Pyrylium Salts via Electrophilic Cyclization: Applications for Novel 3-Arylisoquinoline Syntheses

Full text of DOI:10.1021/jo990810x

J . Org. Chem. 1999, 64, 6499-6504
6499
tocol provided a variety of ortho-ynone cyclization precur-
sors as presented in Table 1.6
P yr yliu m Sa lts via Electr op h ilic
Cycliza tion : Ap p lica tion s for Novel
3-Ar ylisoqu in olin e Syn th eses
With these precursors, we proceeded to investigate the
scope of the proposed cyclization. While trifluoroacetic
acid induced a partial degree of apparent cyclization, we
found that the reaction proceeded slowly and that the
resulting products eluded isolation. As listed in Table 2,
use of stronger acids such as HBF4 and TfOH provided
an instant and essentially quantitative cyclization. Com-
pounds 3c-e (R1 ) NMe2) and compounds 3m ,n (R1 )
Ph) initially precipitated out of solution with diethyl ether
in 60-80% yields. A second precipitation from MeCN/
CH2Cl2 provided analytically pure samples. Common to
all systems, we found that the reaction required high
dilution (0.005 M) and exclusion of water in order to
suppress intermolecular chemistry and hydrolysis, re-
spectively. Significantly higher concentrations led to the
formation of intractable materials.
J ohn D. Tovar and Timothy M. Swager*
Department of Chemistry, Massachusetts Institute of
Technology, 77 Massachusetts Avenue,
Cambridge, Massachusetts 02139
Received May 17, 1999
Pyrylium salts have found uses in many areas of
pharmaceutical and materials chemistry as versatile
synthetic intermediates for complex heterocyclic skel-
etons and for their intriguing physical properties.1 Earlier
work in our laboratories explored acid-catalyzed electro-
philic cyclizations of aryl acetylenes to provide fully
aromatized conjugated materials.2 Our continued interest
in highly unsaturated ladder polymers and related
materials has led us to extend this methodology to a new
one-component synthesis of pyrylium salts through the
use of a carbonyl group in lieu of a proximal arene moiety.
According to our proposed mechanism, electrophilic at-
tack at the â carbon of 2 results in a carbocation
formation at the R carbon, thereby leading to ring closure
of intermediate A via lone pair attack (Scheme 1). In this
report, we present the scope of a novel acid-induced
cyclization of ortho-alkynylated aromatic carbonyl func-
tionalities into the isobenzopyrylium salts depicted by 3.
In addition, we describe efficient one- and/or two-pot
preparations of the corresponding 3-arylisoquinolines
which can serve as key intermediates in the synthesis of
many isoquinoline alkaloids but have proven difficult to
access through current methodology.3
Stetter and Reischl demonstrated that (Z)-1,5-diphe-
nyl-2-penten-4-ynone underwent cyclization to the pyry-
lium perchlorate upon exposure to perchloric acid.4
However, the inherent difficulty of Z-selective substrate
preparation diminished the practicality of this finding.1a
More recently, Neuenschwander and co-workers found
that a variety of 5-amino-2-penten-4-ynones cyclized to
pyrylium salts in one or two steps upon exposure to HF,
HCl, HBr, or HI.5 In light of this, we endeavored to
extend these precedents to aryl systems. Utilization of a
synthetically facile modified Sonogashira-Hagihara pro-
In contrast to our earlier findings,2 the cyclization does
not require a strong para-electron-donating group on the
aryl acetylene to stabilize the positive charge density of
the R carbon of A as evidenced by the phenyl and tolyl
entries for R2 in Table 2. In fact, in situ NMR observa-
tions of acetylenes 2e and 2m (with decyloxy donors)
showed two distinct products upon intermediate exposure
to TfOH and TfOD. Reaction times over 1 day provided
one cyclized yet undesired product, apparently the result
of decyloxy ether cleavage.7 NMR showed the presence
of only 1 product after 15 min, and keeping reaction times
around 30 min provided one isolated product (e.g. in the
case of 3e). Our findings show that the cyclization
requires substrates with phenyl-substituted alkynes in
order to obtain the desired reactivity: the use of alkyl
acetylenes (R2 ) n-Bu) led to at least two different and
unisolable products while silyl and free acetylenes (R2 )
TMS, H) led to the formation of undesired and apparently
noncyclized olefinic products, all as observed by 1H NMR.8
Distinct spectroscopic changes accompanied all pyry-
lium formations. Immediately upon acid addition, an
intense red to yellow UV fluorescence developed which
persisted in the precipitate. Upon cyclization, the exo-
cyclic amine compounds 3c-e (R1 ) NMe2) displayed a
new UV-vis absorbance between 370 and 400 nm while
the 1-phenyl compounds 3m -o (R1 ) Ph) absorbed in
the 440-450 nm range. Representative fluorescence data
for the isolated salts displayed Stokes shifts of greater
than 100 nm, suggesting excited state planarization of
the pendant aryl moiety. All isolated salts lacked the
(1) For some leading reviews, see: (a) Dimroth, K.; Wolf, K. H. In
Newer Methods of Preparative Organic Chemistry; Foerst, W., Ed.
Academic Press: New York, 1964; Vol. 3, pp 357-423. (b) Balaban, A.
T.; Schroth, W.; Fischer, G. In Advances in Heterocyclic Chemistry;
Katritzky, A. R., Boulton, A. J ., Eds.; Academic Press: New York, 1969;
Vol. 10, pp 241-326. (c) Balaban, A. T.; Dinculescu, A.; Dorofeenko,
G. N.; Fischer, G. W.; Koblik, A. V.; Mezheritskii, V. V.; Schroth, W.
Pyrylium Salts: Syntheses, Reactions, and Physical Properties; Aca-
demic Press: New York, 1982.
alkynyl C-C stretch in the infrared spectra (2200 cm-1
)
while they exhibited an intense stretching band charac-
teristic of their respective counteranion (1260 cm-1 for
TfO-, 1060 cm-1 for BF4-). High-resolution MS provided
evidence for both the intact cation (EI or FAB) as well
as the counteranion (negative ion FAB), and all isolated
salts gave satisfactory elemental analyses. In the 13C
(2) (a) Goldfinger, M. B.; Swager, T. M. J . Am. Chem. Soc. 1994,
116, 7895-7896. (b) Goldfinger, M. B.; Crawford, K. B.; Swager, T. M.
J . Am. Chem. Soc. 1997, 119, 4578-4593. (c) Goldfinger, M. B.;
Crawford, K. B.; Swager, T. M. J . Org. Chem. 1998, 63, 1668-1675.
(3) For representative synthetic strategies, see: (a) Bradsher, C. K.;
Wallis, T. G. Tetrahedron Lett. 1972, 3149-3150. (b) Garcia, A.; Lete,
E.; Villa, M. J .; Dominguez, E.; Badia, M. D. Tetrahedron 1988, 44,
6681-6686. (c) Fitzgerald, J . J .; Michael, F. E.; Olofson, R. A.
Tetrahedron Lett. 1994, 35, 9191-9194.
(6) Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetrahedron Lett. 1975,
4467-4470.
(7) Disappearance of the decyloxy group’s R-proton triplet (4.18 ppm)
led us to this conclusion.
(8) A distinct 1H NMR resonance initially appeared at 5.70 ppm (dd,
2H, J ) 13.5, 5.0 Hz) and with further exposure to TfOH shifted to
5.83 ppm (dd, J ) 19.5, 4.5 Hz) for both 3a and 3b, indicative of olefinic
protons and residual F--promoted TMS cleavage.
(4) Stetter, H.; Reischl, A. Chem. Ber. 1960, 93, 1253-1256.
(5) Fischer, F.; Berger, D.; Neuenschwander, M. Helv. Chim. Acta
1998, 81, 1792-1802.
10.1021/jo990810x CCC: $18.00 © 1999 American Chemical Society
Published on Web 08/20/1999

6500 J . Org. Chem., Vol. 64, No. 17, 1999
Notes
Sch em e 1
Ta ble 1. Cycliza tion P r ecu r sor s 2 via
Son oga sh ir a -Ha gih a r a Cou p lin g of o-Iod oben zen es 1
a n d Ter m in a l Acetylen es
ambient conditions. In concurrence with the results for
other R-amino pyrylium salts,9 NMR data indicated that
these aminated compounds displayed a significant degree
of exocyclic charge localization onto the nitrogen sub-
stituent. The N-methyl protons appeared as two singlets
a
entry
R1
R2
yield/%
a
b
c
d
e
f
g
h
i
j
k
l
m
n
o
p
NMe2
TMS
H
Ph
81
85b
87c
67c
66
1
in the H spectrum between 3.7 and 3.9 ppm, and two
distinct N-methyl carbon resonances appeared around
43-46 ppm in the 13C spectrum. The persistence of imine
character in these salts displayed itself in the small
upfield shift of the carbonyl carbon observed in the 13C
spectrum upon cyclization (C1 of 3). When compared to
the other pyrylium salts discussed below, the new proton
singlet observed at 7.5-7.6 ppm upon cyclization (Ha of
3) indicated decreased aromatic character, lending cre-
dence to the argument that exocyclic charge localization
reduces aromaticity. To further verify this claim, the
crystal structure determined for 3d supports a structure
with significant exocyclic double bond character as
evidenced by the short C1-N bond of 1.314 Å (typical
arylamine value 1.39 Å).10
With the absence of a strong nitrogen donor in the ester
or aldehyde carbonyl functions, aromaticity should domi-
nate for the ethoxy and protio pyrylium systems (R1 )
OEt, H). Indeed, these two systems displayed lower field
1H singlet resonances for Ha at 8.1 and 8.6 ppm, respec-
tively. Unfortunately, the isolation of these salts proved
problematic. The tetrafluoroborate salts 3f,g (R1 ) OEt)
precipitated out of solution but slowly hydrolyzed at
ambient conditions to provide the corresponding isocou-
marin compounds 5a ,b within hours. This instability
p-tol
p-OC10
TMS
Ph
p-tol
p-OC10
TMS
Ph
p-tol
p-OC10
Ph
p-tol
n-Bu
OEt
H
89
84
90
55
84d
36d
79d
72d
65
Ph
54
87
a
b
p-tol ) 4-Me-C6H4-, p-OC10 ) 4-(n-C10H21)-C6H4-. Pre-
pared by deprotection of 2a (K2CO3/MeOH/THF). c Difficulty in
removing 1 required a yield determination by 1H NMR integration.
d
Overall yield from o-iodobenzyl alcohol coupling (in place of 1)
followed by PCC oxidation.
Ta ble 2. Syn th esis of th e Isoben zop yr yliu m Sa lts 3
entry
R1
R2
X
yield/% a
a
b
c
d
e
f
g
h
i
j
k
l
m
n
o
p
NMe2
TMS
H
Ph
p-tol
p-OC10
Ph
p-tol
p-OC10
TMS
Ph
p-tol
p-OC10
Ph
Ph
p-tol
n-Bu
TfO
0b
0b
63
64
50
OEt
H
BF4
TfO
66c (83)d
88c (95)d
0 (67)d
0b
>99b
>99b
>95b
74
66
84
Ph
TfO
BF4
TfO
TfO
0
a
b
Isolated and analytically pure. In situ 1H NMR observation
precluded isolation and characterization in pure form, but
full characterization of the hydrolyzed products agreed
with data for 5a and 5b found in the literature. Similarly,
attempts to precipitate compound 3h resulted in immedi-
ate hydrolysis to 5c. Unlike other functionalities studied,
the ethyl esters 2g-i required the use of HBF4 to induce
cyclization: treatment of 2h with TfOH led to a signifi-
of the transient intermediate. c Isolated alongside hydrolysis
product 5a ,b, yield determined by 1H NMR integration. Isolated
d
yield of 5a -c after complete hydrolysis.
NMR, the two 85-100 ppm ethynyl carbon resonances
disappeared, and a new resonance corresponding to the
former carbonyl carbon (C1 of 3) appeared at 170-180
ppm. A new aromatic singlet (Ha of 3) appeared in the
1H spectra upon cyclization but did not appear during
TfOD-induced cyclizations.
(9) (a) Kleinpeter, E.; Spitzner, R.; Schroth, W. Magn. Reson. Chem.
1987, 25, 688-695. (b) Kleinpeter, E.; Spitzner, R.; Schroth, W.;
Pihlaja, K.; Mattinen, J . Magn. Reson. Chem. 1988, 26, 707-713.
(10) Please see the Supporting Information for complete experimen-
tal and structural data.
The triflate salts 3c-e (R1 ) NMe2) precipitated
readily from diethyl ether and maintained stability under

Notes
J . Org. Chem., Vol. 64, No. 17, 1999 6501
Ta ble 3. Isoqu in olin es 4 fr om Am in a tion of P yr yliu m
Sa lts 3
(for R1 ) OEt) discussed earlier that reduced their full
pyrylium character and inhibited their reactivities as
pyrylium compounds. We found that these compounds
underwent competitive transformation into the corre-
sponding free amino isoquinolines 6. The precursors to
entry
R1
R2
Ph
X
method
yield/%a
a
b
c
d
e
f
NMe2
TfO
A
B
A
B
A
A
A
A
B
A
22 (32)
30 (45)
0 (52)
23 (11)b
21 (66)
74
p-tol
p-OC10
Ph
p-tol
Ph
OEt
H
BF4
TfO
g
h
i
p-tol
p-OC10
Ph
67
65
38
Ph
TfO
j
p-tol
67
a
b
Values in parentheses refer to 6. In addition to 30% of
hydrolysis product 5a (GC-MS determination).
4f-j (R1 ) H, Ph) have more pyrylium character and
therefore readily reacted with ammonia in accordance
with literature precedents.15 We anticipate that this
methodology should prove useful for the development of
more convergent syntheses of aryl isoquinolines.
In closing, we have shown that the acid-induced
electrophilic cyclizations of alkynes with carbonyl oxygens
provide a new and efficient route to pyrylium salts and
their isoquinoline analogues. Future work shall focus on
expanding our methodology to other heteroatomic sys-
tems and to polymeric systems in order to open new
avenues of postpolymerization modification.
cant amount of isocoumarin formation. The triflate salts
3j-l (R1 ) H) did not precipitate from the reaction
1
mixture, so we relied on in situ H NMR to characterize
these transient intermediates using both TfOH and TfOD
prior to further synthetic manipulations. Alkynes 2k and
2l cyclized quantitatively while a second undetermined
side-product competitively formed during the cyclization
of 2m ; again, a possible result of acid-induced aryl ether
cleavage.7
Due to the charge localization found in the amino
compounds and the problematic isolations of the 1-protio
and ethoxy salts, we set out to study the more traditional
pyrylium systems 3m -p (R1 ) Ph). Upon cyclization, the
observed downfield proton singlet for Ha at 8.8 ppm
indicates the greater expected degree of aromaticity
within these systems. Relative to the benzophenone
carbonyl 13C NMR resonance, C1 of 3 shifted upfield by
20 ppm, showing less carbonyl character: carbon NMR
data for 3n correlated well with literature values.11 While
3n fluoresced weakly in comparison to the exocyclic
amine compounds, it also displayed a significant Stokes
shift upon emission.
As a further structural proof and a demonstration of
utility, we used anhydrous ammonia to transform the
isobenzopyrylium salts 3 into the corresponding iso-
quinolines 4.12 Many syntheses utilize a Bischler-Napi-
eralski cyclization to construct the isoquinoid ring sys-
tem,13 but using this procedure for the construction of
3-arylisoquinoline ring systems gives rise to competitive
retro-Ritter stilbenic side products.14 Investigations to-
ward an efficient methodology led to the conclusion that
exposure of a triflate salt generated in situ (method A)
and an isolation-exposure protocol (method B) provided
comparable yields, as outlined in Table 3. Thus, method
A serves as an attractive one-pot synthetic strategy for
constructing isoquinoline ring systems. The poor yields
for compounds 4a -e may result from the exocyclic charge
localization (for R1 ) NMe2) or the hydrolytic instability
Exp er im en ta l Section
Gen er a l. All synthetic manipulations were performed under
an argon atmosphere using standard Schlenk techniques unless
otherwise noted. All chemicals were of reagent grade; anhydrous
methylene chloride was purchased from Aldrich and used
without further purification. Column chromatography was
performed using Baker 40 µm silica gel. All organic extracts were
dried over MgSO4 and filtered prior to removal with a rotary
evaporator. NMR chemical shifts are referenced to CHCl3/TMS
(7.26 ppm for 1H, 77.23 ppm for 13C) or CD2HCN (1.94 ppm for
1H, 1.39 ppm for 13C). High-resolution mass spectra were
obtained at the MIT Department of Chemistry Instrumentation
Facility (DCIF) using a peak matching protocol to determine the
mass and error range of the molecular ion; FAB spectra were
obtained using a 3-nitrobenzyl alcohol matrix. Fluorescence
measurements were recorded on a SPEX Fluorolog-τ2 fluorim-
eter with
a 450 W xenon lamp. Elemental analyses were
obtained at Desert Analytics (Tucson, AZ). Melting points are
uncorrected.
Isoben zoyr yliu m Sa lts 3: Rep r esen ta tive P r oced u r e.
One equivalent of an alkyne precursor 2 was added to a dry
Schlenk flask and placed under argon. A 0.005 M solution of
the alkyne in methylene chloride was prepared and stirred
vigorously as 20 equiv of the acid (neat trifluoromethanesulfonic
acid unless otherwise noted) was added dropwise. The reaction
stirred at room temperature for 0.5-1.5 h at which point the
salts were precipitated with diethyl ether or used for amination
studies as described individually below. For NMR studies,
chloroform-d (and CF3SO3D when specified) was used in lieu of
methylene chloride.
1-(N,N-Dim eth yla m in o)-3-p h en ylisoben zop yr yliu m Tr i-
flu or om eth a n esu lfon a te (3c). Starting from 101 mg of 2c
(0.406 mmol), the reaction stirred for 1 h at which point solvent
volume was reduced in vacuo by approximately 50%. 3c was
precipitated with diethyl ether followed by filtration and repre-
cipitation from MeCN/CH2Cl2 to provide a greenish-yellow fluffy
solid (102 mg, 0.254 mmol, 63%) (mp 204.5-206.0 °C). 1H NMR
(500 MHz, CD3CN) δ: 8.44 (d, 1H, J ) 8.5 Hz), 8.03 (t, 1H, J )
8.0 Hz), 7.96 (m, 2H), 7.88 (d, 1H, J ) 8.0 Hz), 7.77 (t, 1H, J )
8.5 Hz), 7.63 (s, 1H), 7.61 (m, 3H), 3.87 (s, 3H), 3.69 (s, 3H). 13C
NMR (125 MHz, CD3CN) δ: 165.3, 152.5, 139.2, 138.4, 132.3,
131.3, 130.8, 130.5, 130.4, 129.0, 126.5, 122.2 (q, 319 Hz), 116.3,
(11) Saba, A.; Sib, F. S.; Aycard, J .-P. Spectrosc. Lett. 1993, 26, 491-
496.
(12) During preparation of this manuscript, we found a recently
published procedure which effected cyclizations of o-ethynylpyridin-
ecarbaldehydes to the corresponding naphthyridines upon exposure
to ethanolic ammonia at 80 °C in a sealed tube: Numata, A.; Kondo,
Y.; Sakamoto, T. Synthesis 1999, 306-311. Applying this protocol to
2k gave a 37% crude yield of 4f.
(13) For a discussion of the Bischler-Napieralski reaction and other
related synthetic strategies, see: Kametani, T.; Fukumoto, K. In
Isoquinolines. Grethe, G., Ed.; J ohn Wiley & Sons: New York, 1981;
Part I, pp 139-274.
(14) (a) Fodor, G.; Nagubandi, S. Tetrahedron 1980, 36, 1279-1300.
(b) Larsen, R. D.; Reamer, R. A.; Corley, E. G.; Davis, P.; Grabowski,
E. J . J .; Reider, P. J .; Shinkai, I. J . Org. Chem. 1991, 56, 6034-6038
and references therein.
(15) (a) Baeyer, A.; Piccard, J . Ann. Chem. 1911, 384, 208-224. (b)
Blount, B. K.; Robinson, R. J . Chem. Soc. 1933, 555-557.

6502 J . Org. Chem., Vol. 64, No. 17, 1999
Notes
106.6, 46.0, 43.6. FT-IR (KBr): ν/cm-1: 1661, 1610, 1484, 1420,
1266 (vs). UV-vis (CH3CN) λmax/nm (log ꢀ): 271 (4.38), 303 (s,
4.20), 370 (3.94). Emission (CH3CN) λmax/nm: 474. HR-MS
Hz), 7.93 (m, 3H), 7.47 (d, 2H, J ) 8.0 Hz), 5.25 (q, 2H, J ) 7.0
Hz), 2.46 (s, 3H), 1.73 (t, 3H, J ) 7.0 Hz).
3-P h en ylisoben zop yr yliu m Tr iflu or om eth a n esu lfon a te
(3j). Generated in situ from 2k (3.2 mg, 0.0155 mmol) in 2 mL
of chloroform-d to provide a greenish-yellow fluorescent inter-
mediate which could not be isolated but was observed by 1H
NMR approximately 1 h into the reaction. Further structural
proof was obtained after exposure to ammonia: characterization
data for 4f was consistent with literature values and can be
found in the Supporting Information. 1H NMR (500 MHz, CDCl3)
δ: 10.18 (s, 1H), 8.67 (s, 1H), 8.57 (d, 1H, J ) 8.5 Hz), 8.54 (t,
1H, J ) 8.5 Hz), 8.29 (d, 1H, J 8.5 Hz), 8.16 (m, 3H), 7.78 (t,
1H, J ) 7.0 Hz), 7.71 (t, 2H, J ) 7.5 Hz). 4-Deu ter io-3-
ph en ylisoben zopyr yliu m Tr iflu or om eth an esu lfon ate. Gen-
erated as 3j using TfOH-d. 1H NMR (500 MHz, CDCl3) δ: 10.19
(s, 1H), 8.58 (d, 1H, J ) 8.5 Hz), 8.54 (td, 1H, J ) 8.0, 1.0 Hz),
8.29 (d, 1H, J ) 8.5 Hz), 8.16 (m, 3H), 7.78 (t, 1H, J ) 7.5 Hz),
7.71 (t, 2H, J ) 8.0 Hz).
3-(4-Meth ylph en yl)isoben zopyr yliu m Tr iflu or om eth an e-
su lfon a te (3k ). Generated in situ from 2l (3.4 mg, 0.0154 mmol)
in 2 mL of chloroform-d to provide an intensely yellow fluores-
cent intermediate which could not be isolated but was observed
by 1H NMR approximately 1 h into the reaction. Further
structural proof was obtained after exposure to ammonia:
characterization data for 4g was consistent with literature
values and can be found in the Supporting Information. 1H NMR
(500 MHz, CDCl3) δ: 10.11 (s, 1H), 8.60 (s, 1H), 8.52 (d, 1H, J
) 8.5 Hz), 8.49 (td, 1H, J ) 8.5, 1.0 Hz), 8.24 (d, 1H, J ) 8.5
Hz), 8.11 (t, 1H, J ) 7.0 Hz), 8.04 (d, 2H, J ) 8.5 Hz), 7.51 (d,
2H, J ) 8.0 Hz), 2.53 (s, 3H). 4-Deu ter io-3-(4-m eth ylp h en yl)-
isoben zop yr yliu m Tr iflu or om eth a n esu lfon a te. Generated
as 3k using TfOH-d. 1H NMR (500 MHz, CDCl3) δ: 10.12 (s,
1H), 8.52 (d, 1H, J ) 8.0 Hz), 8.49 (t, 1H, J ) 7.0 Hz), 8.24 (d,
1H, J ) 8.5 Hz), 8.12 (t, 1H, J ) 8.0 Hz), 8.04 (d, 2H, J ) 8.5
Hz), 7.51 (d, 2H, J ) 7.5 Hz), 2.53 (s, 3H).
(EI): found m/z ) 250.1226 ( 0.0007 (M+); calcd for C17H16
-
NO+: 250.1232. HR-MS [FAB (-)]: found m/z ) 148.9522 (
0.0005 (M-); calcd for CF3SO3
: 148.9520. Anal. Calcd for
-
C
18H16F3NO4S: C, 54.13; H, 4.04; N, 3.51. Found: C, 53.90; H,
3.91; N, 3.75.
1-(N,N-Dim eth yla m in o)-3-(4-m eth ylp h en yl)isoben zop y-
r yliu m Tr iflu or om eth a n e su lfon a te (3d ). Starting from 103
mg of 2d (0.390 mmol), the reaction stirred for 1 h at which point
solvent volume was reduced in vacuo by approximately 50%. 3d
was precipitated with diethyl ether followed by filtration and
reprecipitation from MeCN/CH2Cl2 to provide a greenish-yellow
fluffy solid (104 mg, 0.251 mmol, 64%) (mp 208-209 °C). 1H
NMR (500 MHz, CD3CN) δ: 8.43 (d, 1H, J ) 8.5 Hz), 8.01 (t,
1H, J ) 7.5 Hz), 7.85 (m, 2H), 7.75 (t, 1H, J ) 8.0 Hz), 7.57 (s,
1H), 7.41 (d, 2H, J ) 7.5 Hz), 3.86 (s, 3H), 3.67 (s, 3H), 2.43 (s,
3H). 13C NMR (125 MHz, CD3CN) δ: 165.2, 152.7, 143.1, 139.3,
138.26, 131.3, 131.0, 130.1, 128.8, 128.0, 126.4, 122.2 (q, J )
328 Hz), 116.1, 105.7, 46.0, 43.6, 21.6. FT-IR (KBr): ν/cm-1
:
1658, 1607, 1479, 1420, 1262 (s). UV-vis (CH3CN) λmax/nm (log
ꢀ): 306 (s, 4.28), 376 (3.95). Emission (CH3CN) λmax/nm: 487.
HR-MS (EI): found m/z ) 264.1385 ( 0.0009 (M+); calcd for
C18H18NO+: 264.1388. HR-MS [FAB (-)]: found m/z ) 148.9519
( 0.0005 (M-); calcd for CF3SO3-: 148.9520. Anal. Calcd for
C
19H18F3NO4S: C, 55.20; H, 4.39; N, 3.39. Found: C, 54.95; H,
4.20; N, 3.35.
3-(4-Decyloxyph en yl)-1-(N,N-dim eth ylam in o)isoben zopy-
r yliu m Tr iflu or om eth a n esu lfon a te (3e). Starting from 82 mg
of 2e (0.202 mmol), 3e was precipitated with diethyl ether
followed by filtration and reprecipitation from MeCN/CH2Cl2 to
provide a yellow fluffy solid (54 mg, 0.100 mmol, 50%) (mp
136.5-138 °C). 1H NMR (500 MHz, CD3CN) δ: 8.41 (d, 1H, J )
8.5 Hz), 7.99 (t, 1H, J ) 8.0 Hz), 7.87 (d, 2H, J ) 9.0 Hz), 7.82
(d, 1H, J ) 7.0 Hz), 7.72 (td, 1H, J ) 7.5, 1.0 Hz), 7.48 (s, 1H),
7.09 (d, 2H, J ) 9.0 Hz), 4.07 (t, 2H, J ) 6.5 Hz), 3.85 (s, 3H),
3.66 (s, 3H), 1.78 (quin, 2H, J ) 6.5 Hz), 1.46 (quin, 2H, J ) 6.5
Hz), 1.30 (m, 12H), 0.89 (t, 3H, J ) 7.0 Hz). 13C NMR (125 MHz,
CD3CN) δ: 165.3, 162.7, 152.9, 139.7, 138.3, 131.2, 129.8, 128.6,
128.3, 122.9, 122.2 (q, J ) 319 Hz), 116.3, 115.8, 104.8, 69.4,
46.0, 43.5, 32.7, 30.4, 30.3, 30.1, 29.8, 26.7, 23.5, 14.5. FT-IR
(KBr): ν/cm-1: 1656, 1604, 1516, 1481, 1260 (s). UV-vis (CH3-
CN) λmax/nm (log ꢀ): 239 (4.16), 273 (4.32), 313 (4.39), 387 (4.03).
Emission (CH3CN) λmax/nm: 527. HR-MS (EI): found m/z )
406.2736 ( 0.0012 (M+); calcd for C27H36NO2+: 406.2746. HR-
MS [FAB (-)]: found m/z ) 148.9522 ( 0.0005 (M-); calcd for
CF3SO3-: 148.9520. Anal. Calcd for C28H36F3NO5S: C, 60.52;
H, 6.53; N, 2.52. Found: C, 60.18; H, 6.54; N, 2.58.
3-(4-Decyloxyphenyl)isobenzopyrylium Trifluoromethane-
su lfon a te (3l). Generated in situ from 2m (5.3 mg, 0.0146
mmol) in 2 mL of chloroform-d to provide an intense burgandy
intermediate which could not be isolated but was observed by
1H NMR after 10 min (NMR data listed below), 60 min (3:1
mixture of products) and 4 d into the reaction (one product, no
evidence for alkoxy protons). Further structural proof was
obtained after exposure to ammonia: characterization data for
1
4h was consistent with the proposed isoquinoline structure. H
NMR (500 MHz, CDCl3) δ: 10.02 (s, 1H), 8.51 (s, 1H), 8.43 (m,
2H), 8.18 (d, 1H, J ) 7.5 Hz), 8.11 (d, 2H, J ) 9.0 Hz), 8.05 (t,
1H, J ) 8.5 Hz), 7.19 (d, 2H, J ) 9.0 Hz), 4.18 (t, 2H, J ) 6.5
Hz), 1.86 (quin, 2H, J ) 7.5 Hz), 1.48 (quin, 2H, J ) 7.5 Hz),
1.29 (bm, 12H), 0.88 (t, 3H, J ) 7.0 Hz).
1-Eth oxy-3-p h en ylisoben zop yr yliu m Tetr a flu or obor a te
(3f). Starting from 103 mg of 2g (0.412 mmol) and 2.5 mL of a
54% solution of HBF4 in diethyl ether (18 mmol), 3f was
precipitated with diethyl ether along side hydrolysis product 5a
to provide 136 mg of a pale yellow fluffy solid. The instability of
this compound prevented isolation in pure form, so peaks
attributed to 3f were assigned by comparison with a pure sample
of isocoumarin 5a . Literature values for 3-phenylisocoumarin
were consistent with those obtained for 5a and can be found in
1,3-Diph en ylisoben zopyr yliu m Tr iflu or om eth an esu lfon -
a te (3m ). Starting from 101 mg of 2n (0.358 mmol) and following
addition of diethyl ether, the solution was stored overnight at 0
°C. The resulting solids were filtered and washed with ether to
give 3m as an orange powder (114 mg, 0.264 mmol, 74%) (mp
189.5-190.0 °C). 1H NMR (500 MHz, CD3CN) δ: 8.80 (s, 1H),
8.68 (d, 1H, J ) 8.5 Hz), 8.46 (t, 1H, J ) 7.0 Hz), 8.34 (d, 1H, J
) 8.0 Hz), 8.23 (m, 4H), 8.09 (t, 1H, J ) 7.5 Hz), 7.99 (t, 1H, J
) 7.5 Hz), 7.87 (t, 2H, J ) 8.5 Hz), 7.73 (m, 3H). 13C NMR (125
MHz, CD3CN) δ: 182.2, 161.8, 145.1, 144.1, 136.6, 134.2, 134.1,
134.0, 133.7, 131.0 (2 Cs), 130.5, 130.3, 129.4, 127.9, 124.3, 122.2
(q, J ) 319 Hz), 116.5. FT-IR (KBr): ν/cm-1: 1621, 1541, 1499,
1417, 1272 (vs). UV-vis (CH3CN) λmax/nm (log ꢀ): 228 (4.22),
267 (4.44), 303 (s, 4.36), 441 (3.99). HR-MS (EI): found m/z )
283.1126 ( 0.0008 (M+); calcd for C21H15O+: 283.1123. HR-MS
[FAB (-)]: found m/z ) 148.9522 ( 0.0005 (M-); calcd for CF3-
SO3-: 148.9520. Anal. Calcd for C22H15F3O4S: C, 61.11; H, 3.50.
Found: C, 60.98; H, 3.45.
1
the Supporting Information. Using H NMR integration ratios,
1
0.272 mmol of 3f was obtained (66%). H NMR (500 MHz, CD3-
CN) δ: 8.54 (d, 1H, J ) 8.5 Hz), 8.29 (td, 1H, J ) 8.5, 1.0 Hz),
8.17 (s, 1H), 8.09 (d, 1H, J ) 8.0 Hz), 8.04 (m, 2H), 7.96 (td, 1H,
J ) 7.0, 1.0 Hz), 7.67 (m, 3H), 5.27 (q, 2H, J ) 7.0 Hz), 1.74 (t,
3H, J ) 7.0 Hz).
1-Eth oxy-3-(4-m eth ylph en yl)isoben zopyr yliu m Tetr aflu -
or obor a te (3g). Starting from 108 mg of 2h (0.409 mmol) and
1.15 mL of a 54% solution of HBF4 in diethyl ether (8.35 mmol),
3g was precipitated with diethyl ether along side hydrolysis
product 5b to provide 138 mg of a pale yellow fluffy solid. The
instability of this compound prevented isolation in pure form,
so peaks attributed to 3g were assigned by comparison with a
pure sample of isocoumarin 5b. Literature values for 3-(4-
methylphenyl)isocoumarin were consistent with those obtained
for 5b and can be found in the Supporting Information. Using
1H NMR integration ratios, 0.360 mmol of 3g was obtained
1,3-Dip h en ylisoben zop yr yliu m Tetr a flu or obor a te (3n ).11
Starting from 101 mg of 2n (0.358 mmol), 3n was precipitated
with diethyl ether followed by filtration to provide an orange
solid (88 mg, 0.237 mmol, 66%) [mp 241-242.5 °C (dec)]. 1H
NMR (500 MHz, CD3CN) δ: 8.80 (s, 1H), 8.68 (d, 1H, J ) 8.5
Hz), 8.46 (t, 1H, J ) 7.0 Hz), 8.34 (d, 1H, J ) 8.5 Hz), 8.23 (m,
4H), 8.09 (t, 1H, J ) 7.0 Hz), 7.99 (t, 1H, J ) 7.5 Hz), 7.87 (t,
2H, J ) 8.0 Hz), 7.73 (m, 3H). 13C NMR (125 MHz, CD3CN) δ:
182.2, 161.8, 145.1, 144.1, 136.6, 134.2, 134.1, 134.0, 133.7, 131.0
(2C), 130.5, 130.3, 129.4, 127.9, 124.3, 116.5. FT-IR (KBr):
1
(88%). H NMR (500 MHz, CD3CN) δ: 8.51 (d, 1H, J ) 8.0 Hz),
8.27 (td, 1H, J ) 8.0, 1.0 Hz), 8.10 (s, 1H), 8.06 (d, 1H, J ) 8.5

Notes
J . Org. Chem., Vol. 64, No. 17, 1999 6503
ν/cm-1: 1619, 1540, 1502, 1417, 1056 (vs). UV-vis (CH3CN) λmax
/
(M+); calcd for C18H18N2: 262.1470. Further elution with 3:1
hexane/ ethyl acetate afforded 1-a m in o-3-(4-m eth ylp h en yl)-
isoqu in olin e (6b) as a pale yellow oil which solidified upon
standing (13 mg, 0.054 mmol, 45%) (mp 105.5-106.5 °C). 1H
NMR (500 MHz, CDCl3) δ: 7.96 (d, 2H, J ) 8.5 Hz), 7.71 (m,
2H), 7.56 (t, 1H, J ) 7.5 Hz), 7.44 (s, 1H), 7.38 (t, 1H, J ) 7.0
Hz), 7.26 (d, 2H, J ) 8.0 Hz), 5.29 (bs, 2H), 2.39 (s, 3H). 13C
NMR (125 MHz, CDCl3) δ: 156.1, 149.8, 138.4, 138.2, 137.3,
130.3, 129.5, 127.6, 126.9, 125.8, 122.8, 117.0, 108.5, 21.5. FT-
IR (KBr) ν/cm-1: 3487, 3453, 3290, 1620, 1561, 1495, 1432. HR-
MS (EI): found m/z ) 234.1155 ( 0.0007 (M+); calcd for
C16H14N2: 234.1157.
1-Eth oxy-3-p h en ylisoqu in olin e (4d ).17 The salt 3f was
prepared from 106 mg of 2g (0.4235 mmol) by method A using
ethereal HBF4. The precipitate was filtered, washed with ether,
and immediately placed under argon. Using method B followed
by column chromatography (3:1 hexane/ methylene chloride)
provided 4d as a white oily solid (24.5 mg, 0.0298 mmol, 23%).
1H NMR (500 MHz, CDCl3) δ: 8.27 (d, 1H, J ) 8.0 Hz), 8.16 (d,
2H, J ) 7.5 Hz), 7.78 (d, 1H, J ) 8.0 Hz), 7.68 (s, 1H), 7.64 (t,
1H, J ) 7.0 Hz), 7.49 (m, 3H), 7.39 (t, 1H, J ) 7.5 Hz), 4.72 (q,
2H, J ) 7.0 Hz), 1.56 (t, 3H, J ) 7.0 Hz). 13C NMR (75 MHz,
CDCl3) δ: 160.2, 147.9, 139.7, 138.9, 130.6, 128.7, 128.4, 126.8,
126.7 (2C), 126.4, 124.4, 119.1, 110.3, 62.2, 15.0. FT-IR (KBr)
nm (log ꢀ): 302 (4.36), 440 (4.01). Emission (CH3CN) λmax/nm:
538 (very weak). HR-MS (EI): found m/z ) 283.1117 ( 0.0008
(M+); calcd for C21H15O+: 283.1123. HR-MS [FAB (-)]: found
m/z ) 87.0028 ( 0.0003 (M-); calcd for BF4-: 87.0029.
3-(4-Meth ylp h en yl)-1-p h en ylisoben zop yr yliu m Tr iflu o-
r om eth a n esu lfon a te (3o). Starting from 100 mg of 2o (0.338
mmol) and following addition of diethyl ether, the solution was
stored at 0 °C overnight. The precipitated solids were filtered
off and washed with ether to provide 3o as an orange solid (126
mg, 0.283 mmol, 84%) [mp 220.5-221.5 °C (sub)]. 1H NMR (500
MHz, CD3CN) δ: 8.76 (s, 1H), 8.66 (d, 1H, J ) 9.0 Hz), 8.45 (t,
1H, J ) 7.5 Hz), 8.32 (d, 1H, J ) 8.5 Hz), 8.23 (d, 2H, J ) 7.0
Hz), 8.14 (d, 2H, J ) 8.0 Hz), 8.08 (t, 1H, J ) 7.5 Hz), 8.00 (t,
1H, J ) 7.5 Hz), 7.88 (t, 2H, J ) 8.0 Hz), 7.55 (d, 2H, J ) 8.0
Hz), 2.51 (s, 3H). 13C NMR (125 MHz, CD3CN) δ: 181.6, 162.1,
145.6, 145.3, 143.9, 136.4, 133.8, 133.8, 133.6, 131.7, 131.0, 130.5,
129.3, 127.9, 127.5, 124.1, 122.2 (q, J ) 318 Hz), 115.9, 21.8.
FT-IR (KBr): ν/cm-1: 1621, 1540, 1499, 1418, 1265 (vs). UV-
vis (CH3CN) λmax/nm (log ꢀ): 233 (4.23), 271 (4.41), 304 (4.35),
329 (s), 452 (3.98). HR-MS (FAB): found m/z ) 297.1276 (
0.0009 (M+); calcd for C22H17O: 297.1279. HR-MS [FAB (-)]:
-
found m/z ) 148.9523 ( 0.0005 (M-); calcd for CF3SO3
:
148.9520. Anal. Calcd for C23H17F3O4S: C, 61.88; H, 3.84.
Found: C, 61.93; H, 3.73.
ν/cm-1
: 1626, 1574, 1500, 1378. HR-MS (EI): found m/z )
249.1157 ( 0.0007 (M+); calcd for C17H15NO: 249.1154. Gradu-
ally increasing the elution solvent polarity led to the isolation
of 43.6 mg of a solid containing primarily the isocoumarin 5a
(65% by GC-MS, 30% estimated overall yield). Further elution
provided 11 mg of 6a (0.047 mmol, 11%) as a yellowish solid.
Isoq u in olin es 4. R ep r esen t a t ive P r oced u r es. Met h od
A: The pyrylium salts 3 were prepared as described above at
which point anhydrous ammonia was bubbled through the
reaction mixture for 30-45 min, placed under a positive pressure
of ammonia and stirred for a total of 20 h. The reaction mixture
was washed with NaHCO3 (aq) and NaCl (aq). The organic layer
was separated, dried, and removed in vacuo to provide a crude
material which was purified on silica gel to yield the isoquino-
lines listed below.
1-Eth oxy-3-(4-m eth ylph en yl)isoqu in olin e (4e). Using 101.6
mg of 2h (0.3844 mmol) in method A with ethereal HBF4 in lieu
of TfOH followed by chromatography (2:1 hexane/methylene
chloride) provided 4e as a oily white solid (20.9 mg, 0.0794 mmol,
21%). Further elution with 4:1 hexane/ethyl acetate also pro-
vided 6b (59 mg, 0.252 mmol, 66%). 1H NMR (500 MHz, CDCl3)
δ: 8.25 (d, 1H, J ) 8.0 Hz), 8.05 (d, 2H, J ) 8.0 Hz), 7.76 (d,
1H, J ) 8.0 Hz), 7.63 (m, 2H), 7.48 (t, 1H, J ) 8.0 Hz), 7.28 (d,
2H, J ) 8.0 Hz), 4.71 (q, 2H, J ) 7.0 Hz), 2.42 (s, 3H), 1.55 (t,
3H, J ) 6.5 Hz). 13C NMR (125 MHz, CDCl3) δ: 160.2, 148.1,
139.1, 138.4, 137.0, 130.6, 129.5, 126.7 (2C), 126.2, 124.4, 119.1,
109.8, 62.1, 21.5, 14.9. FT-IR (KBr): ν/cm-1: 1626, 1576, 1411,
1377. HR-MS (EI): found m/z ) 263.1304 ( 0.0007 (M+); calcd
for C18H17NO: 263.1310.
Meth od B: The isolated salt 3 was placed under argon in a
dry Schlenk flask and brought to a concentration of 0.005 M in
methylene chloride. The suspension was stirred vigorously to
effect some dissolution, and anhydrous ammonia was bubbled
through the flask for 30-45 min. The system was placed under
a positive ammonia pressure and stirred for a total of 20 h.
Washing the organic phase as described for method A followed
by column chromatography provided the desired isoquinolines.
For further purification, the isoquinolines were taken up in
ether and precipitated as the hydrochloride salts upon addition
of 12 M HCl. Rinsing the solids twice with ether and a basic
workup [2 M KOH, NaHCO3, and NaCl (aq)] again provided the
isoquinolines which were pure by 1H NMR and GC-MS (96%+).
Reported yields are for products obtained after chromatography.
1-(N,N-Dim eth yla m in o)-3-p h en ylisoqu in olin e (4a ). Us-
ing 106 mg of 2c (0.425 mmol) in method A followed by column
chromatography (3:1 hexane/ ethyl acetate) provided 4a as a
yellow oil (24 mg, 0.095 mmol, 22%). 1H NMR (500 MHz, CDCl3)
δ: 8.19 (d, 2H, J ) 7.5 Hz), 8.14 (d, 1H, J ) 8.5 Hz), 7.79 (d,
1H, J ) 8.5 Hz), 7.65 (s, 1H), 7.58 (td, 1H, J ) 8.0, 1.0 Hz), 7.47
(m, 3H), 7.38 (t, 1H, J ) 7.5 Hz), 3.20 (s, 6H). 13C NMR (75 MHz,
CDCl3) δ: 161.4, 148.1, 140.0, 139.4, 129.6, 128.7, 128.3, 127.7,
126.8, 126.2, 125.4, 120.5, 110.3, 43.3. FT-IR (KBr) ν/cm-1: 1618,
1561, 1501, 1385, 1344. HR-MS (EI): found m/z ) 248.1309 (
0.0007 (M+); calcd for C17H16N2: 248.1313. Further elution with
2:1 hexane/ ethyl acetate provided 1-a m in o-3-p h en ylisoqu in o-
lin e (6a ) as a pale yellow solid (34 mg, 0.135 mmol, 32%) (mp
95.5-96.5 °C, lit.16 97.5-99 °C).
3-P h en ylisoqu in olin e (4f). Using 106 mg of 2k (0.515 mmol)
in method A followed by column chromatography (7.5:1 hexane/
ethyl acetate) provided 4f as yellow flakes (78 mg, 0.382 mmol,
74%). (mp 101-101.5 °C, lit.18 102.5-103.5 °C).
3-(4-Meth ylp h en yl)isoqu in olin e (4g). Using 101 mg of 2l
(0.458 mmol) in method A followed by purification on silica gel
(5:1 hexane/ethyl acetate) provided 4g as a light brown solid (67
mg, 0.306 mmol, 67%). (mp 74-75 °C, lit.18 76-76.5 °C).
3-(4-Decyloxyp h en yl)isoqu in olin e (4h ). Using 50 mg of
2m (0.138 mmol) in method A followed by column chromatog-
raphy (9:1 hexane/ethyl acetate) provided 4h as a light brown
solid (32 mg, 0.0891 mmol, 65%). Further purification as
described above gave 16 mg of 4h as a white solid (0.043 mmol,
31%) (mp 78.5-79 °C). 1H NMR (500 MHz, CDCl3) δ: 9.30 (s,
1H), 8.07, d, 2H, J ) 8.5 Hz), 7.99 (s, 1H), 7.97 (d, 1H, J ) 8.5
Hz), 7.84 (d, 1H, J ) 8.0 Hz), 7.67 (t, 1H, J ) 7.0 Hz), 7.55 (t,
1H, J ) 7.5 Hz), 7.03 (d, 2H, J ) 8.5 Hz), 4.03 (t, 2H, J ) 7.0
Hz), 1.82 (quin, 2H, J ) 6.5 Hz), 1.48 (quin, 2H, J ) 6.5 Hz),
1.28 (bm, 12H), 0.89 (t, 3H, J ) 6.5 Hz). 13C NMR (125 MHz,
CDCl3) δ: 160.0, 152.5, 151.4, 137.0, 132.2, 130.6, 128.4, 127.8,
127.6, 127.0, 126.8, 115.5, 115.0, 68.3, 32.1, 29.82, 29.79, 29.66,
29.56, 29.52, 26.3, 22.9, 14.4. FT-IR (KBr): ν/cm-1: 1625, 1605,
1512, 1446, 1251. HR-MS (EI): found m/z ) 361.2402 ( 0.0010
(M+); calcd for C25H31NO: 361.2406.
1-(N,N-Dim e t h yla m in o)-3-(4-m e t h ylp h e n yl)isoq u in o-
lin e (4b). Using 50 mg of 3d (0.120 mmol) in method B followed
by column chromatography (2:1 hexane/methylene chloride)
provided 4b as a yellow oil (9 mg, 0.036 mmol, 30%). 1H NMR
(500 MHz, CDCl3) δ: 8.12 (d, 1H, J ) 8.0 Hz), 8.08 (d, 2H, J )
8.0 Hz), 7.76 (d, 1H, J ) 8.0 Hz), 7.61 (s, 1H), 7.56 (td, 1H, J )
7.0, 1.0 Hz), 7.43 (td, 1H, J ) 7.0, 1.0 Hz), 7.28 (d, 2H, J ) 8.0
Hz), 3.19 (s, 6H), 2.41 (s, 3H). 13C NMR (125 MHz, CDCl3) δ:
161.4, 148.3, 139.6, 138.2, 137.3, 129.6, 129.5, 127.6, 126.7, 126.3,
125.3, 120.4, 109.9, 43.2, 21.5. FT-IR (KBr): ν/cm-1: 1616, 1561,
1515, 1497, 1385. HR-MS (EI): found m/z ) 262.1464 ( 0.0008
1,3-Dip h en ylisoqu in olin e (4i). Using 80 mg of 3m (0.186
mmol) in method B followed by column chromatography (1:1
(17) Kirby, G. W.; Tan, S. L.; Uff, B. C. J . Chem. Soc., Perkin Trans.
1 1979, 266-269.
(16) Casey, M.; Moody, C. J .; Rees, C. W. J . Chem. Soc., Perkin
Trans. 1 1984, 1933-1941.
(18) Bradsher, C. K.; Wallis, T. G. J . Org. Chem. 1978, 43, 3817-
3820.

6504 J . Org. Chem., Vol. 64, No. 17, 1999
Notes
hexane/methylene chloride) provided 4i as an oily opaque solid
(19.8 mg, 0.0704 mmol, 38%) (mp 73-74.5 °C, lit.19 71-73 °C).
3-(4-Meth ylp h en yl)-1-p h en ylisoqu in olin e (4j). Using 100
mg of 2o (0.337 mmol) in method A followed by column
chromatography (2:2 hexane/methylene chloride) provided 4j as
a pale orange solid (67 mg, 0.226 mmol, 67%) (mp 116-117 °C).
1H NMR (500 MHz, CDCl3) δ: 8.12 (d, 3H, J ) 8.0 Hz), 8.04 (s,
1H), 7.92 (d, 1H, J ) 8.5 Hz), 7.81 (d, 2H, J ) 7.5 Hz), 7.67 (t,
1H, J ) 7.0 Hz), 7.52 (m, 4H), 7.30 (d, 2H, J ) 7.5 Hz), 2.42 (s,
3H). 13C NMR (125 MHz, CDCl3) δ: 160.4, 150.4, 140.1, 138.5,
138.0, 137.0, 130.4, 130.1, 129.6, 128.7, 128.5, 127.71, 127.57,
2H, J ) 7.5 Hz), 1.47 (quin, 2H, J ) 7.5 Hz), 1.28 (bm, 12H),
0.89 (t, 3H, J ) 6.5 Hz). 13C NMR (125 MHz, CDCl3) δ: 159.7,
156.0, 149.4, 138.6, 132.3, 130.5, 128.2, 127.6, 125.8, 122.8, 116.8,
114.8, 108.0, 68.3, 32.1, 29.81, 29.79, 29.66, 29.56, 29.51, 26.3,
22.9, 14.36. FT-IR (KBr) ν/cm-1: 3466, 3393, 3347, 1605, 1563,
1513, 1420. HR-MS (EI): found m/z ) 376.2518 ( 0.0011 (M+);
calcd for C25H32N2O: 376.2515.
Ack n ow led gm en t. The authors thank Prof. Keiki
Kishikawa for supplying p-decyloxyphenyl acetylene
and Drs. William B. Davis and Hsiu-Fu Hsu for X-ray
data collection/refinement and helpful discussions, re-
spectively. We greatly appreciate generous financial
support from the Office of Naval Research and the
Defense Advanced Research Projects Agency.
127.1, 126.9, 125.8, 115.4, 21.5. FT-IR (KBr): ν/cm-1
: 1621,
1562, 1516, 1445, 1386. HR-MS (EI): found m/z ) 295.1356 (
0.0009 (M+); calcd for C22H17N: 295.1361.
1-Am in o-3-(4-d ecyloxyp h en yl)isoqu in olin e (6c). Using 2e
(49 mg, 0.121 mmol) in method A followed by column chroma-
tography (4:1 hexane/ethyl acetate) provided 6c as a clear oil
(25 mg, 0.0675 mmol, 52%). Purification as described above
provided 13 mg of 6c as a white solid (0.033 mmol, 27%) (mp
66-67.5 °C). 1H NMR (500 MHz, CDCl3) δ: 7.99 (d, 2H, J ) 8.5
Hz), 7.79 (d, 1H, J ) 8.0 Hz), 7.73 (d, 1H, J ) 8.0 Hz), 7.60 (t,
1H, J ) 7.5 Hz), 7.43 (t, 1H, J ) 7.5 Hz), 7.41 (s, 1H), 6.98 (d,
2H, J ) 8.5 Hz), 5.26 (s, 2H), 4.01 (t, 2H, J ) 6.5 Hz), 1.81 (quin,
Su p p or tin g In for m a tion Ava ila ble: Full experimental
details and characterization data for 2a -p and 5a -c; ad-
ditional characterization data for literature compounds 4f, 4g,
4i, and 6a ; copies of 1H and 13C spectra of all new compounds;
ORTEP diagram and X-ray crystallographic data for 3d . This
material is available free of charge via the Internet at
http://pubs.acs.org.
(19) Ford, A.; Sinn, E.; Woodward, S. J . Chem. Soc., Perkin Trans.
1 1997, 927-934.
J O990810X