz), 3.27 (1 H, dd, J = 4.9, 7.1 Hz), 7.20 (1 H, dd,
J = 4.7, 7.5 Hz), 7.54 (1 H, dd, 1.7, 7.5 Hz), 8.24 (1 H, dd, J = 1.7,
4.6 Hz).
13C NMR: d = 20.4 (CH2), 29.2 (CH2), 34.7 (CH2), 37.7 (CH2), 49.0
(CH), 122.7 (CH), 136.8 (C), 139.1 (CH), 144.3 (C), 147.9 (CH),
219.0 (C=O).
1H NMR: d = 1.91 (3 H, s), 2.29–2.41 (2 H, m), 2.43–2.52 (1 H, m),
2.56–2.68 (1 H, m), 3.42 (1 H, t, J = 4.5 Hz), 3.64 and 3.88 (2 H,
2 d, J = 16.8 Hz), 3.79 (3 H, s), 7.15 (1 H, dd, J = 4.7, 7.6 Hz), 7.30
(1 H, br d, J = 6.7 Hz), 8.19 (1 H, dd, J = 1.6, 4.5 Hz).
13C NMR: d = 21.2 (CH3), 25.6 (CH2), 30.5 (CH2), 34.2 (CH2), 52.5
(CH3), 47.5 (CH), 123.0 (CH), 134.3 (C), 136.1 (C), 136.7 (CH),
144.4 (C), 147.4 (CH), 153.9 (C), 172.3 (CO), 196.6 (C=O).
MS (EI): m/z = 339 (M+ for 81Br), 337 (M+ for 79Br), 280, 258
(100%), 198, 184, 173.
MS (EI): m/z = 256 (M+ + 1 for 81Br), 254 (M+ + 1 for 79Br), 174
(100%), 146, 132, 117.
Anal; Calcd for C15H16BrNO3: C, 53.27; H, 4.77; N, 4.14. Found: C,
53.46; H, 4.89; N, 4.02.
Anal. Calcd for C11H12BrNO: C, 51.99; H, 4.76; N, 5.51. Found: C,
52.23; H, 4.87; N, 5.37.
2-(2-Bromopyridin-3-ylmethyl)-3-methylcyclohex-2-enone (13)
Decarboxylation of 12 using aq LiCl and DMSO13 yielded 13 as a
white solid (2.83 g, 65%); mp 70–71 °C.
IR (KBr): 3047, 2949, 1651, 1628, 1558, 1400, 796 cm–1.
1H NMR: d = 1.89 (3 H, s), 1.99–2.08 (2 H, m), 2.44–2.50 (4 H, m),
3.74 (2 H, s), 7.13 (1 H, dd, J = 7.5, 4.8 Hz), 7.19 (1 H, d, J = 7.5
Hz), 8.17 (1 H, br d, J = 4.5 Hz).
13C NMR: d = 21.8 (CH3), 21.9 (CH2), 30.3 (CH2), 32.9 (CH2), 37.5
(CH2), 122.7 (CH), 132.3 (C), 136.9 (CH), 136.7 (C), 144.3 (C),
147.2 (CH), 159.4 (C), 198.1 (C=O).
2-(2-Bromopyridin-3-ylmethyl)cycloheptanone (18)
The same procedure used for the synthesis of 17 afforded the ketone
18 as a colorless oil; yield: 40%.
IR (neat): 3046, 2925, 2854, 1700, 1577, 1448, 1051 cm–1.
1H NMR: d = 1.26–1.54 (3 H, m), 1.58–1.59 (1 H, m), 1.61–1.75 (1
H, m), 1.84 (3 H, d like), 2.46 (2 H, dd-like), 2.67 (1 H, dd, J = 6.2,
13.6 Hz), 3.06 (1 H, app. q, J = 6.9 Hz), 3.18 (1 H, dd, J = 7.5, 13.6
Hz), 7.17 (1 H, dd, J = 4.7, 7.5 Hz), 7.54 (1 H, dd, J = 1.7, 7.5 Hz),
8.20 (1 H, dd, J = 1.8, 4.6 Hz).
13C NMR: d = 23.7 (CH2), 28.7 (CH2), 28.8 (CH2), 31.2 (CH2), 36.9
(CH2), 43.2 (CH2), 51.0 (CH), 122.6 (CH), 136.9 (C), 139.9 (CH),
144.6 (C), 147.8 (CH), 214.1 (C=O).
MS (EI): m/z = 281 (M+ for 81Br), 279 (M+ for 79Br), 200 (100%),
172, 144, 130, 113, 101.
Anal. Calcd for C13H14BrNO: C, 55.73; H, 5.04; N, 5.00. Found: C,
55.91; H, 4.90; N, 5.15.
MS (EI): m/z = 284 (M+ + 1 for 81Br), 282 (M+ + 1 for 79Br), 240,
238, 203, 202 (100%), 184, 146, 172, 130, 120.
Anal. Calcd for C13H16BrNO: C, 55.33; H, 5.72; N, 4.96. Found: C,
55.49; H, 5.81; N, 4.83.
2-(2-Bromopyridin-3-ylmethyl)-3,3-dimethylcyclohexanone
(14)
A solution of MeLi (15.5 mL of 1.5 M solution in Et2O) was added
dropwise at –25 °C to a suspension of CuI (4.42 g, 23.2 mmol) in
Et2O (10 mL).7 The resulting yellow suspension was cooled to –50
°C, BF3·OEt2 (1.317 g, 9.28 mmol) was added, and the mixture
stirred for 5 min. The temperature was then allowed to reach –30
°C, and a solution of 13 (0.280 g, 4.64 mmol) in Et2O (5 mL) was
added and the mixture stirred for 30 min. Additional BF3·OEt2
(1.317 g, 9.28 mmol) was added to the mixture. The stirring was
continued for 1 h at –30 °C followed by 1 h at 0 °C. The reaction
was quenched with aq sat. NH4Cl solution (50 mL) at 0 °C. The
aqueous part was extracted with Et2O (3 × 50 mL) and the com-
bined organic layers were washed with brine, dried and evaporated.
The crude material on chromatography afforded 14 as a white solid
(1.168 g, 85%); mp 72 °C.
2-Bromo-3-(1-methyl-2-methylenecyclohexylmethyl)pyridine
(19); Typical Procedure
A suspension of methyltriphenylphosphonium iodide (1.29 g, 3.19
mmol) and t-BuOK (0.36 g, 3.19 mmol) in toluene (15 mL) was
stirred for 2 h at 0 °C.14 A solution of 10 (300 mg, 1.06 mmol) in
toluene (5 mL) was added and the mixture was further stirred for 2
h at 0 °C. It was then decomposed with aq sat. NH4Cl solution. The
solvent was removed and the aqueous part was extracted with Et2O
(3 × 25 mL). The combined organic layers were washed with brine,
dried and evaporated. The crude material on chromatography gave
19 as a white solid (262 mg, 88%); mp 42 °C.
IR (KBr): 3081, 2925, 1634, 1554, 1401, 1188, 897 cm–1.
1H NMR: d = 0.97 (3 H, s), 1.39–1.44 (2 H, m), 1.64–1.80 (4 H, m),
2.32–2.37 (2 H, m), 2.87 (1 H, d, J = 13.8 Hz), 3.14 (1 H, d,
J = 13.7 Hz), 4.46 (1 H, s), 4.80 (1 H, s), 7.12 (1 H, dd, J = 4.8, 7.6
Hz), 7.32 (1 H, dd, J = 1.9, 7.6 Hz), 8.19 (1 H, dd, J = 1.9, 4.6 Hz).
13C NMR: d = 22.6 (CH2), 25.1 (CH3), 28.9 (CH2), 33.8 (CH2), 41.3
(CH2), 41.9 (CH2), 41.9 (C), 109.7 (CH2), 122.3 (CH), 136.8 (C),
140.0 (CH), 146.4 (C), 147.8 (CH), 153.6 (C).
IR (KBr): 3065, 3041, 2936, 1707, 1559, 1436, 1073, 801 cm–1.
1H NMR: d = 0.86 (3 H, s), 1.32 (3 H, s), 1.63–1.64 (1 H, m), 1.75–
1.99 (3 H, m), 2.18–2.30 (2 H, m), 2.74–2.80 (2 H, m), 3.01 (1 H,
dd, J = 11.0, 13.6 Hz), 7.14 (1 H, dd, J = 4.7, 7.5 Hz), 7.83 (1 H,
dd, J = 1.8, 7.6 Hz), 8.16 (1 H, dd, J = 1.9, 4.6 Hz).
13C NMR: d = 20.8 (CH3), 23.4 (CH2), 29.3 (CH2), 29.8 (CH3), 40.4
(CH2), 41.1 (C), 42.2 (CH2), 59.6 (CH), 122.5 (CH), 137.8 (C),
141.5 (CH), 144.0 (C), 147.6 (CH), 211.9 (C=O).
MS (EI): m/z = 281 (M+ for 81Br), 279 (M+ for 79Br), 200 (100%),
173, 171, 109.
MS (EI): m/z = 298 (M+ + 1 for 81Br), 296 (M+ + 1 for 79Br), 217 (M+
Anal. Calcd for C14H18BrN: C, 60.01; H, 6.47; N, 5.00. Found: C,
59.82; H, 6.30; N, 5.16.
+ 1 – Br), 216 (M+ – Br, 100%), 170, 148, 146, 140.
Synthesis 2005, No. 18, 3067–3078 © Thieme Stuttgart · New York

PAPER
Synthesis of Pyridine-Fused Linear Tricyclic Systems
3073
2-Bromo-3-(2,2-dimethyl-6-methylenecyclohexylmethyl)pyri-
dine (20)
Prepared from 14 following the typical procedure for 19; white sol-
id; yield: 90%; mp 59–60 °C.
The combined organic layers were washed with brine, dried and
evaporated. The crude material on chromatography afforded 23 as
a white solid (270 mg, 82%); mp 100–101 °C.
IR (KBr): 3362, 2934, 2862, 1559, 1452, 1051, 804 cm–1.
1H NMR: d = 0.93 (3 H, s), 1.35–1.75 (9 H, m), 2.81 (1 H, d,
J = 13.5 Hz), 2.94 (1 H, d, J = 13.5 Hz), 5.27 (1 H, dd, J = 1.3, 10.9
Hz), 5.41 (1 H, dd, J = 1.3, 17.2 Hz), 6.45 (1 H, dd, J = 10.9, 17.2
Hz), 7.13–7.19 (1 H, m), 7.49 (1 H, dd, J = 1.8, 7.5 Hz), 8.21 (1 H,
dd, J = 1.8, 4.5 Hz).
13C NMR: d = 18.4 (CH3), 21.0 (CH2), 22.3 (CH2), 32.7 (CH2), 35.6
(CH2), 39.4 (CH2), 42.4 (C), 76.4 (C), 113.8 (CH2), 122.0 (CH),
136.5 (C), 140.4 (CH), 141.6 (CH), 146.3 (C), 147.6 (CH).
IR (KBr): 3070, 2940, 2864, 1645, 1556, 1444, 1051 cm–1.
1H NMR: d = 0.99 (3 H, s), 1.06 (3 H, s), 1.38 (1 H, m), 1.52–1.65
(3 H, m), 2.04–2.11 (1 H, m), 2.17–2.27 (2 H, m), 2.71 (1 H, dd,
J = 12.0, 14.1 Hz), 3.05 (1 H, dd, J = 3.3, 14.2 Hz), 4.17 (1 H, s),
4.60 (1 H, s), 7.12 (1 H, dd, J = 4.7, 7.5 Hz), 7.33 (1 H, dd, J = 1.8,
7.5 Hz), 8.16 (1 H, dd, J = 1.9, 4.6 Hz).
13C NMR: d = 23.4 (CH2), 26.7 (CH3), 28.3 (CH3), 32.2 (CH2), 32.7
(CH2), 35.0 (C), 35.9 (CH2), 53.1 (CH), 111.3 (CH2), 122.2 (CH),
138.2 (C), 139.0 (CH), 144.5 (C), 147.0 (C), 147.3 (CH).
MS (EI): m/z = 311 (M+ for 81Br), 309 (M+ for 79Br), 254, 241, 239,
230 (100%), 214, 212, 200, 198, 173, 171, 148, 130, 91.
MS (EI): m/z = 296 (M+ + 1 for 81Br), 295 (M+ for 81Br), 294 (M+ +
1 for 79Br), 293 (M+ for 79Br), 280, 278, 252, 250, 215, 214 (100%),
184, 173, 171, 158, 157, 141, 128.
Anal. Calcd for C15H20BrNO: C, 58.07; H, 6.50; N, 4.51. Found: C,
57.85; H, 6.72; N, 4.35.
Anal. Calcd for C15H20BrN: C, 61.23; H, 6.85; N 4.76. Found: C,
61.39; H, 6.97; N, 4.59.
2-(2-Bromopyridin-3-ylmethyl)-3,3-dimethyl-1-vinylcyclohex-
anol (24)
2-Bromo-3-(2-methylenecyclopentylmethyl)pyridine (21)
Prepared from 17 following the typical procedure for 19; colorless
oil; 92%.
IR (neat): 3066, 2924, 2852, 1636, 1557, 1445, 744 cm–1.
Prepared from 14 following the typical procedure for 23; white sol-
id; yield: 85%; mp 59–60 °C.
IR (KBr): 3360, 3089, 2983, 2937, 2866, 1633, 1560, 1445, 1197,
933, 672 cm–1.
1H NMR: d = 1.31–1.43 (1 H, m), 1.48–1.63 (1 H, m), 1.67–1.96 (2
H, m), 2.40 (2 H, br t, J = 6.6 Hz), 2.59 (1 H, dd, J = 9.6, 13.6 Hz),
2.77 (1 H, s), 3.04 (1 H, dd, J = 5.2, 13.6 Hz), 4.81 (1 H, d, J = 1.9
Hz), 4.95 (1 H, d, J = 1.6 Hz), 7.19 (1 H, dd, J = 4.7, 7.4 Hz), 7.50
(1 H, dd, J = 1.7, 7.5 Hz), 8.20 (1 H, dd, J = 1.9, 4.6 Hz).
13C NMR: d = 24.0 (CH2), 32.4 (CH2), 33.0 (CH2), 40.0 (CH2), 43.4
(CH), 105.5 (CH2), 122.6 (CH), 138.0 (C), 139.1 (CH), 144.6 (C),
147.6 (CH), 155.2 (C).
1H NMR: d = 0.85 (3 H, s), 1.17 (3 H, s), 1.22–1.34 (2 H, m), 1.41–
1.51 (4 H, m), 1.74 (1 H, dd, J = 5.5, 6.5 Hz), 1.78–1.86 (1 H, m),
2.83 (1 H, dd, J = 5.1, 15.6 Hz), 2.96 (1 H, dd, J = 6.8, 15.6 Hz),
4.75 (1 H, d, J = 10.7 Hz), 5.12 (1 H, d, J = 17.2 Hz), 5.52 (1 H, dd,
J = 10.7, 17.2 Hz), 7.15 (1 H, dd, J = 4.6, 7.6 Hz), 7.53 (1 H, dd,
J = 1.3, 7.6 Hz), 8.15 (1 H, dd, J = 1.5, 4.7 Hz).
13C NMR: d = 17.8 (CH3), 22.1 (CH3), 30.9 (CH2), 32.7 (CH2), 34.4
(C), 40.7 (CH2), 42.3 (CH2), 52.4 (CH), 75.7 (C), 110.9 (CH2),
122.5 (CH), 138.6 (CH), 140.2 (C), 144.9 (C), 146.7 (CH), 147.0
(CH).
MS (FAB): m/z = 254 (M+ + 1 for 81Br), 252 (M+ + 1 for 79Br), 196,
176, 172, 154 (100%).
MS (EI): m/z = 325 (M+ for 81Br), 323 (M+ for 79Br), 310, 308, 244,
186, 184 (100%), 173, 171, 162, 140, 91.
Anal. Calcd for C12H14BrN: C, 57.16; H, 5.60; N, 5.55. Found: C,
56.95; H, 5.73; N, 5.64.
Anal. Calcd for C16H22BrNO: C, 59.27; H, 6.84; N, 4.32. Found: C,
59.51; H, 6.97; N, 4.41.
2-Bromo-3-(2-methylenecycloheptylmethyl)pyridine (22)
Prepared from 18 following the typical procedure for 19; colorless
oil; yield: 90%.
IR (KBr): 3066, 2924, 2852, 1636, 1557, 1445, 1051 cm–1.
1H NMR: d = 1.15–1.33 (4 H, m), 1.63–1.82 (2 H, m), 1.88–1.94 (2
H, m), 2.03–2.11 (1 H, m), 2.21–2.28 (1 H, m), 2.63–2.68 (2 H, m),
2.76 (1 H, t, J = 8.2 Hz), 4.38 (1 H, s), 4.74 (1 H, s), 7.16 (1 H, dd,
J = 4.7, 7.4 Hz), 7.36 (1 H, dd, J = 1.7, 7.5 Hz), 8.20 (1 H, dd,
J = 1.8, 4.6 Hz).
13C NMR: d = 26.3 (CH2), 30.6 (CH2), 31.4 (CH2), 33.1 (CH2), 33.8
(CH2), 41.7 (CH2), 45.0 (CH), 113.2 (CH2), 122.2 (CH), 137.7 (C),
139.6 (CH), 144.7 (C), 147.4 (CH), 152.6 (C).
2-(2-Bromopyridin-3-ylmethyl)-1-vinylcyclopentanol (25)
Using an earlier reported procedure,5 25 was prepared as a white
solid; yield: 255 mg (76%); mp 52 °C.
IR (KBr): 3405, 3050, 2957, 1640, 1560, 1446, 917 cm–1.
1H NMR: d = 1.32 (1 H, s), 1.64–1.70 (4 H, m), 1.78–1.94 (2 H, m),
2.04–2.11 (1 H, m), 2.55 (1 H, dd, J = 10.4, 13.5 Hz), 2.93 (1 H, dd,
J = 4.1, 13.6 Hz), 5.14 (1 H, d, J = 10.7 Hz), 5.33 (1 H, d, J = 17.1
Hz), 5.93 (1 H, dd J = 10.8, 17.1 Hz), 7.16 (1 H, dd, J = 4.7, 7.4
Hz), 7.50 (1 H, dd, J = 1.6, 7.5 Hz), 8.20 (1 H, dd, J = 1.7, 4.5 Hz).
13C NMR: d = 21.2 (CH2), 29.3 (CH2), 34.1 (CH2), 41.1 (CH2), 48.3
(CH), 82.6 (C), 112.8 (CH2), 122.6 (CH), 138.5 (C), 139.2 (CH),
143.2 (CH), 144.4 (C), 147.6 (CH).
MS (EI): m/z = 282 (M+ + 1 for 81Br), 280 (M+ + 1 for 79Br), 200
(100%), 173, 171, 118, 109, 91.
MS (EI): m/z = 283 (M+ for 81Br), 281 (M+ for 79Br), 256, 202, 174
(100%), 132, 117, 91.
Anal. Calcd for C14H18BrN: C, 60.01; H, 6.47; N, 5.00. Found: C,
60.25; H, 6.62; N, 4.85.
Anal. Calcd for C13H16BrNO: C, 55.33; H, 5.72; N, 4.96. Found: C,
55.19; H, 5.62; N, 5.12.
2-(2-Bromopyridin-3-ylmethyl)-2-methyl-1-vinylcyclohexanol
(23); Typical Procedure
To a solution of tributylvinylstannane (1.09 g, 3.40 mmol) in anhyd
THF (10 mL) at –45 °C was added a solution of MeLi (3.2 mL of 1
M solution in Et2O), and the mixture was stirred for 30 min, then
cooled down to –78 °C.15 A solution of 10 (300 mg, 1.06 mmol) in
THF (5 mL) was added and the mixture was stirred for 3 h. The re-
action was quenched with aq sat. NH4Cl solution. The solvent was
removed and the aqueous part was extracted with Et2O (3 × 25 mL).
1-Allyl-2-(2-bromopyridin-3-ylmethyl)-3,3-dimethylcyclohex-
anol (26); Typical Procedure
A solution of 14 (300 mg, 1.01 mmol) in THF (10 mL) was added
to a freshly prepared solution of allylmagnesium bromide (from 0.9
mL of allyl bromide and 123 mg of Mg) and stirred for 2 h at 0 °C.
Then the mixture further stirred for 2 h at r.t. It was then quenched
with aq sat. NH4Cl solution. The solvent was removed, and the
Synthesis 2005, No. 18, 3067–3078 © Thieme Stuttgart · New York

3074
S. Maiti et al.
PAPER
IR (KBr): 3409, 2938, 2860, 1635, 1558, 1442, 1048 cm–1.
1H NMR: d = 0.94 (3 H, s), 1.08–1.86 (9 H, m), 2.29 (1 H, dd,
J = 7.1, 13.5 Hz), 2.58 (1 H, dd, J = 7.8, 13.5 Hz), 3.05 (1 H, d,
J = 13.5 Hz), 3.11 (1 H, d, J = 13.5 Hz), 5.21 (2 H, m), 5.87–6.01
(1 H, m), 7.18 (1 H, dd, J = 4.6, 7.5 Hz), 7.93 (1 H, dd, J = 1.9, 7.5
Hz), 8.21 (1 H, dd, J = 1.9, 4.6 Hz).
13C NMR: d = 19.8 (CH3), 20.9 (CH2), 21.3 (CH2), 32.9 (CH2), 33.3
(CH2), 39.6 (CH2), 40.3 (CH2), 42.3 (C), 74.9 (C), 119.5 (CH2),
121.9 (CH), 134.1 (CH), 137.0 (C), 140.7 (CH), 146.4 (C), 147.5
(CH).
aqueous part was extracted with Et2O (3 × 25 mL). The combined
organic layers were washed with brine, dried and evaporated. The
crude material on chromatography yielded 26 as a colorless oil;
yield: 275 mg (80%).
IR (neat): 3421, 3071, 2937, 1559, 1445, 1180, 1052 cm–1.
1H NMR: d = 0.93 (3 H, s), 1.12 (3 H, s), 1.17–1.54 (6 H, m), 1.58–
1.67 (1 H, m), 1.75–1.81 (1 H, m), 1.88 (1 H, dd, J = 6.5, 13.2 Hz),
2.08 (1 H, dd, J = 8.2, 13.4 Hz), 2.76 (1 H, dd, J = 2.9, 16.7 Hz),
3.22 (1 H, dd, J = 6.7, 16.7 Hz), 4.76 (1 H, d, J = 16.8 Hz), 5.04 (1
H, d, J = 9.9 Hz), 5.57–5.71 (1 H, m), 7.21 (1 H, dd, J = 4.6, 7.6
Hz), 7.60 (1 H, d, J = 7.3 Hz), 8.19 (1 H, d, J = 4.3 Hz).
13C NMR: d = 17.7 (CH2), 22.1 (CH3), 30.4 (CH2), 32.7 (CH3), 35.1
(C), 38.3 (CH2), 42.2 (CH2), 47.1 (CH2), 52.7 (CH), 74.1 (C), 119.4
(CH2), 122.7 (CH), 133.2 (CH), 137.9 (CH), 140.8 (C), 144.8 (C),
147.1 (CH).
MS (FAB): m/z (%) = 326 (M+ + 1 for 81Br, 100), 324 (M+ + 1 for
79Br, 100), 306, 282, 284, 244.
Anal. Calcd for C16H22BrNO: C, 59.27; H, 6.84; N, 4.32. Found: C,
59.52; H, 6.75; N, 4.21.
MS (EI): m/z = 339 (M+ for 81Br), 337 (M+ for 79Br), 298 (100%),
296, 252, 184, 148.
2-(2-Bromopyridin-3-ylmethyl)-1-(but-3-enyl)-3,3-dimethyl-
cyclohexanol (31); Typical Procedure
A solution of 14 (180 mg, 0.61 mmol) in THF (5 mL) was added to
dry powdered CeCl3 (from 340 mg of hydrated salt) in ice-cold con-
dition and the mixture was stirred for 1 h at r.t. A solution of bute-
nylmagnesium bromide [prepared from butenyl bromide (0.46 mL)
and Mg (45 mg, 1.85 mg atm) in THF at 0 °C] in THF was added at
0 °C and the mixture was stirred for 4 h and then 24 h at r.t.16 The
reaction was decomposed with aq sat. NH4Cl solution. The solvent
was removed and the aqueous part was extracted with Et2O (3 × 25
mL). The combined organic layers were washed with brine, dried
and evaporated. The crude material on chromatography afforded 31
as a colorless oil; yield: 149 mg (75%).
Anal. Calcd for C17H24BrNO: C, 60.36; H, 7.15; N, 4.14. Found: C,
60.16; H, 7.03; N, 4.27.
1-Allyl-2-(2-bromopyridin-3-ylmethyl)cyclopentanol (27)
Prepared from 17 following the typical procedure for 26; waxy sol-
id; yield: 78%.
IR (KBr): 3337, 3046, 2868, 1638, 1560, 1405, 916 cm–1.
1H NMR: d = 1.43–1.62 (5 H, m), 1.65–1.86 (3 H, m), 1.96–2.29 (1
H, dd, J = 6.7, 13.6 Hz), 2.49 (1 H, dd, J = 8.2, 13.6 Hz), 2.60 (1 H,
dd, J = 10.7, 13.4 Hz), 3.04 (1 H, dd, J = 4.9, 13.9 Hz), 5.20 (2 H,
m), 5.86–6.00 (1 H, m), 7.18 (1 H, dd, J = 4.7, 7.3 Hz), 7.53 (1 H,
dd, J = 1.3, 7.4 Hz), 8.22 (1 H, dd, J = 1.4, 4.7 Hz).
13C NMR: d = 20.9 (CH2), 29.8 (CH2), 34.8 (CH2), 39.3 (CH2), 44.1
(CH2), 47.3 (CH), 81.1 (C), 118.9 (CH2), 122.6 (CH), 134.0 (CH),
138.6 (C), 139.2 (CH), 144.4 (C), 147.5 (CH).
IR (neat): 3429, 3072, 2939, 1640, 1553, 1450, 909 cm–1.
1H NMR: d = 0.95 (3 H, s), 1.10 (3 H, s), 1.22–1.54 (7 H, m), 1.60–
1.82 (4 H, m), 1.93–1.97 (1 H, m), 2.74 (1 H, d, J = 16.3 Hz), 3.18
(1 H, dd, J = 7.2, 16.3 Hz), 4.70–4.81 (2 H, m), 5.41–5.54 (1 H, m),
7.17–7.23 (1 H, m), 7.62 (1 H, d, J = 7.5 Hz), 8.21 (1 H, m).
13C NMR: d = 17.7 (CH2), 22.1 (CH3), 28.2 (CH2), 30.5 (CH2), 32.8
(CH3), 35.0 (C), 37.8 (CH2), 41.8 (CH2), 42.1 (CH2), 52.1 (CH),
74.9 (C), 114.5 (CH2), 122.7 (CH), 137.9 (CH), 138.2 (CH), 140.7
(C), 144.7 (C), 147.1 (CH) (smaller peaks attributed to the minor
isomer are omitted).
MS (FAB): m/z = 298 (M+ + 1 for 81Br, 98%), 296 (M+ + 1 for 79Br,
100%).
Anal. Calcd for C14H18BrNO: C, 56.77; H, 6.13; N, 4.73. Found: C,
56.91; H, 6.25; N, 4.60.
MS (EI): m/z = 353 (M+ for 81Br), 351 (M+ for 79Br), 298, 297, 272
(100%), 252, 226, 186, 184, 172, 162, 140, 106.
1-Allyl-2-(2-bromopyridin-3-ylmethyl)cycloheptanol (28)
Prepared from 18 following the typical procedure for 26; white sol-
id; yield: 82%; mp 56 °C.
IR (KBr): 3380, 3068, 2928, 1636, 1560, 1458, 1190, 781 cm–1.
Anal. Calcd for C18H26BrNO: C, 61.36; H, 7.44; N, 3.98. Found: C,
61.52; H, 7.54; N, 3.85.
1H NMR: d = 1.11–1.19 (1 H, m), 1.29–1.47 (3 H, m), 1.49–1.69 (6
H, m), 1.83–1.97 (2 H, m), 2.41 (1 H, dd, J = 7.5, 13.8 Hz), 2.57–
2.65 (2 H, m), 3.07 (1 H, dd, J = 2.7, 14.2 Hz), 5.14–5.22 (2 H, m),
5.87–6.01 (1 H, m), 7.50 (1 H, dd, J = 1.6, 7.5 Hz), 7.20 (1 H, dd,
J = 4.7, 7.5 Hz), 8.25 (1 H, dd, J = 1.7, 4.6 Hz).
13C NMR: d = 21.9 (CH2), 26.0 (CH2), 27.8 (CH2), 29.2 (CH2), 35.8
(CH2), 39.6 (CH2), 44.4 (CH2), 47.4 (CH), 76.1 (C), 119.3 (CH2),
122.5 (CH), 133.8 (CH), 138.7 (C), 140.2 (CH), 145.0 (C), 147.5
(CH).
2-(2-Bromopyridin-3-ylmethyl)-1-(but-3-enyl)cyclopentanol
(32)
Prepared from 17 following the typical procedure for 31; white sol-
id; yield: 74%; mp 48–49 °C.
IR (KBr): 3395, 2955, 1640, 1561, 1446, 1402, 906 cm–1.
1H NMR: d = 1.32 (1 H, s), 1.48–1.98 (10 H, m), 2.19–2.27 (2 H,
m), 2.57 (1 H, dd, J = 10.5, 13.5 Hz), 4.98 (1 H, d, J = 10.2 Hz),
5.07 (1 H, d, J = 17.1 Hz), 5.82 (1 H, m), 7.18 (1 H, dd, J = 4.7, 7.4
Hz), 7.52 (1 H, dd, J = 1.9, 7.5 Hz), 8.22 (1 H, dd, J = 1.9, 4.6 Hz).
13C NMR: d = 20.8 (CH2), 29.2 (CH2), 29.7 (CH2), 34.8 (CH2), 38.4
(CH2), 38.9 (CH2), 47.8 (CH), 82.3 (C), 114.7 (CH2), 122.7 (CH),
138.6 (C), 139.0 (CH), 139.2 (CH), 144.4 (C), 147.6 (CH).
MS (FAB): m/z (%) = 326 (M+ + 1 for 81Br, 99), 324 (M+ + 1 for
79Br, 100).
Anal. Calcd for C16H22BrNO: C, 59.27; H, 6.84; N, 4.32. Found: C,
59.43; H, 6.94; N, 4.18.
MS (EI): m/z = 311 (M+ for 81Br), 309 (M+ for 79Br), 256, 254, 230
(100%), 202, 200, 186, 184, 173, 171, 148, 130.
1-Allyl-2-(2-bromopyridin-3-ylmethyl)-2-methylcyclohexanol
(29)
Prepared from 10 following the typical procedure for 26; white sol-
id; yield: 55%; mp 94–95 °C.
Anal. Calcd for C15H20BrNO: C, 58.07; H, 6.50; N, 4.51. Found: C,
58.32; H, 6.39; N, 4.65.
Synthesis 2005, No. 18, 3067–3078 © Thieme Stuttgart · New York

PAPER
Synthesis of Pyridine-Fused Linear Tricyclic Systems
3075
2-(2-Bromopyridin-3-ylmethyl)-1-(but-3-enyl)cyclohexanol
(33); Typical Procedure
1H NMR: d = 0.81 (3 H, s), 0.91–2.00 (9 H, m), 2.41–2.60 (3 H, m),
2.87 (1 H, dd, J = 5.3, 17.8 Hz), 7.01 (1 H, dd, J = 4.8, 7.5 Hz), 7.32
(1 H, d, J = 7.5 Hz), 8.35 (1 H, d, J = 4.2 Hz).
13C NMR: d = 15.8 (CH3), 21.9 (CH2), 26.2 (CH2), 28.6 (CH2), 32.3
(C), 36.5 (CH2), 40.3 (CH2), 40.6 (CH), 45.4 (CH2), 120.7 (CH),
131.3 (C), 136.8 (CH), 146.5 (CH), 156.6 (C).
A solution of 305 (160 mg, 0.60 mmol) in THF (4 mL) was added
to a freshly prepared solution of butenylmagnesium bromide17 at
–20 °C, and the mixture was stirred for 4 h at the same temperature.
The reaction was quenched with aq sat. NH4Cl solution. The solvent
was removed and the aqueous part was extracted with Et2O. The
combined organic phases were washed with brine, dried and evap-
orated. The crude material on chromatography gave 33 as a white
solid, yield: 135 mg (70%); mp 84–85 °C.
MS (EI): m/z = 201 (M+, 100%), 186, 172, 159, 144, 130.
Anal. Calcd for C14H19N: C, 83.53; H, 9.51; N, 6.96. Found: C,
83.70; H, 9.43; N, 6.89.
IR (KBr): 3382, 2933, 2853, 1639, 1561, 1406, 747 cm–1.
cis- and trans-6,6-Dimethyl-5,5a,6,7,8,9,9a,10-octahydro-
benzo[g]quinoline (36)
Colorless oil; yield: 90%.
IR (neat): 3054, 2924, 2864, 1581, 1451, 1366, 785 cm–1.
1H NMR: d = 0.90 (3 H, s), 1.00 (3 H, s), 1.04–1.16 (1 H, m), 1.21–
1.40 (2 H, m), 1.46–1.78 (5 H, m), 1.92 (1 H, br d, J = 11.1 Hz),
2.47–2.60 (1 H, m), 2.81 (1 H, dd, J = 5.2, 13.4 Hz), 3.03 (1 H, dd,
J = 5.3, 17.5 Hz), 7.00 (1 H, dd, J = 4.5, 7.4 Hz), 7.35 (1 H, d,
J = 7.6 Hz), 8.3 (1 H, br s).
1H NMR: d = 1.09–1.83 (12 H, m), 2.16–2.31 (2 H, m), 2.51 (1 H,
t, J = 12.3 Hz), 3.15 (1 H, dd, J = 3.2, 13.5 Hz), 4.99 (1 H, d,
J = 10.1 Hz), 5.08 (1 H, d, J = 17.1 Hz), 5.81–5.93 (1 H, m), 7.18
(1 H, dd, J = 4.8, 6.9 Hz), 7.45 (1 H, d, J = 7.2 Hz), 8.22 (1 H, d,
J = 3.9 Hz).
13C NMR: d = 21.6 (CH2), 25.1 (CH2), 26.4 (CH2), 28.0 (CH2), 34.9
(CH2), 36.4 (CH2), 39.6 (CH2), 42.7 (CH), 73.2 (C), 114.7 (CH2),
122.5 (CH), 138.1 (C), 138.8 (CH), 140.0 (CH), 144.6 (C), 147.6
(CH).
13C NMR: d = 20.1 (CH3), 21.5 (CH2), 29.5 (CH2), 30.5 (CH3), 32.7
(C), 33.4 (CH), 34.7 (CH2), 41.0 (CH2), 42.3 (CH2), 46.6 (CH),
120.8 (CH), 132.2 (C), 136.4 (CH), 146.9 (CH), 156.6 (C) (smaller
peaks due to minor isomer are omitted).
MS (EI): m/z = 325 (M+ for 81Br), 323 (M+ for 79Br), 270, 268
(100%), 245, 244, 200, 198, 184, 182, 170, 134, 120.
Anal. Calcd for C16H22BrNO: C, 59.27; H, 6.84; N, 4.32. Found: C,
59.05; H, 6.98; N, 4.48.
MS (EI): m/z = 215 (M+, 100%), 200, 172, 144, 130, 90.
2-(2-Bromopyridin-3-ylmethyl)-1-(but-3-enyl)cycloheptanol
(34)
Prepared from 18 following the typical procedure for 33; white sol-
Anal. Calcd for C15H21N: C, 83.67; H, 9.83; N, 6.5. Found: C,
83.54; H, 9.77; N, 6.65.
id; yield: 61%; mp 72–73 °C.
IR (KBr): 3379, 2927, 1641, 1561, 1445, 1401, 900 cm–1.
5a-Methyl-5,5a,6,7,8,9,10,11-octahydrobenzo[4,5]cyclohep-
ta[1,2-b]pyridin-9a-ol (37) and 5a,10-Dimethyl-5,6,7,8,9,10-
hexahydro-5aH-benzo[g]quinolin-9a-ol (38)
37
White solid; yield: 74%; mp 84–85 °C.
IR (KBr): 3423, 2925, 1679, 1586, 1450, 1076, 782 cm–1.
1H NMR: d = 1.15–2.01 (14 H, m), 2.21 (2 H, q-like, J = 7.3 Hz),
2.58 (1 H, dd, J = 11.6, 13.8 Hz), 3.05 (1 H, d, J = 13.8 Hz), 4.99 (1
H, d, J = 10.0 Hz), 5.08 (1 H, d, J = 17.2 Hz), 5.81–5.95 (1 H, m),
7.20 (1 H, dd, J = 5.0, 7.1 Hz), 7.49 (1 H, d, J = 7.5 Hz), 8.23 (1 H,
d, J = 4.4 Hz).
13C NMR: d = 21.9 (CH2), 25.9 (CH2), 27.8 (CH2), 28.1 (CH2), 29.2
(CH2), 35.8 (CH2), 38.7 (CH2), 39.2 (CH2), 47.3 (CH), 76.7 (C),
114.6 (CH2), 122.5 (CH), 138.6 (C), 139.0 (CH), 139.8 (CH), 144.9
(C), 147.6 (CH).
The NMR spectra contained broad signals in the aliphatic region at-
tributed to conformational equilibrium. Only the following signals
could be distinguished.
1H NMR: d = 0.86 (3 H, s), 0.89–1.90 (11 H, m), 2.11–3.64 (4 H,
m), 7.03 (1 H, t-like, J = 5.8 Hz), 7.32 (1 H, d, J = 6.9 Hz), 8.30 (1
H, d, J = 4.0 Hz).
MS (EI): m/z = 339 (M+ for 81Br), 337 (M+ for 79Br), 284, 282, 258
(100%), 200, 198, 186, 184, 120.
13C NMR: d = 146.9 (CH), 138.0 (CH), 121.6 (CH), 75.7 (C).
MS (EI): m/z = 231 (M+), 202, 188, 179, 175, 160, 144, 138 (100%),
132, 118.
Anal. Calcd for C17H24BrNO: C, 60.36; H, 7.15; N, 4.14. Found: C,
60.12; H, 7.25; N, 4.29.
Anal. Calcd for C15H21NO: C, 77.88; H, 9.15; N, 6.05. Found: C,
78.11; H, 9.32; N, 5.87.
Radical Cyclization of 19–34; General Procedure
To a gently stirred refluxing solution (0.002–0.003 M) of the re-
spective olefin 19–34 in degassed anhyd benzene was added a solu-
tion of Bu3SnH (1.2 equiv) and AIBN (15 mol%) in the same
solvent over a period of ca 3.5 h. After addition, the mixture was
further refluxed for 4 h and the benzene was removed. The residue
was taken in Et2O (50 mL) and stirred vigorously with sat. aq KF
(50 mL) at r.t. for 10 h. The organic phase was separated and the
aqueous phase was extracted with Et2O. The combined organic
phases were washed with brine, dried and concentrated to give the
crude product which was chromatographed (EtOAc–petroleum
ether).
38
White solid; yield: 16%; mp 75–76 °C.
IR (KBr): 3288, 2931, 2858, 1582, 1448, 1030, 791 cm–1.
1H NMR: d = 0.85–0.95 (2 H, m), 1.16 (3 H, s), 1.30–1.81 (7 H, m,
overlapped with 3 H, d, J = 7.1 Hz at 1.49), 2.39 (1 H, d, J = 16.8
Hz), 3.02 (1 H, d, J = 16.9 Hz), 3.27 (1 H, q, J = 6.6 Hz), 7.04 (1 H,
dd, J = 4.8, 7.1 Hz), 7.34 (1 H, d, J = 7.3 Hz), 8.44 (1 H, d, J = 3.7
Hz).
13C NMR: d = 13.3 (CH3), 20.5 (CH2), 21.9 (CH3), 23.0 (CH2), 32.4
(CH2), 34.1 (CH2), 37.3 (C), 39.9 (CH2), 39.9 (CH), 74.4 (C), 121.0
(CH), 129.7 (C), 136.5 (CH), 147.1 (CH), 158.3 (C).
5a-Methyl-5,5a,6,7,8,9,9a,10-octahydrobenzo[g]quinoline (35)
Waxy solid; yield: 90%.
IR (KBr): 2922, 2855, 1642, 1574, 1444, 869, 794 cm–1.
MS (EI): m/z = 231 (M+), 203, 174, 160, 120 (100%).
Anal. Calcd for C15H21NO: C, 77.88; H, 9.15; N, 6.05. Found: C,
77.71; H, 9.25; N, 5.81.
Synthesis 2005, No. 18, 3067–3078 © Thieme Stuttgart · New York

3076
S. Maiti et al.
PAPER
6,6-Dimethyl-5,5a,6,7,8,9,10,11-octahydrobenzo[4,5]cyclohep-
ta[1,2-b]pyridin-9a-ol (39) and 6,6,10-Trimethyl-5,6,7,8,9,10-
hexahydro-5aH-benzo[g]quinolin-9a-ol (40)
39
Anal. Calcd for C15H21NO: C, 78.32; H, 9.45; N, 5.71. Found: C,
78.07; H, 9.58; N, 5.84.
1-(But-2-enyl)-3,3-dimethyl-2-(pyridin-3-ylmethyl)cyclohex-
anol (43)
White solid; yield: 75%; mp 202–203 °C.
Colorless oil: yield: 51%.
IR (neat): 3365 cm–1.
1H NMR: d = 0.98 (3 H, s), 1.09 (3 H, s), 1.20–1.53 (7 H, m), 1.60
(3 H, d, J = 4.7 Hz), 1.63–1.86 (2 H, m), 2.04–2.11 (1 H, m), 2.71–
2.80 (1 H, m), 2.93 (1 H, dd, J = 6.3, 16.0 Hz), 5.18–5.25 (2 H, m),
7.20 (1 H, dd, J = 4.8, 7.6 Hz), 7.56 (1 H, d, J = 7.8 Hz), 8.41 (1 H,
br s), 8.54 (1 H, d, J = 6.8 Hz).
IR (KBr): 3242, 2997, 2955, 2858, 1583, 1445, 915, 770 cm–1.
1H NMR: d = 1.00 (3 H, s), 1.05 (3 H, s), 1.11–1.26 (3 H, m), 1.33–
1.62 (4 H, m), 1.72–1.89 (2 H, m), 2.04 (1 H, br s), 2.43 (1 H, d,
J = 4.3 Hz), 2.79 (1 H, dd, J = 6.8, 14.3 Hz), 3.17 (1 H, dd,
J = 10.4, 14.2 Hz), 3.53 (1 H, t, J = 13.5 Hz), 7.05 (1 H, dd, J = 5.1,
7.3 Hz), 7.40 (1 H, d, J = 7.4 Hz), 8.27 (1 H, d, J = 4.6 Hz).
13C NMR: d = 18.0 (CH2), 21.3 (CH3), 29.7 (CH2), 31.8 (CH3), 32.1
(CH2), 34.3 (C), 41.8 (CH2), 42.37 (CH2), 42.41 (CH2), 53.1 (CH),
73.3 (C), 121.4 (CH), 135.6 (CH), 138.4 (C), 145.8 (CH), 162.9 (C).
MS (EI): m/z (%) = 274 (M+ + 1), 273 (M+), 258, 219 (100%), 218
(100%), 150, 107, 96, 69.
MS (EI): m/z = 245 (M+), 230, 227, 212, 188, 174, 157, 132 (100%),
91.
Anal. Calcd for C18H27NO: C, 79.07; H, 9.95; N, 5.12. Found: C,
78.87; H, 10.14; N, 4.98.
Anal. Calcd for C16H23NO: C, 78.32; H, 9.45; N, 5.71. Found: C,
78.07; H, 9.61; N, 5.57
cis- and trans-5a,6,7,8,8a,9-Hexahydro-5H-cyclopenta[g]quino-
line (44)
Colorless oil; yield: 90%.
IR (neat): 2862, 1577, 1438, 1114, 897 cm–1.
40
White solid; yield: 20%; mp 125–126 °C.
IR (KBr): 3348, 2938, 2869, 1579, 1443, 1383, 1161, 941 cm–1.
1H NMR: d = 1.15–3.26 (12 H, m, alicyclic CH2 and CH), 7.05 (1
H, dd, J = 5.1, 7.3 Hz), 7.36 (1 H, br d, J = 6.6 Hz), 8.33 (1 H, br d,
J = 4.7 Hz).
13C NMR: d = 23.3 (CH2), 25.9 (CH2), 31.7 (CH2), 32.0 (CH2), 33.9
(CH2), 34.1 (CH2), 34.3 (CH2), 35.5 (CH2), 37.3 (CH2), 38.0
(2 × CH), 39.7 (CH2), 42.8 (CH), 43.4 (CH), 121.2 (CH), 121.7
(CH), 132.9 (C), 134.2 (C), 135.4 (CH), 137.6 (CH), 146.8 (CH),
147.0 (CH), 158.3 (C), 160.3 (C).
1H NMR: d = 0.98 (3 H, s), 1.10 (3 H, s), 1.25–1.40 (3 H, m), 1.44
(3 H, d, J = 7.1 Hz), 1.50–1.56 (2 H, m), 1.73–1.88 (2 H, m), 2.10
(1 H, br d, J = 12.9 Hz), 2.69–2.82 (2 H, m), 2.96 (1 H, dd, J = 13.3,
16.0 Hz), 7.05 (1 H, dd, J = 4.8, 7.4 Hz), 7.39 (1 H, d, J = 7.5 Hz),
8.42 (1 H, d, J = 4.4 Hz).
13C NMR: d = 11.0 (CH3), 17.8 (CH2), 21.7 (CH3), 25.7 (CH2), 31.6
(CH3), 33.6 (C), 37.8 (CH2), 41.7 (CH2), 47.8 (CH), 48.2 (CH), 72.1
(C), 120.8 (CH), 131.4 (C), 135.8 (CH), 146.6 (CH), 157.6 (C).
MS (EI): m/z = 173 (M+, 100%), 144, 130.
MS (EI): m/z = 245 (M+), 230 (100%), 217, 188, 174, 160, 132.
Anal. Calcd for C12H15N: C, 83.19; H, 8.73; N, 8.08. Found: C,
83.04; H, 8.83; N, 8.16.
Anal. Calcd for C16H23NO: C, 78.32; H, 9.45; N, 5.71. Found: C,
78.49; H, 9.57; N, 5.53.
cis- and trans- 5a,6,7,8,9,10,10a,11-Octahydro-5H-cyclohep-
ta[g]quinoline (45)
Colorless oil, yield: 90%.
IR (neat): 3049, 2919, 2854, 1576, 1446, 1111, 785 cm–1.
11,11-Dimethyl-6,7,8,9,10,11,11a,12-octahydro-5H-4-azadiben-
zo[a,d]cycloocten-7a-ol (41)
White solid; yield: 65%; mp 122–123 °C.
IR (KBr): 3245, 2935, 2867, 1581, 1648, 1210, 777 cm–1.
1H NMR: d = 1.31–2.98 (16 H, m, alicylic CH2 and CH), 7.02 (1 H,
dd, J = 4.5, 7.5 Hz), 7.34 (1 H, d, J = 7.5 Hz), 8.33 (1 H, d, J = 3.8
Hz).
13C NMR: d = 25.8 (2 CH2), 26.2 (CH2), 26.3 (CH2), 28.7 (CH2),
29.1 (CH2), 32.1 (CH2), 32.4 (CH2), 33.4 (CH2), 33.5 (CH2), 35.3
(CH2), 36.6 (CH), 36.8 (CH), 38.1 (CH2), 38.4 (CH2), 41.6 (CH2),
41.7 (CH), 41.9 (CH), 120.9 (CH), 121.0 (CH), 136.3 (CH), 136.6
(CH), 136.6 (C), 144.3 (CH), 146.2 (CH), 157.6 (C).
1H NMR: d = 1.05 (3 H, s), 1.12 (3 H, s), 1.17–1.53 (7 H, m), 1.60–
1.85 (4 H, m), 1.99–2.08 (1 H, m), 2.62 (1 H, d, J = 14.0 Hz), 2.83–
3.00 (2 H, m), 3.27–3.37 (1 H, m), 7.09 (1 H, dd, J = 5.0, 7.4 Hz),
7.43 (1 H, d, J = 7.6 Hz), 8.37 (1 H, d, J = 4.7 Hz).
13C NMR: d = 18.4 (CH2), 21.6 (CH3), 25.1 (CH2), 29.3 (CH2), 32.8
(CH3), 33.5 (CH2), 35.0 (C), 39.0 (CH2), 41.9 (CH2), 45.0 (CH2),
59.6 (CH), 74.2 (C), 121.5 (CH), 136.5 (CH), 138.6 (C), 146.8
(CH), 159.8 (C).
MS (EI): m/z = 201 (M+, 100%), 186, 172, 158, 144, 130.
MS (EI): m/z = 259 (M+), 244, 231, 216, 202, 188, 146, 132, 119,
107, 69, 55 (100%).
Anal. Calcd for C14H19N: C, 83.53; H, 9.51; N, 6.96. Found: C,
83.70; H, 9.40; N, 6.87.
Anal. Calcd for C17H25NO: C, 78.72; H, 9.71; N, 5.40. Found: C,
78.85; H, 9.81; N, 5.32.
9-Methyl-5,5a,6,7,8,9-hexahydrocyclopenta[g]quinolin-8a-ol
(46)
White solid; yield: 65%; mp 124–125 °C.
IR (KBr): 3348, 2932, 2864, 1586, 1438, 1381, 783 cm–1.
2-Methyl-1-(prop-1-enyl)-2-(pyridin-3-ylmethyl)cyclohexanol
(42)
White solid; yield: 39 mg (51%); mp 105–107 °C.
IR (KBr): 3415, 1545 cm–1.
1H NMR: d = 0.83 (3 H, s), 1.02–1.06 (1 H, m), 1.26–1.91 (8 H, m,
overlapped with 3 H, d, J = 4.4 Hz at 1.77), 2.59 (1 H, d, J = 13.1
Hz), 2.87 (1 H, d, J = 13.2 Hz), 5.73 (2 H, s) 7.17 (1 H, dd, J = 4.8,
7.6 Hz), 7.44 (1 H, d, J = 7.7 Hz), 8.37–8.42 (2 H, m).
1H NMR: d = 1.21 (1 H, s), 1.53 (3 H, d, J = 7.0 Hz), 1.63–1.79 (3
H, m), 1.85–1.97 (4 H, m), 2.83–2.95 (3 H, m), 7.05 (1 H, dd,
J = 4.8, 7.6 Hz), 7.34 (1 H, d, J = 7.6 Hz), 8.40 (1 H, d, J = 4.4 Hz).
13C NMR: d = 12.7 (CH3), 21.2 (CH2), 28.8 (CH2), 30.4 (CH2), 38.0
(CH2), 44.0 (CH), 46.3 (CH), 81.1 (C), 120.9 (CH), 131.4 (C), 136.7
(CH), 147.1 (CH), 159.1 (C).
MS (EI): m/z = 245 (M+), 230, 176, 161, 148, 134 (100%).
MS (EI): m/z = 203 (M+), 186 (100%), 160, 146, 132, 118.
Synthesis 2005, No. 18, 3067–3078 © Thieme Stuttgart · New York

PAPER
Synthesis of Pyridine-Fused Linear Tricyclic Systems
3077
Anal. Calcd for C13H17NO: C, 76.81; H, 8.43; N, 6.89. Found: C,
76.63; H, 8.55; N, 6.77.
(1 H, dt, J = 4.1, 12.7 Hz), 7.06 (1 H, dd, J = 4.7, 7.6 Hz), 7.39 (1
H, d, J = 7.6 Hz), 8.40 (1 H, dd, J = 1.4, 4.7 Hz).
13C NMR: d = 18.7 (CH2), 21.4 (CH2), 26.4 (CH2), 28.0 (CH2), 30.8
(CH2), 31.5 (CH2), 33.5 (CH2), 37.4 (CH2), 37.8 (CH2), 46.6 (CH),
75.2 (C), 121.6 (CH), 136.4 (CH), 138.6 (C), 147.2 (CH), 158.6 (C).
MS (EI): m/z = 245 (M+), 227, 216, 188, 174, 160, 146, 134 (100%),
132, 118, 107.
1,2,3,4,5,6,11,11a-Octahydro-7-azabenzo[a] cyclopenta[d]cy-
cloocten-3a-ol (47)
White solid; yield: 70%; mp 93–94 °C.
IR (KBr): 3364, 2937, 2858, 1582, 1453, 900, 841 cm–1.
1H NMR: d = 1.06 (1 H, dt, J = 4.9, 14.0 Hz), 1.51–1.93 (10 H, m),
2.05–2.12 (1 H, m), 2.48 (1 H, dd, J = 13.2, 1.6 Hz), 2.79–2.86 (1
H, m), 2.99 (1 H, dd, J = 11.5, 13.7 Hz), 3.38 (1 H, dt, J = 5.7, 12.6
Hz), 7.04 (1 H, dd, J = 4.9, 7.5 Hz), 7.39 (1 H, dd, J = 1.2, 7.6 Hz),
8.40 (1 H, dd, J = 1.4, 4.8 Hz).
13C NMR: d = 19.2 (CH2), 25.9 (CH2), 31.8 (CH2), 32.6 (CH2), 33.4
(CH2), 33.9 (CH2), 44.3 (CH2), 54.6 (CH), 80.6 (C), 121.3 (CH),
136.7 (CH), 137.0 (C), 147.4 (CH), 160.2 (C).
Anal. Calcd for C16H23NO: C, 78.32; H, 9.45; N, 5.71. Found: C,
78.52; H, 9.36; N, 5.56.
trans-7-Azatricyclo[11.5.0.03,8]octadeca-3,5,7-trien-13-ol (51)
and cis-7-Azatricyclo[11.5.0.03,8]octadeca-3,5,7-trien-13-ol (52)
51
White solid; yield: 23 mg (30%); mp 126–127 °C.
IR (KBr): 3234, 2928, 1577, 1450, 1336, 1172, 923, 770 cm–1.
1H NMR: d = 0.86–0.93 (2 H, m), 1.25–1.89 (14 H, m), 1.99–2.07
(2 H, m), 2.19 (1 H, dd, J = 3.2, 14.8 Hz), 2.82 (1 H, m), 3.18 (1 H,
dd, J = 3.9, 14.7 Hz), 3.29 (1 H, dt, J = 4.5, 12.4 Hz), 7.07 (1 H, dd,
J = 4.9, 7.6 Hz), 7.45 (1 H, d, J = 7.5 Hz), 8.41 (1 H, dd, J = 1.3,
4.6 Hz).
13C NMR: d = 19.2 (CH2), 21.8 (CH2), 26.2 (CH2), 27.0 (CH2), 27.4
(CH2), 31.9 (CH2), 33.3 (CH2), 35.8 (CH2), 40.2 (CH2), 41.5 (CH2),
49.3 (CH), 77.7 (C), 121.6 (CH), 136.3 (CH), 138.9 (C), 147.2
(CH), 158.6 (C).
MS (EI): m/z = 217 (M+), 199, 189, 171, 146, 134, 132, 120, 118,
107 (100%).
Anal. Calcd for C14H19NO: C, 77.38; H, 8.81; N, 6.45. Found: C,
77.60; H, 8.93; N, 6.31.
7-Azatricyclo[10.5.0.03,8]heptadeca-3,5,7-trien-12-ol (48)
Colorless oil; yield: 65%.
IR (neat): 3348, 3063, 2924, 1580, 1450, 1271, 1054, 801 cm–1.
1H NMR: d = 0.98 (1 H, s), 1.35–1.41 (2 H, m), 1.43–1.89 (12 H,
m), 2.00–2.07 (1 H, m), 2.59 (1 H, dd, J = 2.7, 14.1 Hz), 2.92 (1 H,
dt, J = 5.7, 12.9 Hz), 3.07 (1 H, dd, J = 9.2, 14.1 Hz), 3.16–3.26 (1
H, m), 7.06 (1 H, dd, J = 4.8, 7.5 Hz), 7.46 (1 H, d, J = 7.6 Hz), 8.38
(1 H, dd, J = 1.6, 4.8 Hz).
13C NMR: d = 20.9 (CH2), 25.0 (CH2), 26.8 (CH2), 27.2 (CH2), 30.9
(CH2), 35.2 (CH2), 38.7 (CH2), 40.0 (CH2), 47.7 (CH2), 52.9 (CH),
75.4 (C), 121.3 (CH), 136.8 (C), 137.3 (CH), 146.9 (CH), 160.1 (C).
MS (EI): m/z = 259 (M+), 244, 230, 216, 202, 188, 174, 160, 148,
146, 144, 134, 132, 120, 118, 107 (100%).
Anal. Calcd for C17H25NO: C, 78.72; H, 9.71; N, 5.40. Found: C,
78.96; H, 9.60; N, 5.31.
52
White solid; yield: 13 mg (17%); mp 159–160 °C.
MS (EI): m/z = 245 (M+), 217, 204, 199, 188, 174, 160, 146, 132,
IR (KBr): 3284, 2919, 1576, 1453, 1244, 1173, 809, 773 cm–1.
120, 118, 107 (100%).
1H NMR: d = 0.89–1.95 (18 H, m), 2.51 (1 H, dd, J = 3.3, 14.6 Hz),
2.62 (1 H, dd, J = 4.1, 14.4 Hz), 2.82 (1 H, m), 3.20 (1 H, dt, J = 4.3,
12.7 Hz), 7.06 (1 H, dd, J = 4.8, 7.6 Hz), 7.41 (1 H, d, J = 7.4 Hz),
8.41 (1 H, d, J = 3.4 Hz).
Anal. Calcd for C16H23NO: C, 78.32; H, 9.56; N, 5.71. Found: C,
78.45; H, 9.40; N, 5.58.
2,3,4,5,6,7,12,12a-Octahydro-1H-8-azabenzo[a]cyclopen-
ta[d]cyclononen-3a-ol (49)
The fractions eluted with 20–25% EtOAc in petroleum ether fur-
nished 49 as a white solid; yield: 35%; mp 143–144 °C.
IR (KBr): 3303, 2942, 1576, 1449, 1145, 912, 800 cm–1.
1H NMR: d = 0.79–0.92 (2 H, m), 1.13–1.26 (1 H, m), 1.45–1.82 (7
H, m), 1.84–2.00 (1 H, m), 2.02–2.11 (2 H, m), 2.25–2.35 (1 H, m),
2.78 (1 H, dd, J = 9.6, 14.8 Hz), 2.93–3.04 (2 H, m), 3.14–3.20 (1
H, m), 7.09 (1 H, dd, J = 4.9, 7.5 Hz), 7.46 (1 H, d, J = 7.4 Hz), 8.05
(1 H, d, J = 4.7 Hz).
13C NMR: d = 21.0 (CH2), 22.3 (CH2), 29.6 (CH2), 33.5 (CH2), 34.2
(CH2), 35.1 (CH2), 37.0 (CH2), 41.9 (CH2), 43.9 (CH), 82.9 (C),
121.3 (CH), 135.3 (C), 138.8 (CH), 146.9 (CH), 161.6 (C).
13C NMR: d = 17.7 (CH2), 19.8 (CH2), 21.7 (CH2), 27.1 (CH2), 27.5
(CH2), 27.9 (CH2), 31.5 (CH2), 31.7 (CH2), 38.8 (CH2), 39.6 (CH2),
48.5 (CH), 78.0 (C), 121.5 (CH), 136.5 (CH), 138.6 (C), 147.3
(CH), 158.5 (C).
MS (EI): m/z = 259 (M+), 244, 230, 216, 202, 188, 174, 160, 148,
146, 134, 132, 120, 118, 107 (100%).
Anal. Calcd for C17H25NO: C, 78.72; H, 9.71; N, 5.40. Found: C,
78.46; H, 9.87; N, 5.57.
Crystallographic Data for 37, 39, and 50
37
C15H23NO2 M = 249.34, monoclinic, P21/a, Z = 4, a = 8.551(12),
b = 12.028(14), c = 13.746(14) Å, β = 95.95(1)°, U = 1406.2 Å3,
d
calcd = 1.178 g cm–3.
MS (EI): m/z = 231 (M+), 202, 189, 174, 160, 146, 134, 132, 118,
107 (100%).
39
Anal. Calcd for C15H21NO: C, 77.88; H, 9.15; N, 6.05. Found: C,
78.10; H, 9.01; N, 5.91.
C16H23NO, M = 245.35, triclinic, P-1, Z = 4, a = 10.836(12),
b = 10.970(12), c = 13.136(14) Å, a = 88.63(1), b = 68.32(1),
g = 74.79(1)°, U = 1395.6 Å3, dcalcd = 1.170 g cm–3.
5,6,7,8,9,10,11,12,12a,13-Decahydro-4-azadibenzo[a,d]cy-
clononen-8a-ol (50)
White solid; yield: 35 mg (61%); mp 109–110 °C.
IR (KBr): 3265, 2935, 2855, 1577, 1449, 1097, 775 cm–1.
1H NMR: d = 0.86–0.93 (1 H, m), 1.11–1.89 (14 H, m), 1.99–2.09
(2 H, m), 2.76–2.83 (1 H, m), 3.12 (1 H, dd, J = 3.5, 14.5 Hz), 3.33
50
C16H23NO, M = 245.35, monoclinic, P21/c, Z = 4, a = 9.326(11),
b = 10.632(12), c = 14.156(15) Å, b = 92.98(1)°, U = 1401.7 Å3,
d
calcd = 1.163 g cm–3.
Data for all three crystals were measured with MoKa radiation us-
ing the MAR research Image Plate System. The crystals were posi-
Synthesis 2005, No. 18, 3067–3078 © Thieme Stuttgart · New York

3078
S. Maiti et al.
PAPER
tioned at 70 mm from the Image Plate. 100 frames were measured
at 2° intervals with a counting time of 2 min. Data Anal was carried
out with the XDS program18 to provide 2659, 2076, 4989 indepen-
dent reflections, respectively. The structures were solved using di-
rect methods with the ShelX86 program.19 Non-hydrogen atoms
were refined with anisotropic thermal parameters. The hydrogen at-
oms were included in geometric positions and given thermal para-
meters equivalent to 1.2 times those of the atom to which they were
attached. The structures were refined on F2 using ShelXL20 to R1
0.1121, 0.0934, 0.0679; wR2 0.2101, 0.1810, 0.1485 for 1610,
1890, 2227 reflections respectively all with I > 2s(I). The data have
been deposited at the Cambridge Crystallographic Data Centre
(CCDC 252212 through CCDC 252214 inclusive).
(3) (a) Mohanakrishnan, A. K.; Srinivasan, P. C. Tetrahedron
Lett. 1996, 37, 2659. (b) Flanagan, S. R.; Harrowven, D. C.;
Bradley, M. Tetrahedron Lett. 2003, 44, 1795. (c) Dobbs,
A. P.; Jones, K.; Veal, K. T. Tetrahedron Lett. 1997, 38,
5379. (d) Yokoyama, Y.; Matsushima, H.; Takashima, M.;
Suzuki, T.; Murakami, Y. Heterocycles 1997, 46, 133.
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1994, 35, 5331. (f) Kato, I.; Higashimoto, M.; Tamura, O.;
Ishibashi, H. J. Org. Chem. 2003, 68, 7983.
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Lett. 1985, 26, 6001. (b) Dobbes, A. P.; Jones, K.; Veal, K.
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2000, 56, 397.
(5) Maiti, S.; Achari, B.; Mukherjee, R.; Banerjee, A. K. J.
Chem. Soc., Perkin Trans. 1 2002, 1769.
Acknowledgment
(6) Banerjee, M.; Mukherjee, R.; Achari, B.; Banerjee, A. K.
Org. Lett. 2003, 5, 3931.
We are grateful to Prof. U. R. Ghatak of our institute for his valuable
suggestions and criticism, and CSIR for the award of a Research
Fellowship to S.M. We also thank EPSRC (U.K.) and the Universi-
ty of Reading for funds for the Image Plate system.
(7) (a) Banik, B. K.; Chakraborty, A. K.; Ghatak, U. R. J. Chem.
Res., Synop. 1986, 406. (b) Banik, B. K.; Chakraborty, A.
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1974, 30, 187.
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Synthesis 2005, No. 18, 3067–3078 © Thieme Stuttgart · New York