An efficient synthesis of substituted quinolines

Article abstract of DOI:10.1055/s-2001-15221

The addition of substituted anilines to "vinamidinium" bis-tetrafluoroborate salt 1 [2-dimethylaminomethylene-1,3-bis(dimethylimmonio)propane bis-tetrafluoroborate], followed by cyclization of the resulting imino-eneamine salt and hydrolysis of the masked aldehydes 2, provide the corresponding 3-formyl quinolines 3. While the condensation of both 1 and its analogous bis-perchlorate salt and amidines are known to provide pyrimidines, we believe this is the first example of a quinoline annulation sequence with "vinamidinium" bis-tetrafluoroborate salt 1 and anilines.

Full text of DOI:10.1055/s-2001-15221

PAPER
1351
An Efficient Synthesis of Substituted Quinolines
An
E
fficient Synth
o
esis of Subst
r
ituted Q
m
uinolines a J. Tom,* Elizabeth M. Ruel
Pfizer Global Research and Development-Groton, Chemical Research and Development, Eastern Point Road, Groton, Connecticut, 06340,
USA
Fax +1(860)4413630; E-mail: Norma_J_Tom@groton.pfizer.com
Received 26 October 2000; revised 13 March 2001
O
OH
Abstract: The addition of substituted anilines to “vinamidinium”
R1
bis-tetrafluoroborate salt
1
[2-dimethylaminomethylene-1,3-
R1
R
OH
+
O
X
bis(dimethylimmonio)propane bis-tetrafluoroborate], followed by
cyclization of the resulting imino-eneamine salt and hydrolysis of
the masked aldehydes 2, provide the corresponding 3-formyl quin-
olines 3. While the condensation of both 1 and its analogous bis-
perchlorate salt and amidines are known to provide pyrimidines, we
believe this is the first example of a quinoline annulation sequence
with “vinamidinium” bis-tetrafluoroborate salt 1 and anilines.
X
NH2
N
R
Scheme 3
The Combes4 (Scheme 4), Skraup5 (Scheme 5), and
Doebner–Miller6 (Scheme 6) quinoline syntheses were
also reported in the late 1800s. The Combes method in-
volves heating an aniline with acetylacetone. The Skraup
and Doebner–Miller syntheses are very similar. The
former involves heating an aniline with acrolein, generat-
ed in situ from glycerol and a strong acid, and the latter
method is based on generating a substituted acrolein inter-
mediate. Both reactions also require an oxidant. Although
subsequent work on these methods has extended the scope
of these reactions, the substitution patterns that can be ob-
tained on the product quinolines is still limited. Other ma-
jor limitations are the high temperatures (>250 °C) and
highly acidic conditions that are required.
Key words: anilines, condensation, cyclizations, quinolines, “vina-
midinium” bis-tetrafluoroborate salt
The preparation of quinolines has been known since the
late 1800s. The Friedländer quinoline synthesis1 can be
defined as a condensation followed by cyclodehydration
of a substituted o-amino aromatic aldehyde or ketone with
another carbonyl compound containing a reactive -meth-
ylene group (Scheme 1). Although it does not require ca-
talysis, the Friedländer synthesis can be acid- or base-
catalyzed. The Pfitzinger reaction2 (Scheme 2) and the
Niemantowski reaction3 (Scheme 3) are considered exten-
sions of the Friedländer synthesis differing only in the
starting materials. Some of the restrictions of these three
methods involve the substitution pattern on the available
starting materials and thus, limits the functional groups on
the product quinoline, and high temperatures in some cas-
es.
Me
O
Me
X
+
X
O
NH2
N
Me
Me
Scheme 4
O
R
R2
R2
R1
O
CHO
R
+
X
X
+
X
X
R1
NH2
N
NH2
N
Scheme 1
Scheme 5
O
R2
CO2H
N
O
R1
R1
R
R1
R
CO H
R1
O
2
+
R2
X
X
X
X
+
NH2
NH2
R
N
R
Scheme 2
Scheme 6
There has been a report of “vinamidinium” mono-per-
chlorate salts7 and a report of a synthetic equivalent of “vi-
namidinium” type salts8 undergoing condensation and
intramolecular cyclization with anilines to provide 3-sub-
stituted quinolines. The substitution has been limited to
Synthesis 2001, No. 9, 29 06 2001. Article Identifier:
1437-210X,E;2001,0,09,1351,1355,ftx,en;M03000SS.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0039-7881

1352
N. J. Tom, E. M. Ruel
PAPER
alkyl, aryl, halogen, or ether functionalities at the 3-posi- provided the desired quinolines 7 and 8. The major by-
tion. This limitation is due in part to the technology avail- product of the reaction, dialdehyde 9, results from incom-
able to synthesize vinamidinium salts.9 Vinamidinium plete cyclization and subsequent hydrolysis of the imino-
salts have also been used to synthesize quinolines via a eneamine salt 4.
modified Friedländer synthesis.10 The preparation of more
highly substituted quinolines from -methylene ketones
R4
via a “vinamidinium” type mechanism11 has also been re-
R3
R2
R5
ported.
CHO
CHO
N
H
As part of a drug development program, we recently re-
quired access to a short and efficient synthesis of 3-formyl
substituted quinolines. This paper reports a mild method
for the synthesis of substituted quinolines. Condensation
and cyclization of a functionalized aniline with “vinami-
dinium” bis-tetrafluoroborate salt 1, followed by hydroly-
sis of the dimethyl imino group of the intermediate
quinoline 2 affords the 3-formyl quinoline 3 with the
functionality from the starting aniline mapping to the
quinoline ring (Scheme 7). This paper will discuss the
scope of this reaction.
R1
9
HCl
THF
N
2BF4
R4
R4
N
N
R3
R5
R3
R2
R5
2BF4
1
R2
N
H
N
NH2
R1
R1
N
4
N
R4
2BF4
R3
R2
R5
N
N
R4
N
N
N
BF4
BF4
R3
1
+
X
X
N
R2
N
NH2
2
R1
5
N
BF4
H
6
HCl
THF
HCl
THF
CHO
X
R4
N
R4
R3
R2
R5
N
3
R3
CHO
Scheme 7
R2
N
R1
The bis-tetrafluoroborate salt 1 was prepared according to
the literature.12,13 The analogous bis-perchlorate salt has
been used for pyrimidine syntheses.14 Concerns with the
potential thermal characteristics and the shock sensitivity
of the bis-perchlorate salt led co-workers to study the ma-
terial by calorimetry. The bis-perchlorate salt was found
to be a high energy and shock sensitive material.15 Recent-
ly, it was demonstrated that the lower energy bis-tetraflu-
oroborate salt 1 was as effective as the bis-perchlorate salt
for pyrimidine syntheses.15 However, the use of 1 as a
starting material has not been demonstrated for the syn-
thesis of quinolines.
7
CHO
8
Scheme 8
As shown in the Table, the quinoline annulation sequence
worked best when R2 had an electron-donating substitu-
ent. The electron-donating group ortho or para to the site
of cyclization facilitates the ring-closing step. The dialde-
hyde 9 is seen with substrates where the cyclization step
is sluggish (entries d–f, i, j, l, q–t). The ratios of products
of this reaction can be improved by using acetic acid or a
higher boiling alcohol such as butanol as the solvent (en-
tries g and h). It appears to be the higher temperature that
is the major factor in the cyclization step and not the acid
catalysis. The dialdehyde 9 is obtained when the reaction
is run in acetic acid at 78 °C (entry e) in the same ratio that
is observed when ethanol is the solvent (entry d). The ra-
tio is even worse in trifluoroethanol (entry f). However,
the overall yields tend to be lower due in part to greater
decomposition of the vinamidinium salt, and to a certain
extent, the product, at the higher temperature (entries g
We were pleased to find that condensation of substituted
anilines and “vinamidinium” bis-tetrafluoroborate salt 1
did indeed provide the desired quinolines, generally in
good to excellent yields. The reactions were generally
conducted by heating the reagents in ethanol at reflux for
12–48 hours, first to provide the imino-eneamine salt 4
(Scheme 8), followed by cyclization to afford the regio-
isomeric quinoline intermediates 5 and 6. Subsequent hy-
drolysis with 1 N HCl in THF at room temperature, then
Synthesis 2001, No. 9, 1351–1355 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
An Efficient Synthesis of Substituted Quinolines
1353
and h). The unsubstituted aniline (entry r) provides only The regioselectivity of this reaction appears to be deter-
trace amounts of the desired quinoline in refluxing etha- mined mainly by electronic considerations. Most of the
nol. In refluxing acetic acid after 48 hours (entry s), the substrates show high para selectivity due to the strong
product is observed in about a 1:1 ratio with dialdehyde 9. para-directing nature of the substituents at R2. When there
Generally, the product and the dialdehyde side product is substitution at R4, then the regioselectivity is deter-
were inseparable. Substrates with an ortho or para elec- mined by the combination of electronic factors, as well as
tron-donating group as well as an electron-withdrawing steric considerations. In entry p, the Cl at R4 deactivates
group do, in fact, afford the desired quinolines, albeit in the ortho and para position (ortho much more strongly
lower yields (entry p), as well as lower ratios of prod- than para) and the NH2 activates ortho and para, thus the
uct:dialdehyde 9 (entry q). The cyclization step for a sub- only regioisomer formed is 8. In entry q, the steric consid-
strate with an electron-donating group at R3 only is also erations of the methoxy group versus the trifluoromethyl
problematic. In refluxing acetic acid after 48 hours (entry group and the deactivating nature of the trifluoromethyl
t), the product is observed in a ratio of about 1:2 with di- group are important in determining the ratio of regioiso-
aldehyde 9.
mers.
In summary, we have found that “vinamidinium” bis-tet-
rafluoroborate salt 1 and anilines undergo an annulation
reaction to provide 3-formyl quinolines under mild condi-
tions. The reaction proceeds with high regioselectivity
and good to excellent yields in most cases.
Table Formation of Quinolines
Entry
Substrate (R1 = R5 = H)
Yield (%) Ratio of
(7:8:9)
7:8:9a
15:1:0
1:0:0
a
b
c
R2 = OMe, R3 = R4 = H
R2 = AcNH, R3 = R4 = H
R2 = NMe2, R3 = R4 = H
R2 = Me, R3 = R4 = H
R2 = Me, R3 = R4 = H
R2 = Me, R3 = R4 = H
R2 = Me, R3 = R4 = H
R2 = Me, R3 = R4 = H
R2 = Ph, R3 = R4 = H
R2 = Ph, R3 = R4 = H
R2 = OH, R3 = R4 = H
R2 = Cl, R3 = R4 = H
93
Unless otherwise noted, starting materials were obtained from com-
mercial suppliers and used without further purification. Flash col-
umn chromatography was carried out with J.T.Baker 40 m silica
gel according to the method of Still.16 TLC was performed with EM
Separations Technology silica gel F254. Melting points were mea-
sured in open capillary tubes and are uncorrected.
87
96
1:0:0
d
e
~80–90
~80–90b
~80–90c
71d
1:0:2.5
1:0:2.5
1:0:6
Quinolines 7, 8; General Procedure
f
A solution of the appropriate aniline (1 equiv) and “vinamidinium”
bis-tetrafluoroborate salt 1 (1.5–3 equiv) in EtOH, AcOH, or n-bu-
tanol (25 vol) was heated at reflux for 3–24 h. For highly activated
systems, lower equivalents of 1 and shorter reaction times are ade-
quate for driving the reactions to completion. After cooling to r.t.,
the solvent was removed by rotary evaporation. THF (15 vol) and
1 N HCL (15 vol) were added to the residue and the mixture was
stirred at r.t. for 2 h. The reaction mixture was neutralized with sat.
NaHCO3 solution (25 vol) and extracted with two 25-vol portions
of EtOAc. The combined organic layers were dried (Na2SO4) and
concentrated. The crude reaction mixture was purified by the meth-
od indicated to provide the product quinoline.
g
h
I
1:0:0
63e
1:0:0
52
1:0:1
J
k
L
m
n
o
p
q
r
43d
1:0:trace
20:1:0
5:1:12
1:0:0
64
72d
R2 = R4 = OMe, R3 = H
R2 = R3 = OMe, R4 = H
R2 = R3 = -OCH2O-, R4 = H
R2 = NH2, R3 = H, R4 = Cl
R2 = OMe, R3 = H, R4 = CF3
R2 = R3 = R4 = H
83
7-Methoxyquinoline-3-carbaldehyde (7a)17
Yield: 87%. Purified by flash column chromatography, gradient of
20% EtOAc–hexanes to 40% EtOAc–hexanes; mp 122–123°C.
1H NMR (300 MHz, DMSO-d6): = 10.2 (s, 1 H), 9.16 (d, 1 H,
J = 2.1 Hz), 8.79 (d, 1 H, J = 2.1 Hz), 8.06 (d, 1 H, J = 9.1 Hz), 7.45
(d, 1 H, J = 2.5 Hz), 7.33 (dd, 1 H, J = 9.1, 2.5 Hz), 3.93 (s, 3 H).
78
1:0:0
75
1:0:0
33
0:1:0
58d
1:1.5:3g
trace:0:1
1:0:1
13C NMR (100 MHz, DMSO-d6) = 192.6, 163.4, 152.7, 150.2,
140.1, 131.8, 127.5, 122.4, 121.2, 108.2, 56.5.
n/af
s
R2 = R3 = R4 = H
n/ad,f
n/ad,f
MS (APCI): m/z = 188.1 (M + H).
t
R2 = R4 = H, R3 = AcNH
1:0:2
5-Methoxyquinoline-3-carbaldehyde (8a)
Yield: 6%. Purified by flash column chromatography, gradient of
20% EtOAc–hexanes to 40% EtOAc–hexanes; mp 102–104°C.
1H NMR (400 MHz, DMSO-d6): = 10.2 (s, 1 H), 9.24 (d, 1 H,
J = 2.1 Hz), 9.05 (d, 1 H, J = 1.7 Hz), 7.87 (t, 1 H, J = 8.2 Hz), 7.66
(d, 1 H, J = 8.3 Hz), 7.18 (d, 1 H, J = 7.9 Hz), 4.03 (s, 3 H).
13C NMR (100 MHz, DMSO-d6): = 193.0, 156.5, 151.0, 149.5,
135.6, 134.1, 128.3, 121.5, 119.4, 106.9, 56.9.
a Ratios determined by 1H NMR spectroscopy.
b Reaction conducted in AcOH at 78 °C.
c Reaction conducted in CF3CH2OH at reflux.
d Reaction conducted in AcOH at reflux.
e Reaction conducted in butanol at reflux.
f Products were not isolated.
g Compound 8q was isolated cleanly, 7q and 9q were isolated as an
inseparable mixture.
MS (APCI): m/z = 188.1 (M + H).
Synthesis 2001, No. 9, 1351–1355 ISSN 0039-7881 © Thieme Stuttgart · New York

1354
N. J. Tom, E. M. Ruel
PAPER
HRMS (FAB): m/z Calcd for C11H9NO2: (MH)+ 188.0711. Found:
5-Hydroxyquinoline-3-carbaldehyde (8k)
188.0711.
Yield: 3%. Purified by flash column chromatography, 50%
EtOAc–hexanes.
N-(3-Formylquinolin-7-yl)acetamide (7b)
Yield: 87%. Purified by recrystallization from EtOAc (25 mL) and
hexanes (10 mL); mp 208–210°C.
1H NMR (300 MHz, DMSO-d6): = 10.5 (s, 1 H), 10.1 (s, 1 H), 9.16
(d, 1 H, J = 1.9 Hz), 8.79 (s, 1 H), 8.47 (s, 1 H), 8.10 (d, 1 H, J = 9.0
Hz), 7.75 (dd, 1 H, J = 9.0, 1.9 Hz), 2.10 (s, 3 H).
1H NMR (400 MHz, DMSO-d6): = 11.0 (br s, 1 H), 10.2 (s, 1 H),
9.19 (d, 1 H, J = 2.1 Hz), 9.03 (d, 1 H, J = 2.1 Hz), 7.73 (t, 1 H,
J = 7.9 Hz), 7.52 (d, 1 H, J = 8.3 Hz), 7.02 (d, 1 H, J = 7.5 Hz).
5,7-Dimethoxyquinoline-3-carbaldehyde (7m)
Yield: 83%. Purified by recrystallization from EtOAc (20 mL) and
hexanes (30 mL); mp 197–198 °C.
1H NMR (400 MHz, CDCl3): = 10.2 (br s, 1 H), 9.24 (s, 1 H), 8.95
(d, 1 H, J = 1.7 Hz), 7.15 (s, 1 H), 6.59 (d, 1 H, J = 1.7 Hz), 4.02 (s,
3 H), 3.99 (s, 3 H).
13C NMR (100 MHz, DMSO-d6) 192.7, 170.0, 151.6, 150.2,
143.7, 131.2, 128.0, 123.5, 121.7, 115.9, 25.0.
MS (APCI): m/z = 215.1 (M + H), 213.1 (M – H).
HRMS (FAB): m/z Calcd for C12H10N2O2: (MH)+ 215.0821. Found:
215.0832.
13C NMR (100 MHz, DMSO-d6) = 192.6, 164.7, 157.5, 153.0,
150.5, 134.9, 126.8, 115.5, 100.9, 100.0, 57.1, 56.6.
7-Dimethylaminoquinoline-3-carbaldehyde (7c)
Yield: 96%. Purified by flash column chromatography, 60%
EtOAc–hexanes; mp 95–98°C.
1H NMR (400 MHz, DMSO-d6): = 10.0 (s, 1 H), 9.02 (d, 1 H,
J = 2.1 Hz), 8.59 (d, 1 H, J = 2.1 Hz), 7.93 (d, 1 H, J = 9.1 Hz), 7.34
(dd, 1 H, J = 9.1, 2.5 Hz), 7.00 (d, 1 H, J = 2.5 Hz), 3.11 (s, 6 H).
MS (APCI): m/z = 217.9 (M + H).
Anal. Calcd for C12H11NO3: C, 66.35; H, 5.10; N, 6.45. Found: C,
66.43; H, 5.30; N, 6.54.
6,7-Dimethoxyquinoline-3-carbaldehyde (7n)17
Yield: 78%. Purified by flash column chromatography, 40%
EtOAc–hexanes); mp 160–162 °C.
1H NMR (400 MHz, CDCl3): = 10.2 (br s, 1 H), 9.15 (d, 1 H,
J = 1.2 Hz), 8.48 (d, 1 H, J = 2.1 Hz), 7.50 (s, 1 H), 7.18 (s, 1 H), 4.08
(s, 3 H), 4.05 (s, 3 H).
13C NMR (100 MHz, DMSO-d6): = 191.9, 153.7, 152.7, 150.5,
139.6, 131.5, 125.6, 119.2, 117.6, 105.9, 40.5, 40.4.
MS (APCI): m/z = 201.0 (M + H).
HRMS (FAB): m/z Calcd for C12H12N2O: (MH)+ 201.1028. Found:
201.1022.
13C NMR (100 MHz, CDCl3): = 191.0, 155.3, 150.9, 148.5, 148.1,
137.3, 127.6, 123.1, 108.2, 106.4, 56.7, 56.5.
7-Methylquinoline-3-carbaldehyde (7d)18
MS (APCI): m/z = 218.0 (M + H).
Yield: 71%. Purified by flash column chromatography, 40%
EtOAc–hexanes; mp 114–115°C.
1H NMR (400 MHz, DMSO-d6): = 10.2 (s, 1 H), 9.22 (d, 1 H,
J = 2.1 Hz), 8.89 (d, 1 H, J = 2.1 Hz), 8.09 (d, 1 H, J = 8.3 Hz), 7.90
(s, 1 H), 7.57 (dd, 1 H, J = 8.7, 1.7 Hz), 2.31 (s, 3 H).
[1,3]Dioxolo[4,5-g]quinoline-7-carbaldehyde (7o)
Yield: 75%. Purified by flash column chromatography, 40%
EtOAc–hexanes); mp 155–156 °C.
1H NMR (400 MHz, CDCl3): = 10.2 (s, 1 H), 9.13 (d, 1 H, J = 1.7
Hz), 8.44 (d, 1 H, J = 2.1 Hz), 7.47 (s, 1 H), 7.19 (s, 1 H), 6.19 (s, 2
H).
13C NMR (100 MHz, CDCl3): = 190.9, 153.7, 150.0, 149.2, 148.2,
137.7, 127.6, 124.6, 106.3, 104.1, 102.7.
13C NMR (100 MHz, DMSO-d6): = 192.9, 151.0, 149.6, 144.1,
140.7, 130.7, 130.3, 128.7, 128.6, 125.4, 22.3.
MS (APCI): m/z = 171.9 (M + H), 169.5 (M – H).
7-Phenylquinoline-3-carbaldehyde (7i)
MS (APCI): m/z = 202.0 (M + H).
Yield: 43%. Purified by flash column chromatography, gradient of
20% EtOAc–hexanes to 30% EtOAc–hexanes); mp 118–119°C.
1H NMR (400 MHz, DMSO-d6): = 10.2 (s, 1 H), 9.30 (d, 1 H,
J = 2.1 Hz), 8.98 (d, 1 H, J = 1.7 Hz), 8.36 (s, 1 H), 8.30 (d, 1 H,
J = 8.7 Hz), 8.09 (dd, 1 H, J = 8.7, 2.1 Hz), 7.91 (m, 2 H), 7.55 (m,
2 H), 7.46 (m, 1 H).
Anal. Calcd for C11H7NO3: C, 65.67; H, 3.51; N, 6.96. Found: C,
65.41; H, 3.42; N, 6.92.
5-Amino-7-chloroquinoline-3-carbaldehyde (8p)
Yield: 33%. Purified by flash column chromatography, gradient of
70% EtOAc–hexanes to EtOAc; mp >270 °C.
13C NMR (100 MHz, DMSO): = 192.9, 150.8, 150.1, 144.8, 140.7,
139.4, 131.3 (2 C), 129.9, 129.4, 129.1, 128.1 (2 C), 127.7, 126.7,
121.6.
1H NMR (400 MHz, CDCl3): = 10.1 (s, 1 H), 9.01 (d, 1 H, J = 1.7
Hz), 8.66 (d, 1 H, J = 1.7 Hz), 7.26 (d, 1 H, J = 2.1 Hz), 6.94 (d, 1 H,
J = 2.1 Hz), 6.68 (br s, 2 H).
MS (APCI): m/z = 234.0 (M + H).
13C NMR (100 MHz, DMSO-d6): = 192.0, 153.9, 153.3, 150.8,
136.5, 133.6, 125.7, 119.8, 117.1, 106.2.
Anal. Calcd for C16H11NO: C, 82.38; H, 4.75; N, 6.00. Found: C,
82.33; H, 4.91; N, 6.26.
MS (APCI): m/z = 207.1 (M + H), 205.1 (M – H).
HRMS (FAB): m/z Calcd for C10H7N2OCl: (MH)+ 207.0325.
Found: 207.0320.
7-Hydroxyquinoline-3-carbaldehyde (7k)
Yield: 61%. Purified by recrystallization from EtOAc (5 mL) and
hexanes (5 mL); mp >270°C.
1H NMR (400 MHz, DMSO-d6): = 10.8 (s, 1 H), 10.1 (s, 1 H), 9.11
(d, 1 H, J = 2.1 Hz), 8.76 (d, 1 H, J = 1.7 Hz), 8.03 (d, 1 H, J = 9.1
Hz), 7.29 (d, 1 H, J = 2.1 Hz), 7.25 (dd, 1 H, J = 9.1, 2.5 Hz).
5-Methoxy-7-trifluoromethylquinoline-3-carbaldehyde (8q)
Yield: 16%. Purified by flash column chromatography, gradient of
20% EtOAc–hexanes to 40% EtOAc–hexanes); mp 159–160 °C.
1H NMR (400 MHz, CDCl3): = 10.3 (s, 1 H), 9.41 (d, 1 H, J = 2.1
13C NMR (100 MHz, DMSO-d6): = 192.6, 162.4, 152.7, 150.1,
Hz), 9.07 (d, 1 H, J = 2.1 Hz), 8.05 (s, 1 H), 7.06 (s, 1 H), 4.12 (s, 3
140.5, 132.3, 127.0, 121.6, 121.2, 111.0.
H).
MS (APCI): m/z = 173.8 (M + H), 171.8 (M – H).
Synthesis 2001, No. 9, 1351–1355 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
An Efficient Synthesis of Substituted Quinolines
(9) For a report on recent advances in the synthesis of
1355
13C NMR (100 MHz, CDCl3): = 190.7, 157.3, 150.6, 135.6, 134.1
(d, 1 C, J = 32.5 Hz), 134.1, 129.2, 123.3 (d, 1 C, J = 272.2 Hz),
122.4, 119.3, 101.5, 56.6.
vinamidinium salts, see: Davies, I. W.; Marcoux, J.-F.; Wu,
J.; Palucki, M.; Corley, E. G.; Robbins, M. A.; Tsou, N.;
Ball, R. G.; Dormer, P.; Larsen, R. D.; Reider, P. J. J. Org.
Chem. 2000, 65, 4571.
MS (APCI): m/z = 256.1 (M + H).
(10) Cho, I.-S.; Gong, L.; Muchowski, J. M. J. Org. Chem. 1991,
56, 7288.
(11) Gagan, J. M. F.; Lloyd, D. J. Chem. Soc. C 1970, 2488.
(12) Keshavartz, K. M.; Cox, S. D.; Angus, J. R. O.; Wudl, F.
Synthesis 1988, 641.
(13) Arnold, Z. Collect. Czech. Chem. Commun. 1961, 26, 3051.
(14) Gupton, J. T.; Gall, J. E.; Riesinger, S. W.; Smith, S. Q.;
Bevirt, K. M.; Sikorski, J. A.; Dahl, M. L.; Arnold, Z. J.
Heterocycl. Chem. 1991, 28, 1281.
Acknowledgements
The authors would like to thank Drs. Stephané Caron, Bob Dugger,
Keith DeVries, John Ragan, and Frank Urban for helpful discussi-
ons.
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Synthesis 2001, No. 9, 1351–1355 ISSN 0039-7881 © Thieme Stuttgart · New York