Palladium-catalysed reactions of 8-hydroxy- and 8-benzyloxy-5,7- diiodoquinoline under aminocarbonylation conditions

Article abstract of DOI:10.1016/j.tet.2011.02.003

Various 5-carboxamido-7-iodo-8-benzyloxyquinolines were synthesised via selective aminocarbonylation of 5,7-diiodo-8-benzyloxyquinoline in the presence of 'in situ' generated palladium(0) catalysts. Under similar conditions (50 °C, 80 bar CO), 5,7-bis(N-tert-butyl-glyoxylamido)-8-hydroxyquinoline was obtained using tert-butylamine as N-nucleophile. The unprotected 5,7-diiodo-8-hydroxyquinoline underwent dehydroiodination resulting in 8-hydroxyquinoline as the major product.

Full text of DOI:10.1016/j.tet.2011.02.003

Tetrahedron 67 (2011) 2402e2406
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journal homepage: www.elsevier.com/locate/tet
Palladium-catalysed reactions of 8-hydroxy- and 8-benzyloxy-
5,7-diiodoquinoline under aminocarbonylation conditions
a
a
a
b
c
c,
*
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
Attila Takacs , Antal Szilagyi , Peter Acs , Laszlo Mark , Andreia F. Peixoto , Mariette M. Pereira
,
a
,
*
ꢀ
ꢀ
ꢀ
Laszlo Kollar
a
ꢀ
ꢀ
Department of Inorganic Chemistry, University of Pecs, H-7624 Pecs, P.O. Box 266, Hungary
b
ꢀ
ꢀ
Institute of Biochemistry and Medical Chemistry, University of Pecs, H-7624 Pecs, P.O. Box 266, Hungary
c Departamento de Quimica, Universidade de Coimbra, Rua Larga, 3004-535 Coimbra, Portugal
a r t i c l e i n f o
a b s t r a c t
Article history:
Various 5-carboxamido-7-iodo-8-benzyloxyquinolines were synthesised via selective aminocarbonylation
of 5,7-diiodo-8-benzyloxyquinoline in the presence of ‘in situ’ generated palladium(0) catalysts. Under
similar conditions (50 ꢀC, 80 bar CO), 5,7-bis(N-tert-butyl-glyoxylamido)-8-hydroxyquinoline was ob-
tained using tert-butylamine as N-nucleophile. The unprotected 5,7-diiodo-8-hydroxyquinoline un-
derwent dehydroiodination resulting in 8-hydroxyquinoline as the major product.
Received 22 October 2010
Received in revised form 11 January 2011
Accepted 1 February 2011
Available online 23 February 2011
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Iodo-aromatics
8-Hydroxyquinoline
Aminocarbonylation
Carbon monoxide
Palladium
1. Introduction
ourparent modelcompound, 5,7-diiodoquinoline-8-ol, itwasused as
a ligand for the spectrophotometric determination of yttrium11 and
The introduction of a carboxamide moiety into a skeleton of
practical importance, via simple homogeneous catalytic methods,
is of high interest.1,2 There are a number of applications both for the
synthesis of simple building blocks and for the functionalization of
biologically important skeletons.3,4
The aminocarbonylation of aryl- and enol-triflates leading to
aryl and unsaturated carboxamides, respectively, has been carried
out.5 Recently, iodoarenes and iodoalkenes, the corresponding
synthetic analogues of aryl triflates, have found important appli-
cations as substrates in carbonylation reactions.
erbium12 in a ternary ion-association complex. 3,6-Diiodoquinoline
served as a coupling partner to 1,4-diethynyl-benzene derivative in
palladium-catalysed reaction providing a novel copolymer.13
Accordingly, due to the importance of diiodoquinolines, the facile,
selective, high-yielding palladium-catalysed aminocarbonylation of
5,7-diiodo-8-benzyloxyquinoline with various N-nucleophiles, as
well as the dehydroiodination of its 8-hydroxy analogue are de-
scribed in the present paper.
2. Results and discussion
Palladium-catalysed cross-coupling reactions of iodoquinoline
derivatives with alkynes have been carried out in order to synthesise
tri-substituted pyrroloquinolines6 and 4-substituted quinolines.7
Recently, we published carbonylation reactions of 5-chloro-7-iodo-
quinoline derivatives.8 The improvement of alternative synthetic
methods for alkoxyquinoline derivatives is of great interest due to
their potential biological activity as PDE4 inhibitors9 as well as for the
preparation of electroluminescent materials for organic LEDs.10 As for
2.1. Aminocarbonylation of 5,7-diiodo-8-benzyloxyquinoline (1)
5,7-Diiodo-8-benzyloxyquinoline (1), prepared from 5,7-iodo-8-
hydroxyquinoline (4) with benzyl bromide,14 was reacted with
various amines and carbon monoxide in the presence of ‘in situ’
palladium(0) catalysts (Scheme 1). The formation of highly active,
low-ligated palladium(0) complexes from the palladium(II) pre-
cursors, such as Pd(OAc)2 used in our systems, was proved by cyclic
voltammetry and NMR measurements.15,16 The aminocarbonylation
under high pressure (80 bar) was unexpectedly regioselective at
position-5 resulting in 2a and 2b by using secondary amines, such as
morpholine (a) and piperidine (b), respectively (Table 1, entries 1
* Corresponding authors. E-mail addresses: mmpereira@qui.uc.pt (M.M. Pereira),
ꢀ
kollar@ttk.pte.hu (L. Kollar).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.02.003

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A. Takacs et al. / Tetrahedron 67 (2011) 2402e2406
2403
and 2). Carrying out the reaction under the same carbon monoxide
pressure even 5-(N-phenylcarboxamide) derivative (2c) could be
isolated by using aniline (entry 3). Arylamines of low basicity have
shown low reactivity in aminocarbonylation of both iodoarene and
iodoalkene type substrates.17,18 When the reaction was carried out
by using one of the most reactive primary amines, tert-butylamine
(d), much lower carbon monoxide pressure proved to be sufficient to
yield the same type of carboxamide, 2d (entry 4).
was isolated as minor product (8%). It is worth noting that the ami-
nocarbonylationof simpleiodoarenes, suchasiodobenzeneor 2-iodo-
naphthalene provided a mixture of the corresponding carboxamides
and 2-ketocarboxamides with the prevailing formation of the latter
product under similar reaction conditions.19
However, the use of tert-butylamine (d) for aminocarbonylation
under high carbon monoxide pressure resulted in the formation of
5,7-bis(tert-butyl-glyoxylamido)-8-hydroxyquinoline (3) as a ma-
jor product (entry 6). The expected 5,7-bis(tert-butyl-glyox-
ylamido)-8-benzyloxyquinoline (30) was formed as a minor product
only (<6%) and was detected by NMR spectroscopy as a minor
component of a mixture formed with 3. The most interesting fea-
ture of the latter reaction is the almost complete deprotection of
the 8-benzyloxy functionality while double carbonylation occurred
at both iodoarene functionalities.
O
NHtBu
tBuHN
tBuHN
O
NR'R"
N
N
I
O
OBn
2d'
CO, HNR'R"
Pd(OAc)2 / PPh3
I
I
N
NHtBu
2.2. Palladium-catalysed dehydroiodination of 5,7-diiodo-8-
hydroxyquinoline
OBn
1
OBn
2a-d
O
O
R'
R''
5,7-Diiodo-8-hydroxyquinoline (4) was subjected to amino-
carbonylation as its 8-protected derivative, 1 under similar reaction
conditions (60 bar CO, 50 ꢀC) (Scheme 2). Unexpectedly, no car-
boxamide or ketocarboxamide derivatives were formed. 8-
Hydroxyquinoline (6), the ‘fully dehydroiodinated’ derivative of 4,
was formed as the major or exclusive product in all cases (vide
infra).
a
-(CH2)2O(CH2)2-
-(CH2)5-
N
O
b
c
d
OBn
2d''
H
Ph
H
tBu
NHtBu
O
I
O
I
CO (80 bar), H2NtBu
O
Pd(OAc)2 / PPh3
I
N
tBuHN
N
I
O
I
OBn
N
OH
N
CO, HNR'R"
OH
5'
OH
5
1
3
Pd(OAc)2 / PPh3
I
N
Scheme 1. Aminocarbonylation of 5,7-diiodo-8-benzyloxyquinoline (1).
OH
4
N
OH
6
Table 1
Aminocarbonylation of 5,7-diiodo-8-benzyloxyquinoline (1) with various aminesa
R'
R''
Entry Amine Amine/
R. time [h] p(CO) [bar] Product
a
-(CH2)2O(CH2)2-
-(CH2)5-
substrate ratio
(isolated yield)b [%]
b
c
d
1
2
3
4
5
6
a
b
c
d
d
d
3/1 2a (87)
25
25
70
70
58
70
80
80
80
1
20
80
H
H
H
Ph
tBu
CH2COOCH3
3/1
4/1
6/1
6/1
6/1
2b (86)
2c (81)
2d (76)
e
2d0 (40); 2d00 (8)
3 (47)
Scheme 2. Dehydroiodination of 5,7-diiodo-8-hydroxyquinoline (4) under carbonyl-
ation conditions.
a
Reaction conditions: 0.025 mmol Pd(OAc)2; 0.05 mmol PPh3; 1 mmol substrate;
10 mL DMF; 0.5 mL Et3N; 50 ꢀC; practically full conversions (>98%) were obtained in
The application of high-pressure conditions led to the exclusive
formation of 6 by using both secondary (a and b) and primary (c and
d) amines (Table 2, entries 1,2 and entries 4,5, respectively). The only
exceptionamongthe used aminesis methylglycinate (e)(entry 9). In
this peculiar case the monoiodo-8-hydroxyquinoline isomers (5 and
50), due to monodehydroiodination, were also formed. The latter
products were obtained as major ones at a ratio of 60/40 when at-
mosphericcarbon monoxide pressureand d wereused(entry 8). The
syntheses of the iodo-8-hydroxyquinolines (5 and 50) were pub-
lished before.20,21 It has to be added that the above reaction is always
accompanied by the direct carbonylation of the amine resulting in
the corresponding urea-type compound ((R0R00N)2CO) (see also
Scheme 3) or in the oxalylamide-type compounds ((R0R00N)2(CO)2),
the latter one detected in traces only by GC/MS.
It has to be added that an oxidative addition followed by
dehydroiodination might be operative. The following simplified
reaction mechanism, including the involvement of the phenolic OH
group, is suggested for dehydroiodination. A plausible mechanism
for the dehydroiodination process is depicted in Scheme 3. The
oxidative addition of the substrate (4) on low-ligated Pd(0) species,
all cases.
b
Isolated yields are based on the amount of the starting material (1).
It is worth noting that the aminocarbonylation proceeds with
high regioselectivity leading to 5-carboxamido derivatives, i.e., the
7-iodoaryl functionality remained untouched. The characterization
of the products was carried out by detailed NMR measurements
including 2D NMR techniques (HMBC, HSQC). Even the practically
unchanged chemical shift of the sharp singlet in 1H NMR, assigned
to the methylene protons (at ca. 5.5 ppm), suggests that carbonyl-
ation occurred in position-5 in case of the monocarbonylated
products 2aed. When carbonylation took place in position-7 as
well (2d0 and 2d00) the above signal has a downfield shift of 0.1 and
0.2 ppm, respectively.
Theexpected5,7-dicarboxamidecanbeobtainedwith40%isolated
yield only with tert-butylamine (d) as N-nucleophile under optimized
reaction conditions (58 h, 20 bar CO) (entry 5). Under these reaction
conditions the corresponding carboxamideeketocarboxamide de-
rivative (2d00) resulting from double carbonyl insertion in position-5

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A. Takacs et al. / Tetrahedron 67 (2011) 2402e2406
2404
Table 2
Dehydroiodination of 5,7-diiodo-8-hydroxyquinoline (4) with various amines under aminocarbonylation conditionsa
b
Entry
Amine
Amine/substrate ratio
R. time [h]
p(CO) [bar]
Product distribution [%]
Isolated yieldc [%]
1
2
3
4
5
6
7
8
9
a
3/1
3/1
3/1
4/1
6/1
6/1
6/1
6/1
3/1
24
24
20
70
70
48
24
70
24
70
70
1
70
80
40
10
1
6 (100)
6 (81)
6 (83)
n.d.e
b
b
c
d
d
d
d
ed
6 (100)
5 (39); 50 (61)f
6 (100)
6 (77)
6 (74)
n.d.e
6 (100)
6 (100)
6 (100)
n.d.e
5 (60); 50 (40)
6 (60); 5 (30); 50 (10)
5 (45)
6 (51)
70
a
Reaction conditions: 0.025 mmol Pd(OAc)2; 0.05 mmol PPh3; 1 mmol substrate; 10 mL DMF; 0.5 mL Et3N; 50 ꢀC; practically full conversions (>98%) were obtained (unless
otherwise stated).
b
Determined by GC/MS.
Isolated yields are based on the amount of the starting material (4).
Compound e was used as hydrochloride salt.
Not determined.
c
d
e
f
Conversion 32%.
Furthermore, the control of CO pressure allowed the formation of the
bis-carboxamide or the carboxamideeketocarboxamide derivative
using the most reactive tert-butylamine. Unexpectedly, either com-
plete or partial dehydroiodination of 5,7-diiodo-8-hydroxyquinoline
took place leading to 8-hydroxyquinoline or iodo-8-hydroxyquino-
line isomers, respectively, in the presence of most primary and sec-
ondary amines under homogeneous carbonylation conditions.
4. Experimental
4.1. General procedures
1H and 13C NMR spectra were recorded in CDCl3 on a Varian
Inova 400 spectrometer at 400.13 MHz and 100.62 MHz, re-
spectively. Chemical shifts
d are reported in parts per million rela-
tive to CHCl3 (7.26 and 77.00 ppm for 1H and 13C, respectively).
Elemental analyses were measured on a 1108 Carlo Erba apparatus.
Samples of the dehydrogenation reactions were analysed with
a Hewlett Packard 5830A gas chromatograph fitted with a capillary
column coated with OV-1. The MALDI-TOF spectra of the isolated
carboxamides were obtained on an Autoflex II TOF/TOF spectrom-
eter (Bruker Daltonics) in positive ion modes, using 2,5-dihydrox-
ybenzoic acid (DHB) as matrix.
5,7-Diiodo-8-benzyloxyquinoline was synthesised according to
the benzylation of 5,7-dibromo-8-hydroxyquinoline as described
previously.14 5,7-iodo-8-hydroxyquinoline, as well as the amines
were purchased from Aldrich and were used without any further
purification. Solvents were dried and purified by generally used
Scheme 3. A proposed mechanism for dehydroiodination of 4.
formed in situ from the Pd(II) precursor, resulted in the iodo-aryl-
palladium(II) species (A). Its dehydroiodination by triethylamine
leads to B, which activates the primary or secondary amine by
forming the aryleamido complex (C). The coordination of carbon
monoxide as a terminal carbonyl (not indicated on the Scheme) and
its insertion into the PdeN bond resulted in the formation of the
corresponding carbamoyl-palladium(II) complex (D). The carba-
moyl species reacts with the ‘second’ primary or secondary amine
forming the urea-type product (carbonylation of the amine) and
the aryl-hydrido-species (E). The reductive elimination provides
the dehydroiodination product and the palladium(0) species in the
product-forming step. Consequently, the hydrogen necessary to
formal dehydroiodination stems from the amine.
procedures.
21
The syntheses of the dehydroiodination products (520 and 50
)
were published and the analytical data are in good agreement with
those obtained in the present study. The missing analytical data of
these known compounds are also presented below.
4.2. Aminocarbonylation reaction at high-pressure
In a typical reaction 5.6 mg (0.025 mmol) of Pd(OAc)2 and
13.1 mg (0.05 mmol) of PPh3 together with 1 mmol of substrate (1)
were placed into a 100 mL autoclave equipped with a magnetic
stirring bar. The atmosphere was changed to argon and all the solid
substances were dissolved in 10 mL of DMF, then 0.5 mL of trie-
thylamine and 0.6 mL (6 mmol) tert-butylamine (d) (or 3 mmol of a,
b; 4 mmol of c) were added. The atmosphere was changed to carbon
monoxide, the autoclave was pressurized bycarbon monoxide tothe
given pressure and the reaction mixture was kept at 50 ꢀC for
the given reaction time. The solvent was evaporated to dryness and
the residue dissolved in chloroform. It was washed three times with
3. Conclusions
5-Carboxamido-7-iodo-8-benzyloxyquinolines were synthesised
in high-yielding palladium-catalysed aminocarbonylation of 5,7-
diiodo-8-benzyloxyquinoline. The iodoarene functionality of the
target carboxamides is suitable for further functionalization.

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A. Takacs et al. / Tetrahedron 67 (2011) 2402e2406
2405
water and brine. The organic phase was dried over Na2SO4 and
evaporated. The carboxamides were isolated via column chroma-
tography by using chloroform/ethyl acetate mixtures as eluents (for
exact ratios see analytical characterization below).
IR (KBr, (cmꢁ1)): 3375 (NH); 1639 and 1659 (CON). FABMS:
434.2445 (MþH) (calcd 434.2444). Anal. Calcd for C26H31N3O3
(433.55): C, 72.03; H, 7.21; N, 9.69; found: C, 71.77; H, 7.40; N, 9.45;
Rf (15% EtOAc/CH2Cl2) 0.68; mp 59e61 ꢀC. Pale yellow solid. Yield:
172 mg (40%).
4.3. Analytical and spectroscopic data of compounds
4.3.6. 7-(N-tert-Butylcarboxamido)-5-(N-tert-butylglyoxylamido)-8-
4.3.1. 5-(N,N-(Penta-30-oxa-10,50-diyl)carboxamido)-7-iodo-8-benzy-
benzyloxyquinoline (2d00). 1H NMR (CDCl3)
d
: 8.97 (d, J¼2.0 Hz, 1H,
loxyquinoline (2a). 1H NMR (CDCl3)
d: 8.96 (d, J¼3.7 Hz, 1H, H-2);
H-2); 8.80 (d, J¼8.0 Hz, 1H, H-4); 7.69 (s, 1H, H-6); 7.50 (d,
J¼7.1 Hz, 2H, Ph), 7.54 (dd, J¼5.0 and 3.4 Hz, 1H, H-3); 7.31e7.38
(m, 3H, Ph); 6.01 (br s, 1H, NH); 6.42 (br s, 1H, NH); 5.75 (s, 2H,
OCH2); 1.51 (s, 9H, C(CH3)3); 1.34 (s, 9H, C(CH3)3). 13C NMR
8.20 (d, J¼8.3 Hz, 1H, H-4); 7.82 (s, 1H, H-6); 7.67 (d, J¼7.3 Hz, 2H,
Ph); 7.31e7.55 (m, 4H, PhþH-3); 5.51 (s, 2H, OCH2); 3.75e3.99 (m,
4H, O(CH2)2); 3.43e3.70 (m, 2H, NCH2); 3.19e3.35 (m, 2H, NCH2).
13C NMR (CDCl3)
d: 166.9; 157.1; 150.5; 142.6; 137.2; 134.2; 133.8;
(CDCl3) d: 193.0; 167.0; 161.4; 157.2; 149.8; 142.3; 137.5; 134.8;
132.3; 129.1 (double intensity); 128.5 (double intensity); 128.4;
127.1; 122.6; 91.2; 76.8; 67.2 (double intensity); 48.1; 42.7. IR (KBr,
(cmꢁ1)): 1628 (CON). MS m/z: 474 (Mþ), 347 (MþꢁI). Anal. Calcd for
C21H19N2O3I (474.30): C, 53.18; H, 4.04; N, 5.91; found: C, 53.41; H,
4.29; N, 5.64; Rf (50% EtOAc/CHCl3) 0.41; mp 120e121 ꢀC. Yellow
solid. Yield: 410 mg (87%).
130.8; 130.0; 128.3 and 128.2 (double intensity); 128.0; 126.5;
124.7; 123.3; 77.6; 52.3; 51.7; 28.8; 28.3. IR (KBr, (cmꢁ1)): 3278
(NH); 1658 and 1640 (CON). FABMS: 462.2398 (MþH) (calcd
462.2393); Rf (15% EtOAc/CH2Cl2) 0.50; mp 64e66 ꢀC. Green solid.
Yield: 37 mg (8%).
4.3.7. 5,7-Bis(N-tert-butyl-glyoxylamido)-8-hydroxyquinoline
4.3.2. 5-(N,N-(Penta-10,50-diyl)carboxamido)-7-iodo-8-benzylox-
(3). 1H NMR (CDCl3)
d
: 9.42 (s, 1H, H-6); 9.22 (d, J¼2.8 Hz, 1H, H-2);
yquinoline (2b). 1H NMR (CDCl3)
d
: 8.96 (d, J¼3.8 Hz, 1H, H-2); 8.19
8.69 (br s, 1H, H-4); 8.20 (br s, 1H, OH); 7.58 (dd,1H, H-3); 6.71 (br s,
(d, J¼8.0 Hz, 1H, H-4); 7.80 (s, 1H, H-6); 7.66 (d, J¼7.3 Hz, 2H, Ph);
7.51 (dd, J¼3.8, 8.0 Hz, 1H, H-3); 7.31e7.40 (m, 3H, Ph); 5.49 (s, 2H,
OCH2); 3.75e3.90 (m, 2H, (NCH2)2); 3.17 (br s, 2H, NCH2); 1.35e1.80
1H, NH); 6.66 (br s, 1H, NH); 1.50 (s, 18H, 2ꢂC(CH3)3). 13C NMR
(CDCl3) d: 189.8; 189.7; 163.7; 163.4; 155.3; 148.0; 142.3; 138.6;
135.0; 130.1; 126.3; 115.1; 107.9; 52.1; 52.0; 28.7. IR (KBr, (cmꢁ1)):
3307 (NH); 1677 (CON); 1628 (CON). MS m/z: 421 (MþꢁHþNa), 299
(MþꢁCONHtBu). Anal. Calcd for C21H25N3O5 (399.45): C, 63.15; H,
6.31; N, 10.52; found: C, 63.31; H, 6.42; N, 10.30; Rf (20% EtOAc/
CHCl3) 0.44; mp 104e105 ꢀC. Yellow solid. Yield: 188 mg (47%).
(m, 6H, (CH2)3). 13C NMR (CDCl3)
d: 166.7; 156.3; 150.4; 142.6;
137.3; 134.1; 133.6; 131.9; 129.0 (double intensity); 128.5 (double
intensity); 128.3; 127.1; 122.4; 91.4; 76.8; 48.8; 43.2; 27.0; 26.0;
24.7. IR (KBr, (cmꢁ1)): 1630 (CON). MS m/z: 472 (Mþ), 345 (MþꢁI).
Anal. Calcd for C22H21N2O2I (472.33): C, 55.94; H, 4.48; N, 5.93;
found: C, 55.71; H, 4.59; N, 5.66; Rf (40% EtOAc/CHCl3) 0.69. Highly
viscous yellow oil. Yield: 405 mg (86%).
4.3.8. 5-Iodo-8-hydroxy-quinoline (5). 1H NMR (CDCl3)
d: 8.75 (d,
J¼2.4 Hz, 1H, H-2); 8.10 (d, J¼8.2 Hz, 1H, H-4); 7.75 (d, J¼8.4 Hz, 1H,
H-7); 7.45 (dd, J¼4, 8.4 Hz,1H, H-3); 7.09 (d, J¼8.4 Hz,1H, H-6), 6.95
4.3.3. 5-(N-Phenylcarboxamido)-7-iodo-8-benzyloxyquinoline
(br s, 1H, OH). 13C NMR (CDCl3)
d: 153.2, 148.7, 137.7, 136.5, 136.4,
(2c). 1H NMR (CDCl3)
d
: 8.96 (d, J¼3.4 Hz, 1H, H-2); 8.75 (d,
128.3, 122.5, 119.4, 90.8. MS m/z: 271/100 (Mþ), 243/7, 144/6, 116/
33. Anal. Calcd for C9H6ION (271.06): C, 39.88; H, 2.23; N, 5.17;
found: C, 39.75; H, 2.47; N, 4.88. Highly viscous yellow oil. Yield:
122 mg (45%).
J¼8.2 Hz, 1H, H-4); 8.08 (s, 1H, H-6); 7.90 (br s, 1H, NH); 7.60e7.68
(m, 4H, Ph); 7.49 (dd, J¼3.4, 8.2 Hz, 1H, H-3); 7.28e7.40 (m, 6H, Ph);
5.54 (s, 2H, OCH2). 13C NMR (CDCl3)
d: 164.9; 157.8; 150.4; 142.6;
137.9; 137.1; 135.1; 134.9; 131.2; 129.4 (double intensity); 129.0
(double intensity); 128.5 (double intensity); 128.4; 127.8; 125.2;
122.8; 121.1; 120.4; 90.4; 76.9. IR (KBr, (cmꢁ1)): 3270 (NH); 1644
(CON). MS m/z: 480 (Mþ), 353 (MþꢁI). Anal. Calcd for C23H17N2O2I
(480.30): C, 57.52; H, 3.57; N, 5.83; found: C, 57.40; H, 3.69; N, 5.70;
Rf (10% EtOAc/CHCl3) 0.55; mp 178e179 ꢀC. Pale yellow solid. Yield:
390 mg (81%).
4.3.9. 7-Iodo-8-hydroxyquinoline (50). Compound 50 (isolated as
a 70/30 mixture of 5/50): MS m/z: 271/100 (Mþ), 243/10,144/5,116/30.
Acknowledgements
The authors thank the Hungarian Research Fund (OTKA
CK78553), the Joint Project of the European UniondHungarian
National Development Program (GVOP-3.2.1-2004-04-0168/3) and
Science, Please! Research Team on Innovation (SROP-4.2.2./08/1/
2008-0011) and Portuguese Foundation FCT (PTDC/QUI-QUI/
112913/2009) for the financial support and Johnson Matthey for the
generous gift of palladium(II) acetate. A.F. Peixoto also thanks FCT
for the Ph.D. grant SFRH/BD/29681/2006.
4.3.4. 5-(N-tert-Butylcarboxamido)-7-iodo-8-benzyloxyquinoline
(2d). 1H NMR (CDCl3)
d
: 8.95 (d, J¼3.9 Hz, 1H, H-2); 8.69 (d,
J¼8.4 Hz, 1H, H-4); 7.94 (s, 1H, H-6); 7.66 (d, J¼7.3 Hz, 2H, Ph); 7.51
(dd, J¼3.9, 8.4 Hz, 1H, H-3); 7.32e7.40 (m, 3H, Ph); 5.80 (br s, 1H,
NH); 5.53 (s, 2H, OCH2); 1.52 (s, 9H, C(CH3)3). 13C NMR (CDCl3)
d:
166.5; 157.1; 150.2; 142.6; 137.2; 134.9; 134.4; 132.7; 129.0 (double
intensity); 128.5 (double intensity); 128.4; 127.7; 122.5; 90.5; 76.7;
52.6; 29.1. IR (KBr, (cmꢁ1)): 3307 (NH); 1634 (CON). MS m/z: 460
(Mþ), 333 (MþꢁI). Anal. Calcd for C21H21N2O2I (460.31): C, 54.80; H,
4.60; N, 6.09; found: C, 54.61; H, 4.69; N, 5.84; Rf (10% EtOAc/CHCl3)
0.59; mp 125e126 ꢀC. Dark green crystals. Yield: 350 mg (76%).
References and notes
€
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1. Skoda-Foldes, R.; Kollar, L. Curr. Org. Chem. 2002, 6, 1097e1119.
2. Arcadi, A. Carbonylation of Enolizable Ketones (Enol Triflates) and Iodoalkenes
ꢀ
(Chapter 9) In Modern Carbonylation Methods; Kollar, L., Ed.; Wiley-VCH:
4.3.5. 5,7-Bis(N-tert-butylcarboxamido)-8-benzyloxyquinoline
Weinheim, 2008; pp. 223e250.
3. Applied Homogeneous Catalysis with Organometallic Compounds; Cornils, B.,
Herrmann, W. A., Eds.; Wiley-VCH: Weinheim, 1996.
4. Transition Metals for Organic Synthesis; Beller, M., Bolm, C., Eds.; Wiley-VCH:
Weinheim, 1998; Vols. IeII.
5. Colquhoun, H. M.; Thompson, D. J.; Twigg, M. V. Carbonylation. Direct Synthesis
of Carbonyl Compounds; Plenum: New York, NY and London, 1991.
6. Kang, S. K.; Park, S. S.; Kim, S. S.; Choi, J.-K.; Yum, E. K. Tetrahedron Lett. 1999, 40,
4379e4382.
(2d0). 1H NMR (CDCl3)
d
: 9.02 (d, J¼4.0 Hz, 1H, H-2); 8.91 (d,
J¼8.0 Hz, 1H, H-4); 8.40 (s, 1H, H-6); 8.19 (br s, 1H, NH); 7.52 (d,
J¼5.8 Hz, 2H, Ph), 7.52e7.56 (m, 1H, H-3); 7.39e7.41 (m, 3H, Ph);
6.06 (br s, 1H, NH); 5.61 (s, 2H, OCH2); 1.52 (s, 9H, C(CH3)3); 1.23 (s,
9H, C(CH3)3). 13C NMR (CDCl3)
d: 167.2; 163.4; 155.3; 149.9; 142.7;
136.3; 135.0; 130.5; 129.3; 129.2 (double intensity); 129.0; 128.8
(double intensity); 126.1; 124.3; 123.0; 79.0; 52.2; 51.3; 28.8; 28.4.
7. Comins, D. L.; Nolan, J. M.; Bori, I. D. Tetrahedron Lett. 2005, 46, 6697e6699.

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11. Vijayalekshmy, B.; Biju, V. M.; Rao, T. P. Indian J. Chem. Technol. 2003, 10,
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