Expeditious functionalization of quinolines in positions 2 and 8 via polyfunctional aryl- and heteroarylmagnesium intermediates

Article abstract of DOI:10.1055/s-2003-36828

An efficient way to prepare functionalized 8-iodo-2-trifluoromethanesulfonyloxyquinolines is presented. The iodo functionality could be selectively converted into other residues via an iodine-magnesium exchange reaction. In addition, the trifluoromethanes

Full text of DOI:10.1055/s-2003-36828

PAPER
233
Expeditious Functionalization of Quinolines in Positions 2 and 8 via
Polyfunctional Aryl- and Heteroarylmagnesium Intermediates
Functionalization
o
n
f
Q
uinolinesne Staubitz, Wolfgang Dohle, Paul Knochel*
Department für Chemie und Pharmazie, Ludwig-Maximilians-Universität München, Butenandtstr. 5–13, Haus F, 81377 München,
Germany
E-mail: Paul.Knochel@cup.uni-muenchen.de
Received 14 November 2002
The conversion of 5a,b, which were prepared according to
literature procedures,4 into the functionalized magnesium
reagents is readily achieved by reaction with i-PrMgCl
(–30 °C, 15–30 min), whereby only the monomagnesium
Abstract: An efficient way to prepare functionalized 8-iodo-2-
trifluoromethanesulfonyloxyquinolines is presented. The iodo func-
tionality could be selectively converted into other residues via an io-
dine–magnesium exchange reaction. In addition, the
trifluoromethanesulfonate functionality was used as a leaving group reagent was formed.5 After a transmetalation with the
THF soluble copper salt CuCN 2LiCl,6 the resulting func-
in Negishi cross-coupling reactions.
tionalized arylcopper species undergoes an addition-elim-
ination reaction with ethyl (Z)-3-iodobut-2-enoate,7
providing the unsaturated esters 6a,b in 81–82% yield.8,9
These esters undergo a cyclization reaction to the hetero-
cycles 7a,b when heated in ethanol with ZnCl2 at reflux
Key words: functionalized organomagnesium reagents, iodine–
magnesium exchange, functionalized heterocycles, cross-coupling,
palladium catalysis
The preparation of functionalized heterocycles is an im- for 12 hours (Scheme 2).
portant synthetic goal since many of these molecules have
unique biological and pharmaceutical properties.1 Recent-
1) i-PrMgCl (1.1 equiv),
THF, –30 °C, 15 – 30 min
FG
I
ly, we have shown that a range of polyfunctional aryl- and
heteroarylmagnesium compounds can be readily prepared
via an iodine– or bromine–magnesium exchange reac-
tion.2 Herein, we wish to report an efficient functionaliza-
tion of iodoquinoline triflates of type 1 via the reactive
quinolylmagnesium intermediates of type 2 obtained via
an iodine–magnesium exchange reaction.3 The successive
reaction of the organometallics 2a,b with an electrophile
(E+) and then with a nucleophile (Nu–) provides a range of
new quinolines of type 3 and 4 selectively functionalized
in positions 8 and 2 (Scheme 1).
2) CuCN·2LiCl (1.1 equiv)
–30 °C, 45 min
N
3)
Me
I
NMe2
5a: FG = CO2Et
5b: FG = CF3
I
CO2Et
–30 °C to 25 °C, 45 min – 3.5 h
Me
Me
FG
FG
ZnCl2 (5 equiv)
CO2Et
EtOH, 80 °C, 12 h
N
N
O
H
I
I
Me
NMe2
Me
FG
FG
i-PrMgCl
6a: FG = CO2Et; 81%
6b: FG = CF3; 82%
7a: FG = CO2Et; 68%
7b: FG = CF3; 92%
THF, –30 °C
N
OTf
N
OTf
Scheme 2 Preparation of the starting heterocyles 7a,b
I
MgCl
1a: FG = CO2Et
1b: FG = CF3
2a: FG = CO2Et
2b: FG = CF3
Preliminary results indicate that 7a can be converted into
the corresponding dimagnesium species 8 by successive
treatment with PhMgCl (1.1 equiv) and i-PrMgCl (1.1
equiv) in THF at –30 °C. PhMgCl was chosen for the
deprotonation of the amide functionalitiy of 7a. This re-
agent is not reactive enough to perform the iodine–mag-
nesium exchange, which is carried out by the subsequent
addition of i-PrMgCl (1.1 equiv). The resulting dimagne-
sium compound 8 reacts with benzaldehyde, affording the
expected benzhydryl alcohol 9 in 58% yield (Scheme 3).
Me
N
FG
1) E
2) Nu
(Pd catalysis)
Nu
4a–f: (81–96 %)
E
3a–i: (41–78 %)
Scheme
1
Preparation of polyfunctional quinolines via the
functionalized quinolylmagnesium species 2a,b
In order to avoid the preparation of a bimetallic species
and to allow further functionalization in position 2, we
have prepared the iodoquinolinyl triflates 1a,b by reacting
7a,b with triflic anhydride (1.2 equiv) and pyridine (3
equiv) in CH2Cl2 (0 to 25 °C, 12 h). The reactions of 1a,b
Synthesis 2003, No. 2, Print: 31 01 03.
Art Id.1437-210X,E;2003,0,02,0233,0242,ftx,en;T11802SS.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0039-7881

234
A. Staubitz et al.
PAPER
(Table 1, entry 1). The bromination of 2a with (CCl2Br)2
leads to the 8-bromoquinoline derivative 3b in 78% yield
(entry 2). After transmetalation with CuCN 2LiCl,6 allyl-
ation with allyl bromide proceed smoothly affording the
functionalized quinolines 3c and 3d in 77% and 70%
yield, respectively (entries 3 and 4). The addition of t-bu-
tyl propiolate leads to the E-unsaturated ester 3e in 41%
yield (entry 5), whereas the addition of propargyl bromide
to 2a leads to the SN2 substitution product 3f accompanied
by small amounts of the isomeric allene in 70% overall
yield (entry 6). Palladium(0)-catalyzed cross-coupling re-
actions of the zinc reagents corresponding to 2a,b
(Negishi cross-coupling)10 with various aromatic and het-
erocyclic iodides furnishes the expected cross-coupling
products 3g–i in 48–74% yield (entries 7–9) (Scheme 5).
Me
EtO2C
1) PhMgCl (1.1 equiv)
2) i-PrMgCl (1.1 equiv)
THF, –30 °C
N
H
O
I
7a
Me
Me
N
EtO2C
EtO2C
PhCHO (3 equiv)
–30 °C, 2 h
N
H
O
O
OH
MgCl MgCl
9: 58%
8
Scheme 3 Generation and reaction of dimagnesium intermediate 8
with i-PrMgCl (1.1 equiv) in THF at –30 °C for 15–40
minutes lead in almost quantitative yield to the desired
Grignard reagents 2a,b (Scheme 4).
Scheme 5 Reaction of the Grignard reagents 2a,b with electrophiles
after transmetalation reactions
The products 3a–i bear a triflate group in position 2 which
can participate in a further Negishi cross-coupling reac-
tion. Thus, the three triflates 3c, 3d and 3h react with var-
ious organozinc reagents in the presence of Pd(dba)2 (3
mol%), tris-o-furylphosphine (tfp, 6 mol%) at 25 °C in
1.5–4 hours, leading to the expected polyfunctional quin-
oline derivatives 4a–f in 81–96% yield (Table 2 and
Scheme 1).
Scheme 4 Preparation of the polyfunctional quinolylmagnesium
compounds 2a,b
Thus, the ester-substituted Grignard reagent 2a reacts di-
rectly with aldehydes such as anisaldehyde, furnishing in
this case the corresponding alcohol 3a in 52% yield
Table 1 Products of Type 3 Obtained by the Reaction of 2a,b with Electrophiles Directly or after Transmetalation with CuCN 2LiCl,6 ZnCl2,
or ZnBr2
Entry
1
Grignard Reagent
Electrophile
Product of Type 3
Yield (%)a
52
2a
p-MeOC6H4CHO
Me
EtO2C
N
OTf
OH
3a
MeO
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Functionalization of Quinolines in Positions 2 and 8
235
Table 1 Products of Type 3 Obtained by the Reaction of 2a,b with Electrophiles Directly or after Transmetalation with CuCN 2LiCl,6 ZnCl2,
or ZnBr2 (continued)
Entry
Grignard Reagent
Electrophile
(CCl2Br)2
Product of Type 3
Yield (%)a
Me
EtO2C
2
2a
78
N
OTf
Br
3b
3
4
2a
2b
allyl bromide
allyl bromide
77b
70b
3d: R = CF3
Me
N
EtO2C
5
6
2a
2a
41b
CO2t-Bu
OTf
3e
CO2t-Bu
Me
EtO2C
70b,c
N
OTf
Br
3f
Me
R
N
OTf
7
2a
74d
I
I
CO2Et
3g: R = CO2Et
CO2Et
8
9
2a
2b
63d
CO2Et
3h: R = CF3
Me
EtO2C
N
N
48d
N
OTf
I
N
N
3i
a Isolated yields of analytically pure products.
b The Grignard reagent was treated with CuCN 2LiCl (1.1 equiv) prior to the addition of the electrophile.
c This product contains approximately 10% of the corresponding allene (see experimental section).
d The Grignard reagent was treated with ZnCl2 (1.0 equiv) prior to the addition of the electrophile.
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A. Staubitz et al.
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Table 2 Polyfunctional Quinolines 4a–f Obtained by Pd(0)-Catalyzed Cross-Coupling of Quinolinyl Triflates with Various Organozinc Re-
agents
Entry
Quinolyl Triflate
Organozinc Reagent
Product of Type 4
Yield (%)a
Me
Me
EtO2C
EtO2C
1
82
Et2Zn
N
Et
N
OTf
4a
Me
3c
EtO2C
2
3
4
5
3c
96
81
92
89
MeO
ZnBr
N
OMe
4b
Me
EtO2C
EtO2C
F3C
F3C
ZnBr
CF3
3c
3c
3d
N
4c
Me
EtO2C
ZnBr
N
CO2Et
4d
Me
EtO2C
ZnBr
N
CO2Et
4e
Me
F3C
N
Et
6
3h
84
Et2Zn
4f
CO2Et
a Isolated yields of analytically pure products.
In summary, we have shown that functionalized amino-
substituted arylmagnesium reagents can be efficiently
used to prepare 8-iodo-2-trifluoromethanesulfonyloxy-
quinolines which can be selectively functionalized in po-
sured on a Bruker ARX 300 spectrometer in CDCl3 or pyridine-d5
and referenced to the solvent signal. Low resolution mass spectra
were recorded on a HP 6890/MSD 5973 spectrometer fitted with a
HP-5 column (30 m × 0.25 mm × 0.25 µm). High resolution mass
sition
2
and
8
by the use of intermediate spectra were run on a Varian MAT 711 spectrometer at an ionizing
potential of 70 eV. Microanalyses were performed using a Heraeus
quinolylmagnesium species.
CHN-Rapid-Elementaranalysator. Flash chromatography was ac-
complished using Merck Kieselgel 60 (230–400 mesh ASTM).
Melting points were measured on a Büchi B 540 apparatus and are
uncorrected. IR spectra were recorded on a FT-IR Perkin-Elmer
1000 spectrophotometer. 1H NMR and 13C NMR spectra were mea-
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Functionalization of Quinolines in Positions 2 and 8
237
Commercially available compounds were used without further pur-
ification. All reactions were carried out in anhydrous solvents under
argon. All organometallic compounds and salts were used as solu-
tions in THF, if not stated otherwise.
(0.94 M, 0.82 mL, 0.77 mmol). After the exchange was complete
(15 min, determined by GC), anisaldehyde (143 mg, 1.05 mmol)
was then added and the reaction mixture was stirred for 1.5 h, after
which time TLC analysis indicated complete conversion. The reac-
tion was quenched with aq sat. NH4Cl solution, poured into aq
NH4Cl solution and extracted with EtOAc (3 × 100 mL). The com-
bined organic phases were washed with brine (25 mL), dried
(MgSO4) and purified by flash chromatography (pentane–
EtOAc, 86:14, then 50:50). The functionalized quinoline 3a
(181 mg, 52%) was obtained as a yellow solid; mp 132 °C.
Ethyl 8-Iodo-4-methyl-2-{[(trifluoromethyl)sulfonyl]oxy}-6-
quinolinecarboxylate (1a)
To a mixture of 7a (6.76 g, 19.0 mmol) and anhyd pyridine (15 mL)
in CH2Cl2 (50 mL) was added Tf2O (22.8 mmol, 3.8 mL) dropwise
at 0 °C. The reaction mixture was stirred for 12 h and allowed to
warm to r.t. After complete conversion, determined by TLC analy-
sis, the mixture was poured into aq sat. NaHCO3 solution (100 mL)
and extracted with Et2O (4 × 300 mL). The combined organic phas-
es were washed with brine (100 mL), dried (Na2SO4) and concen-
trated. The product 1a (7.31 g, 79%) precipitated as light brown
solid, which was filtered, and washed with a small amount of Et2O.
The filtrate was purified by flash chromatography (pentane–
EtOAc, 67:33) to yield a further amount of 1a (577 mg, 6%; total
yield: 7.89 g, 85%); mp 176 °C.
IR (KBr): 3437 (m), 2965 (w), 1715 (s), 1592 (m), 1512 (s), 1418
(s), 1224 (s), 1174 (m), 1136 (s), 1033 (m), 974 (s), 863 (m), 824
(m), 769 (m), 613 (m) cm–1.
1H NMR (300 MHz, CDCl3): δ = 8.69 (d, 1 H, J = 1.8 Hz, ArH-5),
8.43 (d, 1 H, J = 1.8 Hz, ArH-7), 7.41 (dm, 2 H, J = 8.6 Hz, ArH-
2′,6′), 7.11–7.09 (m, 1 H, ArH-3), 6.85 (dm, 2 H, J = 8.6 Hz, ArH-
3′,5′), 6.59 (d, 1 H, J = 5.3 Hz, CHOH), 4.46 (q, 2 H, J = 7.1 Hz,
CO2CH2CH3), 3.77 (s, 3 H, OCH3), 2.83 (d, 3 H, J = 0.9 Hz,
ArCH3), 1.45 (t, 3 H, J = 7.1 Hz, CO2CH2CH3).
IR (KBr): 3436 (m), 1714 (m), 1420 (m), 1276 (m), 1231 (m), 1128
(w), 979 (w), 862 (w), 831 (w), 765 (w), 607 (w) cm–1.
1H NMR (300 MHz, CDCl3): δ = 8.94 (d, 1 H, J = 1.8 Hz, ArH-7),
8.74 (d, 1 H, J = 1.8 Hz, ArH-5), 7.18–7.16 (m, 1 H, ArH-3), 4.48
(q, 2 H, J = 7.1 Hz, CO2CH2CH3), 2.85 (d, 3 H, J = 0.9 Hz, ArCH3),
1.47 (t, 3 H, J = 7.1 Hz, CO2CH2CH3).
13C NMR (75 MHz, CDCl3): δ = 164.8, 158.0, 153.0, 152.8, 144.1,
141.5, 133.9, 128.0, 127.5, 126.9, 126.4, 124.9, 117.5 (q,
JCF = 320.4 Hz), 112.7, 112.5, 71.8, 60.7, 54.2, 18.6, 13.3.
MS (EI): m/z (%) = 499 (M+, 0.2), 367 (17), 366 (74), 259 (16), 258
(100), 230 (34), 135 (11).
HRMS: m/z calcd for C22H20F3NO7S: 498.0834 [M – H]+; found:
13C NMR (75 MHz, CDCl3): δ = 164.5, 155.4, 154.0, 147.6, 141.1,
130.1, 127.2, 127.0, 120.8, 115.0, 101.9, 62.0, 19.3, 14.3.
498.0841 [M – H]+.
MS (EI): m/z (%) = 489 (M+, 100), 461 (10), 444 (29), 380 (12), 328
(23), 300 (12), 173 (15), 129 (14), 128 (18), 69 (11).
Ethyl 8-Bromo-4-methyl-2-{[(trifluoromethyl)sulfonyl]oxy}-6-
quinolinecarboxylate (3b)
HRMS: m/z calcd for C14H11F3INO5S: 488.9355; found: 488.9388.
Compound 3b was synthesized following the typical procedure as
described for compound 3a by reacting 1a (489 mg, 1.0 mmol) with
i-PrMgCl (0.94 M, 1.17 mL, 1.1 mmol) for 15 min at –30 °C. 1,2-
Dibromo-1,1,2,2-tetrachloroethane (977 mg, 3.00 mmol) dissolved
in THF (1 mL) was then added, the cooling bath was removed and
the reaction mixture was stirred at r.t. The conversion was complete
after 1.5 h. After workup and purification by flash chromatography
(pentane–EtOAc, 88:12), 3b (344 mg, 78%) was obtained as a
white solid; mp 182 °C.
Anal. Calcd for C14H11F3INO5S (489.21): C, 34.37; H, 2.27; N,
2.86. Found: C, 34.55; H, 2.22; N, 2.89.
8-Iodo-4-methyl-6-(trifluoromethyl)-2-quinolinyl Trifluoro-
methanesulfonate (1b)
To a mixture of 7b (662 mg, 1.88 mmol) and anhyd pyridine (437
mg, 5.50 mmol) in CH2Cl2 (5 mL) was added Tf2O (2.21 mmol,
0.37 mL) dropwise at 0 °C. The reaction mixture was stirred for 13
h and allowed to warm to r.t. After complete conversion, deter-
mined by GC, the mixture was poured into aq sat. NaHCO3 solution
(100 mL) and extracted with Et2O (3 × 100 mL). The combined or-
ganic phases were washed with brine (100 mL), dried (Na2SO4) and
concentrated under reduced pressure. The product 1b (910 mg,
99%) was obtained as pale yellow solid; mp 112 °C.
IR (KBr): 3430 (w), 1712 (s), 1592 (m), 1456 (w), 1420 (m), 1388
(m), 1328 (w), 1279 (s), 1231 (s), 1209 (m), 1128 (m), 980 (m), 918
(w), 864 (m), 837 (m), 806 (w), 766 (w), 737 (w), 607 (m) cm–1.
1H NMR (300 MHz, CDCl3): δ = 8.72 (d, 1 H, J = 1.8 Hz, ArH-5),
8.69 (d, 1 H, J = 1.8 Hz, ArH-7), 7.21–7.18 (m, 1 H, ArH-3), 4.48
(q, 2 H, J = 7.1 Hz, CO2CH2CH3), 2.85 (d, 3 H, J = 0.9 Hz, ArCH3),
1.47 (t, 3 H, J = 7.1 Hz, CO2CH2CH3).
13C NMR (75 MHz, CDCl3): δ = 163.7, 154.4, 152.8, 144.5, 133.2,
128.6, 127.1, 125.0, 123.9, 119.8, 114.0, 61.0, 18.5, 14.5.
MS (EI): m/z (%) = 443/441 (M+, 100/99), 415 (20), 413 (20), 398
(47), 396 (45), 334 (31), 332 (31), 282 (16), 280 (16), 254 (22), 252
(21), 236 (10), 229 (11), 210 (10), 208 (15), 157 (12), 156 (10), 129
(19), 128 (28), 101 (13), 69 (19).
IR (KBr): 3436 (w), 1601 (w), 1460 (w), 1424 (m), 1393 (m), 1293
(s), 1218 (s), 1129 (s), 1091 (m), 981 (m), 889 (m), 857 (m), 796
(m), 765 (w), 656 (w) cm–1.
1H NMR (300 MHz, CDCl3): δ = 8.54 (d, 1 H, J = 1.8 Hz, ArH-7),
8.32–8.29 (m, 1 H, ArH-5), 7.23–7.21 (m, 1 H, ArH-3), 2.84 (d,
3 H, J = 0.9 Hz, CH3).
13C NMR (75 MHz, CDCl3): δ = 155.5, 153.5, 147.0, 137.3 (q,
J
CF = 2.9 Hz), 130.2 (q, JCF = 33.5 Hz), 127.0, 122.2 (q, JCF = 4.1
HRMS: m/z calcd for C14H11BrF3NO5S: 440.9493; found:
440.9496.
Hz), 120.9 (q, JCF = 5.3 Hz), 116.6, 115.6, 103.1, 19.2.
MS (EI): m/z (%) = 485 (M+, 100), 421 (20), 324 (26), 294 (12), 266
(10), 225 (12), 198 (11), 197 (93), 196 (12), 176 (10), 170 (10), 169
(15), 147 (11), 69 (21).
Anal. Calcd for C14H11BrF3NO5S (442.21): C, 38.03; H, 2.51; N,
3.17. Found: C, 37.94; H, 2.48; N, 3.17.
HRMS: m/z calcd for C12H6F6INO3S: 484.9017; found: 484.9002.
Ethyl 8-Allyl-4-methyl-2-{[(trifluoromethyl)sulfonyl]oxy}-6-
quinolinecarboxylate (3c)
Ethyl 8-[Hydroxy(4-methoxyphenyl)methyl]-4-methyl-2-{[(tri-
fluoromethyl)sulfonyl]oxy}-6-quinolinecarboxylate (3a); Typi-
cal Procedure
To a mixture of 1a (342 mg, 0.70 mmol) and tetradecane (3 drops,
internal standard) in THF (1 mL) at –30 °C was added i-PrMgCl
Compound 3c was synthesized following the typical procedure as
described for compound 3a by reacting 1a (3.42 g, 7.00 mmol) with
i-PrMgCl (0.94 M, 8.2 mL, 7.7 mmol) for 10 min at –30 °C. Follow-
ing the addition of CuCN 2LiCl (1.0 M, 7.7 mL, 7.7 mmol), allyl
bromide (2.54 g, 21.0 mmol) was added as the electrophile. The
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A. Staubitz et al.
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cooling bath was removed and the reaction mixture was stirred at r.t.
After 1 h, the mixture was worked up and purified by flash chroma-
tography (pentane–EtOAc, 93:7) to yield 3c (2.16 g, 77%) as an or-
ange solid; mp 81 °C.
material was completely consumed (determined by TLC analysis).
Workup and purification by flash chromatography (pentane–
EtOAc, 93:7) afforded 3e (142 mg, 41%) as a yellow solid; mp
140 °C.
IR (KBr): 3414 (w), 3073 (w), 2990 (w), 1716 (vs), 1590 (s), 1515
(m), 1460 (m), 1418 (vs), 1323 (m), 1282 (s), 1230 (s), 1130 (s),
1031 (m), 1011 (m), 981 (s), 928 (m), 912 (m), 868 (s), 834 (m), 802
(w), 792 (m), 754 (m), 676 (w), 608 (s), 504 (w) cm–1.
IR (KBr): 3432 (m), 2984 (m), 2936 (w), 1723 (s), 1692 (s), 1589
(m), 1509 (m), 1459 (m), 1419 (s), 1370 (m), 1286 (s), 1224 (s),
1158 (s), 1132 (s), 1021 (m), 974 (s), 910 (w), 858 (m), 830 (m),
767 (m), 682 (w), 600 (m), 510 (w) cm–1.
1H NMR (300 MHz, CDCl3): δ = 8.64 (d, 1 H, J = 1.8 Hz, ArH-5),
8.23 (d, 1 H, J = 1.8 Hz, ArH-7), 7.14–7.11 (m, 1 H, ArH-3), 6.19–
6.05 (m, 1 H, CH2CH=CH2), 5.21–5.13 (m, 1 H, CH2CH=CHtransH),
5.13–5.07 (m, 1 H, CH2CH=CHcisH), 4.47 (q, 2 H, J = 7.1 Hz,
CO2CH2CH3), 3.95 (d, 2 H, J = 6.6 Hz, CH2CH=CH2), 2.83 (d, 3 H,
J = 0.9 Hz, ArCH3), 1.46 (t, 3 H, J = 7.1 Hz, CO2CH2CH3).
1H NMR (300 MHz, CDCl3): δ = 8.76 (d, 1 H, J = 1.4 Hz, ArH-5),
8.64 (d, 1 H, J = 1.4 Hz, ArH-7), 8.59 (d, 1 H, J = 16.1 Hz,
ArCH=CH), 7.19 (s, 1 H, ArH-3), 6.71 (d, 1 H, J = 16.1 Hz,
ArCH=CH), 4.50 (q, 2 H, J = 7.2 Hz, CO2CH2CH3), 2.86 (s, 3 H,
ArCH3), 1.58 [s, 9 H, C(CH3)3], 1.48 (t, 3 H, J = 7.2 Hz,
CO2CH2CH3).
13C NMR (75 MHz, CDCl3): δ = 166.0, 154.4, 153.2, 146.3, 140.3,
136.4, 129.9, 128.9, 127.3, 124.8, 120.8, 116.6, 113.6, 61.6, 35.6,
19.5, 14.4.
13C NMR (75 MHz, CDCl3): δ = 165.7, 165.4, 154.7, 153.3, 145.6,
137.6, 134.0, 129.0, 128.1, 127.6, 127.5, 124.2, 118.7 (q,
JCF = 321.6 Hz), 114.4, 80.7, 61.9, 28.1, 19.5, 14.4.
MS (EI): m/z (%) = 403 (M+, 28), 358 (21), 270 (65), 242 (29), 240
(19), 226 (14), 209 (14), 208 (17), 207 (77), 198 (100), 197 (64),
196 (20), 180 (28), 168 (28), 167 (30), 154 (16), 69 (17), 64 (15).
MS (EI): m/z (%) = 489 (M+, 1), 416 (15), 388 (21), 257 (16), 256
(100), 255 (28), 228 (15), 210 (36), 154 (19), 57 (55).
HRMS: m/z calcd for C21H22F3NO7S: 489.1069; found: 489.1078.
HRMS: m/z calcd for C17H16F3NO5S: 403.0701; found: 403.0693.
Anal. Calcd for C21H22F3NO7S (489.46): C, 51.53; H, 4.53; N, 2.86.
Anal. Calcd for C17H16F3NO5S (403.37): C, 50.62; H, 4.00; N, 3.47.
Found: C, 50.62; H, 4.06; N, 3.53.
Found: C, 51.18; H, 4.78; N, 2.70.
Ethyl 4-Methyl-8-(prop-2-ynyl)-2-{[(trifluoromethyl)sulfon-
yl]oxy}-6-quinolinecarboxylate (3f)
8-Allyl-4-methyl-6-(trifluoromethyl)-2-quinolinyl Trifluoro-
methanesulfonate (3d)
Compound 3f was synthesized following the typical procedure as
described for compound 3a by reacting 1a (342 mg, 0.70 mmol)
with i-PrMgCl (0.94 M, 0.82 mL, 0.77 mmol) for 25 min at –30 °C.
Following the addition of CuCN 2LiCl (1.0 M, 0.77 mL, 0.77
mmol), propargyl bromide (250 mg, 2.10 mmol) was added as the
electrophile, the cooling bath was removed and the mixture was
stirred at r.t. After 30 min the reaction mixture was quenched with
aq sat. NH4Cl solution. Workup and purification by flash chroma-
tography (pentane–EtOAc, 93:7) gave the quinoline derivative 3f
(196 mg, 70%) as a pale yellow solid. The product was contaminat-
ed with the corresponding allene (approximately 10%, determined
by 1H NMR spectroscopy); mp 118 °C.
Compound 3d was synthesized following the typical procedure as
described for compound 3a by reacting 1b (445 mg, 0.92 mmol)
with i-PrMgCl (0.94 M, 1.07 mL, 1.01 mmol) for 40 min at –30 °C.
Following the addition of CuCN 2LiCl (1.0 M, 1.01 mL, 1.01
mmol), allyl bromide (333 mg, 2.75 mmol) was added as the elec-
trophile, the cooling bath was removed and the reaction mixture was
stirred at r.t. for 1 h. Workup and purification by flash chromatog-
raphy (pentane–EtOAc, 95:5) yielded 3d (366 mg, 70%) as a pale
yellow solid; mp 81 °C.
IR (KBr): 3436 (w), 1594 (w), 1515 (w), 1466 (w), 1416 (m), 1307
(m), 1245 (m), 1220 (m), 1166 (m), 1128 (s), 1094 (m), 972 (m),
932 (w), 869 (w), 804 (w), 666 (w), 610 (w) cm–1.
1H NMR (300 MHz, CDCl3): δ = 8.19 (s, 1 H, ArH-5), 7.84–7.80
(m, 1 H, ArH-7), 7.19–7.17 (m, 1 H, ArH-3), 6.18–6.03 (m, 1 H,
CH2CH=CH2), 5.23–5.16 (m, 1 H, CH2CH=CHtransH), 5.18–5.12
(m, 1 H, CH2CH=CHcisH), 3.98 (d, 2 H, J = 6.6 Hz, CH2CH=CH2),
2.83 (d, 3 H, J = 0.9 Hz, CH3).
IR (KBr): 3278 (m), 2998 (w), 1708 (s), 1597 (m), 1513 (m), 1460
(m), 1422 (s), 1325 (m), 1302 (s), 1261 (s), 1209 (vs), 1170 (m),
1128 (s), 1029 (m), 983 (s), 914 (w), 858 (m), 827 (s), 770 (m), 752
(m), 674 (m), 601 (s), 511 (m) cm–1; for the isomeric allene: 1956
cm–1.
1H NMR (300 MHz, CDCl3): δ = 8.69–8.65 (m, 1 H, ArH-7), 8.65–
8.60 (m, 1 H, ArH-5), 7.15–7.13 (m, 1 H, ArH-3), 4.48 (q, 2 H,
J = 7.1 Hz, CO2CH2CH3), 4.16 (d, 2 H, J = 3.1 Hz, CH2C≡CH),
2.84 (d, 3 H, J = 0.9 Hz, ArCH3), 2.32 (t, 1 H, J = 3.1 Hz,
CH2C≡CH), 1.47 (t, 3 H, J = 7.1 Hz, CO2CH2CH3); for the isomeric
allene: δ = 5.30 (2 dm, 2 H, J = 6.6 Hz, CH=C=CH2).
13C NMR (75 MHz, CDCl3): δ = 165.8, 154.4, 153.3, 145.6, 135.7,
129.4, 129.0, 127.0, 125.4, 118.7 (q, JCF = 321.0 Hz), 113.9, 80.9,
71.8, 61.7, 20.8, 19.4, 14.4; for the isomeric allene: δ = 210.9.
MS (EI): m/z (%) = 401 (M+, 20), 356 (13), 269 (13), 268 (68), 241
(17), 240 (100), 211 (16), 195 (13), 167 (24), 166 (19), 139 (15).
13C NMR (75 MHz, CDCl3): δ = 154.4, 152.7, 145.5, 141.6, 135.8,
129.1 (q, JCF = 32.9 Hz), 127.1, 126.0 (q, JCF = 2.9 Hz), 121.4 (q,
JCF = 93.3 Hz), 119.9 (q, JCF = 4.7 Hz), 117.2, 116.6, 114.2, 35.5,
19.4.
MS (EI): m/z (%) = 399 (M+, 28), 380 (11), 267 (35), 266 (100), 265
(17), 264 (28), 248 (15), 236 (23), 235 (16), 222 (18), 197 (13), 69
(12).
HRMS: m/z calcd for C15H11F6NO3S: 399.0364; found: 399.0398.
Anal. Calcd for C15H11F6NO3S (399.31): C, 45.12; H, 2.78; N, 3.15.
Found: C, 45.37; H, 2.87; N, 3.50.
HRMS: m/z calcd for C17H14F3NO5S: 401.0545; found: 401.0547.
Ethyl 8-[(1E)-3-tert-butoxy-3-oxoprop-1-enyl]-4-methyl-2-
{[(trifluoromethyl)sulfonyl]oxy}-6-quinolinecarboxylate (3e)
Compound 3e was synthesized following the typical procedure as
described for compound 3a by reacting 1a (342 mg, 0.70 mmol) at
–30 °C with i-PrMgCl (0.94 M, 0.82 mL, 0.77 mmol) for 15 min.
Following the addition of CuCN 2LiCl (1.0 M, 0.77 mL, 0.77
mmol), tert-butyl propiolate (132 mg, 1.05 mmol) in THF (1 mL)
was added very slowly over 5 min. After 1 h the reaction mixture
was allowed to warm to r.t. and stirred for 3.5 h until the starting
Anal. Calcd for C17H14F3NO5S (401.36): C, 50.87; H, 3.52; N, 3.49.
Found: C, 50.63; H, 3.56; N, 3.46.
Ethyl 8-[4-(Ethoxycarbonyl)phenyl]-4-methyl-2-{[(trifluoro-
methyl)sulfonyl]oxy}-6-quinolinecarboxylate (3g); Typical
Procedure
Compound 1b was dissolved in THF (2 mL) with tetradecane as an
internal standard and the reaction mixture was cooled to –30 °C. i-
PrMgBr (0.94 M, 0.82 mL, 0.77 mmol) was added and the mixture
Synthesis 2003, No. 2, 233–242 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Functionalization of Quinolines in Positions 2 and 8
239
was stirred for 30 min, then ZnCl2 (1.5 M, 0.51 mL, 0.77 mmol)
was added and the temperature was allowed to warm to r.t. (mixture
A). In a syringe, the active catalyst was preformed from Pd(dba)2
(1 mol%, 3.45 mg, 6 µmol) and tfp (2 mol%, 2.8 mg, 12 µmol) in
THF (1 mL) and added to ethyl 4-iodobenzoate (190 mg,
0.70 mmol). To this was canulated mixture A and the reaction mix-
ture was stirred for 1.5 h at r.t. Then the mixture was quenched with
aq sat. NH4Cl solution, poured into aq NH4Cl solution (100 mL)
and extracted with EtOAc (3 × 100 mL). The combined extracts
were washed with brine (100 mL), dried (MgSO4), and concentrat-
ed under reduced pressure. Purification by flash chromatography
(pentane–EtOAc, 86:14) yielded the product 3g (307 mg, 74%) as a
white solid; mp 152 °C.
Ethyl 4-Methyl-8-(2-pyrimidinyl)-2-{[(trifluoromethyl)sulfo-
nyl]oxy}-6-quinolinecarboxylate (3i)
Compound 3i was synthesized following the typical procedure as
described for compound 3g by reacting 1a (342 mg, 0.70 mmol)
with i-PrMgCl (0.94 M, 0.82 mL, 0.77 mmol) for 10 min at –30 °C.
Following the addition of ZnCl2 (1.0 M, 0.77 mL, 0.77 mmol) the
reaction mixture was warmed to r.t. (mixture A). The catalyst was
preformed from Pd(dba)2 (6 mol%, 20.7 mg, 36 µmol) and tfp
(12 mol%, 16.8 mg, 72 µmol) in THF (1 mL) and added to 2-
iodopyrimidine11 (122 mg, 0.6 mmol). To this solution was canulat-
ed mixture A and the reaction mixture was stirred for 4 h at r.t. Then
the reaction was quenched with aq sat. NH4Cl solution and worked
up in the usual way. Purification by flash chromatography (pen-
tane–EtOAc, 86:14) yielded 3i (128 mg, 48%) as a pale yellow sol-
id; mp 151 °C.
IR (KBr): 3436 (m), 1719 (m), 1610 (w), 1416 (m), 1285 (m), 1220
(m), 1108 (m), 974 (w), 865 (w), 817 (w), 767 (w) cm–1.
IR (KBr): 3432 (m), 3072 (w), 2987 (w), 1711 (s), 1593 (m), 1569
(m), 1559 (s), 1420 (s), 1401 (s), 1300 (m), 1278 (s), 1227 (vs),
1137 (s), 1026 (w), 962 (s), 912 (w), 871 (m), 834 (m), 767 (m), 752
(m), 713 (w), 679 (m), 651 (w), 609 (m) cm–1.
1H NMR (300 MHz, CDCl3): δ = 8.93 (d, 2 H, J = 4.9 Hz, ArH-
3′,5′), 8.89 (d, 1 H, J = 1.8 Hz, ArH-7), 8.86 (d, 1 H, J = 1.8 Hz,
ArH-5), 7.37 (t, 1 H, J = 4.9 Hz, ArH-4′), 7.16–7.13 (m, 1 H, ArH-
3), 4.47 (q, 2 H, J = 7.1 Hz, CO2CH2CH3), 2.88 (d, 3 H, J = 0.9 Hz,
ArCH3), 1.44 (t, 3 H, J = 7.1 Hz, CO2CH2CH3).
1H NMR (300 MHz, CDCl3): δ = 8.80 (d, 1 H, J = 1.8 Hz, ArH-7),
8.43 (d, 1 H, J = 1.8 Hz, ArH-5), 8.16 (dm, 2 H, J = 8.4 Hz, ArH-
2′,6′), 7.75 (dm, 2 H, J = 8.4 Hz, ArH-3′,5′), 7.18–7.15 (m, 1 H,
ArH-3), 4.50 (q, 2 H, J = 7.1 Hz, ArCO2CH2CH3), 4.43 (q, 2 H,
J = 7.1 Hz, Ar′CO2CH2CH3), 2.89 (d, 3 H, J = 0.9 Hz, ArCH3), 1.47
(t, 3 H, J = 7.1 Hz, ArCO2CH2CH3), 1.44 (t, 3 H, J = 7.1 Hz,
Ar′CO2CH2CH3).
13C NMR (75 MHz, CDCl3): δ = 166.6, 165.7, 154.7, 153.2, 145.3,
142.1, 140.4, 131.2, 130.7, 129.8, 129.0, 128.9, 127.8, 126.4, 118.5
(q, JCF = 319.8 Hz), 114.1, 61.8, 61.0, 19.7, 14.3.
13C NMR (75 MHz, CDCl3): δ = 165.5, 165.3, 156.9, 155.1, 153.0,
145.7, 138.9, 131.5, 128.7, 127.8, 127.6, 119.4, 118.4 (q,
MS (EI): m/z (%) = 511 (M+, 22), 466 (29), 380 (11), 379 (44), 378
(100), 350 (40), 334 (19), 332 (15), 306 (39), 305 (12), 278 (23),
260 (18), 234 (13), 233 (10), 204 (24), 203 (11).
JCF = 321.0 Hz), 113.9, 61.8, 19.5, 14.3.
MS (EI): m/z (%) 396 ([M – OEt]+, 5), 309 (22), 308 (100), 280 (29).
HRMS: m/z calcd for C23H20F3NO7S: 511.0913; found: 511.0897.
HRMS: m/z calcd for C18H14F3N3O5S: 442.0685 [M + H]+ ; found:
442.0712 [M + H]+.
Anal. Calcd for C23H20F3NO7S (511.47): C, 54.01; H, 3.94; N, 2.74.
Found: C, 53.85; H, 3.90; N, 2.76.
Anal. Calcd for C18H14F3N3O5S (441.38): C, 48.98; H, 3.20; N,
9.52. Found: C, 49.06; H, 3.10; N, 9.36.
Ethyl 4-(4-Methyl-6-(trifluoromethyl)-2-{[(trifluoromethyl)-
sulfonyl]oxy}-8-quinolinyl)benzoate (3h)
Ethyl 8-Allyl-2-ethyl-4-methyl-6-quinolinecarboxylate (4a)
According to the typical procedure described for compound 3g, the
active catalyst was preformed from Pd(dba)2 (1 mol%, 2.9 mg, 5
µmol) and tfp (2 mol%, 2.3 mg, 10 µmol) in THF (0.7 mL) and add-
ed to 3c (202 mg, 0.50 mmol). To this mixture was canulated Et2Zn
(1.0 M in Et2O, 1.05 mL, 1.05 mmol) and the reaction mixture was
stirred for 35 min at r.t., then quenched with aq sat. NH4Cl solution.
Workup in the usual way and purification by flash chromatography
(pentane–EtOAc, 96:4) yielded the product 4a (115 mg, 82%) as a
white solid; mp 69 °C.
Compound 3h was synthesized following the typical procedure as
described for compound 3g by reacting 1b (400 mg, 0.83 mmol)
with i-PrMgCl (0.94 M, 0.97 mL, 0.91 mmol) for 40 min at –30 °C.
After the addition of ZnBr2 (1.5 M, 0.61 mL, 0.91 mmol), the reac-
tion mixture was warmed to r.t. (mixture A). The catalyst was pre-
formed from Pd(dba)2 (2 mol%, 7.9 mg, 14 µmol) and tfp (4 mol%,
6.38 mg, 28 µmol) in THF (1 mL) and added to ethyl 4-iodoben-
zoate (190 mg, 0.69 mmol). To this solution was canulated mixture
A and the reaction mixture was stirred for 3.5 h at r.t., then
quenched with aq sat. NH4Cl solution and worked up in the usual
way. Purification by flash chromatography (pentane–EtOAc, 97:3)
yielded the product 3h (221 mg, 63%) as a white solid; mp 128 °C.
IR (KBr): 3426 (w), 2977 (m), 2933 (w), 1713 (vs), 1604 (m), 1570
(w), 1497 (w), 1468 (w), 1418 (m), 1366 (w), 1271 (s), 1240 (m),
1222 (m), 1199 (m), 1144 (w), 1114 (w), 1033 (m), 995 (w), 915
(m), 904 (m), 869 (w), 766 (m), 512 (w) cm–1.
1H NMR (300 MHz, CDCl3): δ = 8.59 (d, 1 H, J = 1.8 Hz, ArH-5),
8.11 (d, 1 H, J = 1.8 Hz, ArH-7), 7.18–7.15 (m, 1 H, ArH-3), 6.29–
6.14 (m, 1 H, CH2CH=CH2), 5.24–5.16 (m, 1 H, CH2CH=CHtransH),
5.11–5.06 (m, 1 H, CH2CH=CHcisH), 4.45 (q, 2 H, J = 7.1 Hz,
CO2CH2CH3), 4.09 (d, 2 H, J = 6.6 Hz, CH2CH=CH2), 2.97 (q, 2 H,
J = 7.5 Hz, ArCH2CH3), 2.72 (d, 3 H, J = 0.9 Hz, ArCH3), 1.45 (t, 3
H, J = 7.1 Hz, CO2CH2CH3), 1.41 (t, 3 H, J = 7.5 Hz, ArCH2CH3).
IR (KBr): 3436 (m), 2987 (w), 1706 (s), 1610 (m), 1465 (m), 1418
(s), 1370 (m), 1284 (s), 1225 (s), 1132 (s), 1062 (m), 1024 (m), 976
(m), 898 (m), 865 (m), 802 (m), 766 (m), 708 (m), 653 (m), 607 (m)
cm–1.
1H NMR (300 MHz, CDCl3): δ = 8.37–8.34 (m, 1 H, ArH-7), 8.16
(d, 2 H, J = 8.8 Hz, ArH-2′,6′), 8.02 (d, 1 H, J = 1.8 Hz, ArH-5),
7.74 (d, 2 H, J = 8.8 Hz, ArH-3′,5′), 7.22 (d, 1 H, J = 0.9 Hz, ArH-
3), 4.43 (q, 2 H, J = 7.1 Hz, CO2CH2CH3), 2.88 (d, 3 H, J = 0.9 Hz,
ArCH3), 1.44 (t, 3 H, J = 7.1 Hz, CO2CH2CH3).
13C NMR (75 MHz, CDCl3): δ = 166.8, 164.5, 148.0, 145.5, 139.6,
137.6, 127.7, 126.5, 126.0, 125.0, 122.4, 115.7, 61.1, 36.0, 32.1,
19.0, 14.4, 13.1.
13C NMR (75 MHz, CDCl3): δ = 166.4, 154.7, 152.7, 141.6, 141.4,
130.7, 130.2, 130.1, 129.9 (q,
JCF = 19.4 Hz), 129.6 (q,
J
CF = 33.5Hz), 127.7, 127.3 (q, JCF = 2.9 Hz), 127.2, 121.5 (q,
MS (EI): m/z (%) = 283 (M+, 58), 282 (22), 269 (20), 268 (100), 254
(23), 241 (11), 240 (63), 238 (18), 225 (14), 210 (13), 195 (15), 180
(10).
JCF = 4.1 Hz), 118.5 (q, JCF = 321.0 Hz), 114.6, 61.1, 19.5, 14.3.
MS (EI): m/z (%) = 507 (M+, 18), 462 (16), 374 (38), 346 (43), 330
(11), 328 (17), 303 (19), 392 (100), 301 (25), 300 (11).
HRMS: m/z calcd for C18H21NO2: 283.1572; found: 283.1582.
HRMS: m/z calcd for C21H15F6NO5S: 507.0575; found: 507.0577.
Anal. Calcd for C18H21NO2 (283.36): C, 76.29; H, 7.47; N, 4.94.
Found: C, 76.29; H, 7.31; N, 4.92.
Synthesis 2003, No. 2, 233–242 ISSN 0039-7881 © Thieme Stuttgart · New York

240
A. Staubitz et al.
PAPER
Ethyl 8-Allyl-2-(4-methoxyphenyl)-4-methyl-6-quinolinecar-
boxylate (4b)
(q, JCF = 3.5 Hz), 124.1, 123.3 (q, JCF = 4.1 Hz), 118.3, 115.0, 60.3,
35.2, 18.4, 13.4.
To a solution of 4-iodoanisole (342 mg, 0.70 mmol) in THF (0.2
mL), was added slowly n-BuLi (1.7 M in hexane, 0.7 mL,
1.2 mmol) at –78 °C and the reaction mixture was stirred for
30 min. ZnCl2 (1.0 M, 1.2 mL, 1.2 mmol) was then added and the
mixture was warmed to r.t. and stirred for a further 30 min (mixture
A). According to the typical procedure described for compound 3g,
the active catalyst was preformed from Pd(dba)2 (1 mol%, 2.9 mg,
5 µmol) and tfp (2 mol%, 2.3 mg, 10 µmol) in THF (0.7 mL) and
added to 3c (202 mg, 0.50 mmol). To this was canulated mixture A,
the reaction mixture was stirred for 1.25 h at r.t., then quenched with
aq sat. NH4Cl solution. Workup in the usual way and purification by
flash chromatography (pentane–EtOAc, 96:4) yielded the product
4b (173 mg, 96%) as a pale brown solid; mp 99 °C.
MS (EI): m/z (%) = 399 (M+, 38), 398 (100), 184 (33), 370 (26), 356
(41), 326 (11).
HRMS: m/z calcd for C23H20F3NO2: 398.1368 [M – H]+; found:
398.1406 [M – H]+.
Ethyl 8-Allyl-2-[4-(ethoxycarbonyl)phenyl]-4-methyl-6-quino-
linecarboxylate (4d)
To a solution of ethyl 4-iodobenzoate (276 mg, 0.75 mmol) in THF
(1 mL) was added slowly i-PrMgCl (0.94 M, 0.88 mL, 0.83 mmol)
at –30 °C and the reaction mixture was stirred for 30 min. ZnCl2
(1.0 M, 0.83 mL, 0.83 mmol) was added and the mixture was
warmed to r.t. and stirred for a further 30 min (mixture A). Accord-
ing to the typical procedure described for compound 3g, the active
catalyst was preformed from Pd(dba)2 (1 mol%, 2.9 mg, 5 µmol)
and tfp (2 mol%, 2.3 mg, 1 µmol) in THF (0.7 mL) and added to 3c
(202 mg, 0.50 mmol). To this was canulated mixture A and the re-
action mixture was stirred for 1 h at r.t., then quenched with aq sat.
NH4Cl solution. Workup in the usual way and purification by flash
chromatography (pentane–EtOAc, 95:5) yielded the product 4d
(186 mg, 92%) as a white solid; mp 159 °C.
IR (KBr): 3436 (m), 2977 (w), 1705 (s), 1603 (m), 1560 (w), 1496
(w), 1462 (w), 1354 (w), 1252 (m), 1181 (m), 1153 (w), 1035 (w),
901 (w), 833 (w), 764 (w) cm–1.
1H NMR (300 MHz, CDCl3): δ = 8.61 (d, 1 H, J = 2.0 Hz, ArH-5),
8.24 (d, 2 H, J = 8.8 Hz, ArH-2′,6′), 8.14 (d, 1 H, J = 2.0 Hz, ArH-
7), 7.76–7.73 (m, 1 H, ArH-3), 7.04 (d, 2 H, J = 8.8 Hz, ArH-3′,5′),
6.34–6.19 (m,
1 H, CH2CH=CH2), 5.28–5.19 (m, 1 H,
CH2CH=CHtransH), 5.14–5.09 (m, 1 H, CH2CH=CHcisH), 4.46
(q, 2 H, J = 7.1 Hz, CO2CH2CH3), 4.17 (d, 2 H, J = 6.6 Hz,
CH2CH=CH2), 3.90 (s, 3 H, OCH3), 2.80 (d, 3 H, J = 0.9 Hz,
ArCH3), 1.46 (t, 3 H, J = 7.1 Hz, CO2CH2CH3).
13C NMR (75 MHz, CDCl3): δ = 166.8, 161.1, 156.7, 148.3, 146.2,
140.0, 137.7, 131.9, 128.9, 128.1, 126.7, 126.3, 125.1, 119.1, 115.8,
114.2, 61.2, 55.4, 36.1, 19.3, 14.5.
IR (KBr): 3435 (m), 2981 (w), 1717 (s), 1602 (m), 1558 (w), 1496
(w), 1475 (w), 1422 (w), 1366 (w), 1350 (w), 1277 (s), 1222 (m),
1155 (w), 1110 (m), 1026 (m), 911 (w), 862 (w), 776 (m), 709 (w)
cm–1.
1H NMR (300 MHz, CDCl3): δ = 8.65–8.63 (m, 1 H, ArH-5), 8.32
(dm, 2 H, J = 8.4 Hz, ArH-2′, 6′), 8.19 (dm, 2 H, J = 8.4 Hz, ArH-
3′, 5′), 8.17 (s, 1 H, ArH-7), 7.82 (s, 1 H, ArH-3), 6.33–6.18 (m, 1
H, CH2CH=CH2), 5.28–5.19 (m, 1 H, CH2CH=CHtransH), 5.16–5.09
MS (EI): m/z (%) = 361 (M+, 30), 360 (100), 346 (22), 332 (15), 318
(15).
(m, 1 H, CH2CH=CHcisH), 4.47 (q, 2 H, J = 7.1 Hz,
ArCO2CH2CH3), 4.43 (q, 2 H, J = 7.1 Hz, Ar′CO2CH2CH3), 4.18 (d,
2 H, J = 7.1 Hz, CH2CH=CH2), 2.83 (d, 3 H, J = 0.9 Hz, ArCH3),
1.47 (t, 3 H, J = 7.1 Hz, ArCO2CH2CH3), 1.44 (t, 3 H, J = 7.1 Hz,
Ar′CO2CH2CH3).
13C NMR (75 MHz, CDCl3): δ = 166.6, 166.4, 155.8, 148.2, 146.9,
143.3, 140.5, 137.5, 131.2, 130.0, 128.3, 127.6, 127.4, 126.8, 125.1,
119.7, 116.0, 61.3, 61.1, 36.1, 19.4, 14.4, 14.3.
HRMS: m/z calcd for C23H23NO3: 360.1600 [M – H]+; found:
360.1588 [M – H]+.
Anal. Calcd for C23H23NO3 (361.43): C, 76.43; H, 6.41; N, 3.88.
Found: C, 75.41; H, 6.30; N, 3.84.
Ethyl 8-Allyl-4-methyl-2-[3-(trifluoromethyl)phenyl]-6-quino-
linecarboxylate (4c)
To a solution of 1-iodo-3-(trifluoromethyl)benzene (342 mg, 0.70
mmol) in THF (0.2 mL) was added slowly BuLi (1.58 M in hexane,
0.44 mL, 0.70 mmol) at –78 °C and the reaction mixture was stirred
for 30 min. ZnBr2 (1.05 M, 0.70 mL, 0.74 mmol) was added and the
mixture was warmed to r.t. and stirred for 30 min (mixture A). Ac-
cording to the typical procedure described for compound 3g, the ac-
tive catalyst was preformed from Pd(dba)2 (1 mol%, 2.9 mg, 5
µmol) and tfp (2 mol%, 2.3 mg, 10 µmol) in THF (0.7 mL) and add-
ed to 3c (202 mg, 0.50 mmol). To this solution was canulated mix-
ture A and the reaction mixture was stirred for 2 h at r.t., then
quenched with aq sat. NH4Cl solution. Workup in the usual way and
purification by flash chromatography (pentane–EtOAc, 96:4) yield-
ed the product 4c (161 mg, 81%) as a pale yellow solid; mp 105 °C.
MS (EI): m/z (%) = 403 (M+, 32), 402 (100), 388 (17), 374 (11), 346
(11), 332 (14).
HRMS: m/z calcd for C25H25NO4: 402.1705 [M – H]+; found:
402.1694 [M – H]+.
Ethyl 4-[8-Allyl-4-methyl-6-(trifluoromethyl)-2-quinolinyl]-
benzoate (4e)
To a solution of ethyl 4-iodobenzoate (239 mg, 0.86 mmol) in THF
(1 mL) at –30 °C was added slowly i-PrMgCl (0.94 M, 1.01 mL,
0.95 mmol) and the reaction mixture was stirred for 1 h. ZnBr2
(THF, 1.5 M, 0.63 mL, 0.95 mmol) was then added, the mixture
was warmed to r.t. and stirred for a further 30 min (mixture A). Ac-
cording to the procedure described for compound 3g, the active cat-
alyst was preformed from Pd(dba)2 (7 mol%, 32.2 mg, 40 µmol) and
tfp (14 mol%, 18.56 mg, 80 µmol) in THF (0.7 mL) and added to
3d (230 mg, 0.58 mmol). To this solution was canulated mixture A
and the reaction mixture was stirred for 4 h at r.t., then quenched
with aq sat. NH4Cl solution. Workup and purification by flash chro-
matography (pentane–EtOAc, 97:3) yielded the product 4e
(203 mg, 89%) as a white solid; mp 119 °C.
IR (KBr): 3436 (m), 3077 (m), 2982 (m), 1706 (s), 1604 (m), 1564
(w), 1416 (m), 1350 (m), 1328 (s), 1244 (s), 1127 (s), 1076 (m),
1033 (w), 914 (m), 900 (m), 802 (m), 764 (m), 694 (w) cm–1.
1H NMR (300 MHz, CDCl3): δ = 8.64 (d, 1 H, J = 1.8 Hz, ArH-5),
8.51 (s, 1 H, ArH-2′), 8.44 (d, 1 H, J = 8.0 Hz, ArH-4′), 8.20 (d,
1 H, J = 1.8 Hz, ArH-7), 7.80 (s, 1 H, ArH-3), 7.73 (d, 1 H, J = 8.0
Hz, ArH-6′), 7.64 (t, 1 H, J = 8.0 Hz, ArH-5′), 6.30–6.15 (m, 1 H,
CH2CH=CH2), 5.29–5.20 (m, 1 H, CH2CH=CHtransH), 5.17–5.10
(m, 1 H, CH2CH=CHcisH), 4.47 (q, 2 H, J = 7.1 Hz, CO2CH2CH3),
4.17 (d, 2 H, J = 6.6 Hz, CH2CH=CH2), 2.84 (s, 3 H, ArCH3), 1.47
(t, 3 H, J = 7.1 Hz, CO2CH2CH3).
IR (KBr): 3434 (m), 2982 (w), 1716 (s), 1604 (m), 1466 (w), 1421
(m), 1368 (w), 1316 (s), 1271 (s), 1225 (m), 1157 (s), 1121 (s), 1064
(w), 1024 (w), 896 (m), 858 (w), 777 (m), 711 (w) cm–1.
1H NMR (300 MHz, CDCl3): δ = 8.32 (dm, 2 H, J = 8.8 Hz, ArH-
2′,6′), 8,19 (dm, 2 H, J = 8.8 Hz, ArH-3′,5′), 8.17 (s, 1 H, ArH-3),
7.86 (s, 1 H, ArH-5), 7.76–7.73 (m, 1 H, ArH-7), 6.23–6.15 (m, 1
13C NMR (75 MHz, CDCl3): δ = 165.5, 154.4, 147.2, 146.1, 139.5,
139.1, 136.4, 130.4, 130.0, 129.7, 128.3, 127.5, 126.7, 125.8, 125.3
Synthesis 2003, No. 2, 233–242 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Functionalization of Quinolines in Positions 2 and 8
241
H, CH2CH=CH2), 5.29–5.21 (m, 1 H, CH2CH=CHtransH), 5.19–5.13
(m, 1 H, CH2CH=CHcisH), 4.43 (q, 2 H, J = 7.1 Hz, CO2CH2CH3),
4.19 (d, 2 H, J = 6.6 Hz, CH2CH=CH2), 2.81 (d, 3 H, J = 0.9 Hz,
ArCH3), 1.44 (t, 3 H, J = 7.1 Hz, CO2CH2CH3).
13C NMR (75 MHz, CDCl3): δ = 166.3, 155.9, 147.3, (q, JCF = 1.2
Hz), 146.3, 143.1, 141.8, 136.9, 131.6, 130.0, 127.7 (q, JCF = 32.3
Hz), 127.4, 126.6, 124.4 (q, JCF = 2.9 Hz), 122.5, 120.1, 119.9 (q,
JCF = 4.7 Hz), 116.6, 61.1, 36.0, 19.3, 14.3.
1H NMR (300 MHz, CDCl3): δ = 8.41 (d, 1 H, J = 1.8 Hz, ArH-6),
7.61 (d, 1 H, J = 1.8 Hz, ArH-2), 7.23 (s, 1 H, N=CH), 5.90–5.87
(m,
1 H, C=CHCO2CH2CH3), 4.32 (q, 2 H, J = 7.1 Hz,
ArCO2CH2CH3), 4.00 (q, 2 H, J = 7.1 Hz, C=CHCO2CH2CH3),
2.99 (s, 3 H, NCH3), 2.96 (s, 3 H, NCH3), 2.04 (d, 3 H, J = 1.3 Hz,
CCH3), 1.36 (t, 3 H, J = 7.1 Hz, ArCO2CH2CH3), 1.09 (t, 3 H,
J = 7.01 Hz, C=CHCO2CH2CH3).
13C NMR (75 MHz, CDCl3): δ = 165.8, 165.3, 155.5, 153.9, 139.3,
139.3, 133.7, 129.1, 129.1, 125.3, 120.1, 93.5, 60.8, 59.8, 24.5,
14.3, 14.1.
MS (EI): m/z (%) = 399 (M+, 32), 398 (100), 384 (18), 371 (10), 370
(41), 356 (27), 326 (12).
MS (EI): m/z (%) 458 (M+, 9), 386 (18), 385 (100), 357 (13).
HRMS: m/z calcd for C23H20F3NO2: 399.1446; found: 399.1410.
HRMS: m/z calcd for C18H23IN2O4: 458.0703; found: 458.0723.
Anal. Calcd for C23H20F3NO2 (399.41): C, 69.16; H, 5.05; N, 3.51.
Found: C, 69.18; H, 4.93; N, 3.45.
Ethyl (2Z)-3-[2-{[(E)-(Dimethylamino)methylidene]amino}-3-
iodo-5-(trifluoromethyl)phenyl]but-2-enoate (6b)
Ethyl 4-[2-Ethyl-4-methyl-6-(trifluoromethyl)-8-quinolinyl]-
benzoate (4f)
Compound 6b was synthesized following the same procedure as de-
scribed for compound 6a by reacting compound 5b (1.87 g, 4.0
mmol) with i-PrMgCl (0.94 M, 4.68 mL, 4.4 mmol) for 30 min at
–30 °C. Following the addition of CuCN 2LiCl (1.0 M, 4.4 mL, 4.4
mmol), ethyl (Z)-3-iodobut-2-enoate (1.44 g, 6.0 mmol) was added
as the electrophile, the cooling bath was removed and the mixture
was stirred at r.t. for 3.5 h. Workup and flash chromatography (pen-
tane–EtOAc, 90:10) yielded 6b (1.49 g, 82%) as a yellow oil.
According to the typical procedure described for compound 3g, the
active catalyst was preformed from Pd(dba)2 (3 mol%, 5.8 mg, 10
µmol) and tfp (6 mol%, 4.6 mg, 20 µmol) in THF (0.7 mL) and add-
ed to 3h (160 mg, 0.32 mmol). To this mixture was canulated Et2Zn
(1.0 M in Et2O, 0.47 mL, 0.47 mmol) and the reaction mixture was
stirred for 30 min at r.t., then quenched with aq sat. NH4Cl solution.
Workup in the usual way and purification by flash chromatography
(pentane–EtOAc, 97:3) yielded the product 4f (106 mg, 84%) as a
pale yellow solid; mp 86 °C.
IR (film): 2981 (m), 2938 (m), 1715 (s), 1645 (vs), 1593 (s), 1435
(s), 1415 (m), 1371 (s), 1305 (vs), 1241 (s), 1203 (s), 1121 (s), 1076
(s), 1047 (s), 887 (m), 771 (m), 686 (m) cm–1.
1H NMR (300 MHz, CDCl3): δ = 7.97–7.94 (m, 1 H, ArH-4), 7.21
(s, 1 H, ArH-6), 7.19–7.15 (m, 1 H, N=CH), 5.91–5.87 (m, 1 H,
C=CHCO2CH2CH3), 4.00 (q, J = 7.1 Hz, 2 H, CO2CH2CH3), 2.97
(s, 3 H, NCH3), 2.96 (s, 3 H, NCH3), 2.04 (d, J = 1.3 Hz, 3 H,
CCH3), 1.07 (t, J = 7.1 Hz, 3 H, CO2CH2CH3).
IR (KBr): 3416 (m), 2982 (m), 2936 (m), 1714 (vs), 1610 (s), 1570
(m), 1471 (m), 1416 (s), 1369 (m), 1312 (s), 1276 (vs), 1213 (m),
1186 (s), 1160 (vs), 1122 (vs), 1058 (m), 1023 (m), 897 (s), 858 (s),
809 (m), 772 (m), 710 (s), 630 (w), 507 (w) cm–1.
1H NMR (300 MHz, CDCl3): δ = 8.28 (s, 1 H, ArH-7), 8.16 (dm, 2
H, J = 8.4 Hz, ArH-2′,6′), 7.91–7.88 (dm, 1 H, J = 1.8 Hz, ArH-5),
7.84 (d, 2 H, J = 8.4 Hz, ArH-3′,5′), 7.25 (s, 1 H, ArH-3), 4.43 (q, 2
H, J = 7.1 Hz, CO2CH2CH3), 2.92 (q, 2 H, J = 7.5 Hz, ArCH2CH3),
2.75 (s, 3 H, ArCH3), 1.44 (t, 3 H, J = 7.1 Hz, CO2CH2CH3), 1.33
(t, 3 H, J = 7.5 Hz, ArCH2CH3).
13C NMR (75 MHz, CDCl3): δ = 166.7, 165.4, 144.2 (q, JCF = 106.8
Hz), 140.8, 131.0, 130.1, 129.4, 128.9, 127.1, 126.8 (q, JCF = 32.3
Hz), 126.5, 125.4 (q, JCF = 2.9 Hz), 124.3 (q, JCF = 272.3 Hz),
122.8, 121.5 (q, JCF = 4.7 Hz), 60.9, 32.0, 19.0, 14.4, 12.8.
13C NMR (75 MHz, CDCl3): δ = 165.7, 154.7, 154.1, 134.7 (q,
JCF = 3.5 Hz), 134.1, 124.9, 124.8 (q, JCF = 3.5 Hz), 121.6, 120.5,
95.4, 59.9, 24.3, 13.9.
MS (EI): m/z (%) = 454 (M+, 6), 382 (17), 381 (100).
HRMS: m/z calcd for C16H18F3IN2O2: 454.0365; found: 454.0387.
Anal. Calcd for C16H18F3IN2O2 (454.23): C, 42.31; H, 3.99; N, 6.17.
Found: C, 42.06; H, 3.77; N, 6.23.
MS (EI): m/z (%) = 387 (M+, 96), 386 (100), 359 (12), 358 (42), 342
(12), 314 (30), 299 (16), 298 (13).
Ethyl 8-Iodo-4-methyl-2-oxo-1,2-dihydro-6-quinolinecarboxy-
late (7a)
HRMS: m/z calcd for C22H20F3NO2: 387.1446; found: 387.1463.
A quantity of the crude product 6a (14.4 g, corresponding to 29.7
mmol, relative to the amount of starting meterial, assuming 100%
conversion) was dissolved in a solution of ZnCl2 (1.5 M, 99 mL,
149 mmol). The solvent was removed under reduced pressure and
the remaining mixture was taken up in EtOH (100 mL), and stirred
overnight at 80 °C. The mixture was then cooled to r.t. and 7a (7.18
g, 68%) precipitated as a white solid which was washed with a small
amount of EtOH; mp 224 °C.
Anal. Calcd for C22H20F3NO2 (387.39): C, 68.21; H, 5.20; N, 3.62.
Found: C, 68.42; H, 5.30; N, 3.44.
Ethyl 4-{[(E)-(Dimethylamino)methylidene]amino}-3-[(1Z)-3-
ethoxy-1-methyl-3-oxoprop-1-enyl]-5-iodobenzoate (6a)
To a solution of 5a (7.08 g, 15.0 mmol) in THF (7 mL) with tetrade-
cane (10 drops) as internal standard was added i-PrMgCl (0.94 M,
17.6 mL, 16.5 mmol) at –30 °C. The reaction mixture was stirred
for 15 min, then CuCN 2LiCl (1.0 M, 16.5 mL, 16.5 mmol) was
added followed by ethyl (Z)-3-iodobut-2-enoate (5.40 g, 22.5
mmol) and the mixture was warmed to r.t. After 45 min, the reaction
was quenched with aq sat. NH4Cl solution. The mixture was poured
into aq NH4Cl solution (200 mL) and extracted with EtOAc
(3 × 400 mL). The combined organic phases were washed with
brine (200 mL), dried (MgSO4), and concentrated. An aliquot was
removed from the crude product (2% of the crude product, deter-
mined by weighing, corresponding to 0.27 mmol) and purified by
flash chromatography (pentane–EtOAc, 88:12). The product 6a
(100 mg, 81%) was obtained as a yellow oil.
IR (KBr): 3435 (w), 1719 (w), 1675 (m), 1596 (w), 1271 (m), 762
(w) cm–1.
1H NMR (300 MHz, pyridine-d5): δ = 10.38 (s, 1 H, NH), 8.76 (d, 1
H, J = 1.8 Hz, ArH-7), 8.36 (d, 1 H, J = 1.8 Hz, ArH-5), 6.64 (s, 1
H, ArH-3), 4.39 (q, 2 H, J = 7.2 Hz, CO2CH2CH3), 2.27 (s, 3 H,
ArCH3), 1.28 (t, 3 H, J = 7.2 Hz, CO2CH2CH3).
13C NMR (75 MHz, pyridine-d5): δ = 164.8, 162.4, 148.6, 142.8,
141.2, 127.3, 125.6, 122.6, 120.9, 86.4, 61.6, 18.5, 14.4.
MS (EI): m/z (%) = 357 (M+, 100), 329 (23), 312 (85), 256 (9), 207
(25), 157 (15), 129 (20), 102 (13).
HRMS: m/z calcd for C13H12INO3: 356.9862; found: 356.9856.
IR (film): 3430 (w), 2980 (w), 1715 (m), 1643 (m), 1581 (m), 1369
(w), 1265 (m), 1104 (w), 768 (w) cm–1.
Anal. Calcd for C13H12INO3 (357.14): C, 43.72; H, 3.39; N, 3.92.
Found: C, 44.04; H, 3.20; N, 3.81.
Synthesis 2003, No. 2, 233–242 ISSN 0039-7881 © Thieme Stuttgart · New York

242
A. Staubitz et al.
PAPER
8-Iodo-4-methyl-6-(trifluoromethyl)-2(1H)-quinolinone (7b)
Compound 6b (1.35 g, 2.97 mmol) was dissolved in a solution of
ZnCl2 (1.15 M, 13 mL, 15.0 mmol). The solvent was removed un-
der reduced pressure and the remaining mixture was redissolved in
EtOH (10 mL), and stirred overnight at 80 °C. The mixture was then
cooled to r.t. and 7b (896 mg, 85%) precipitated as a white solid
which was washed with small amounts of EtOH. Flash chromatog-
raphy (pentane–EtOAc, 33:67) yielded an additional amount of 7b
(75 mg, 7%, total yield: 971 mg, 92%); mp 241 °C.
1H NMR (300 MHz, pyridine-d5): δ = 8.49 (d, 1 H, J = 1.6 Hz, ArH-
7), 8.38 (d, 1 H, J = 1.6 Hz, ArH-5), 7.77 (d, 2 H, J = 7.5 Hz, ArH
2′,6′), 7.55–7.54 (m, 1 H, ArH-4′), 7.38–7.31 (m, 2 H, ArH-3′,5′),
7.27–7.22 (m, 1 H, ArH-3), 6.67 (s, 1 H), 6.56 (s, 1 H), 4.36 (q, 2 H,
J = 7.1 Hz, CO2CH2CH3), 2.22 (d, 3 H, J = 1.3 Hz, ArCH3), 1.24 (t,
3 H, J = 7.1 Hz, CO2CH2CH3).
13C NMR (75 MHz, pyridine-d5): δ = 166.1, 161.7, 148.7, 143.9,
140.8, 130.4, 129.9, 129.0, 127.9, 126.7, 126.5, 123.7, 122.2, 121.0,
74.8, 61.2, 19.0, 14.4.
IR (KBr): 3436 (m), 3338 (s), 3057 (w), 1683 (vs), 1602 (s), 1440
(w), 1382 (m), 1369 (m), 1302 (vs), 1219 (m), 1153 (s), 1122 (s),
1099 (s), 1082 (m), 959 (w), 891 (m), 766 (m), 727 (w), 706 (w),
666 (m), 632 (m), 615 (m), 580 (w), 520 (m), 490 (w) cm–1.
1H NMR (300 MHz, pyridine-d5): δ = 8.38 (d, J = 1.8 Hz, 1 H, ArH-
7), 7.92–7.89 (m, 1 H, ArH-5), 6.70 (d, J = 1.3 Hz, 1 H, ArH-3),
2.29 (d, J = 1.3 Hz, 3 H, CH3).
MS (EI): m/z = (%) 337 (M+, 20), 336 (18), 335 (62), 334 (30), 322
(22), 321 (100), 320 (31), 319 (43), 318 (27), 306 (23), 292 (23),
291 (14), 290 (36), 276 (24), 262 (13), 248 (23), 217 (11), 105 (10),
77 (12).
HRMS: m/z calcd for C20H19NO4: 337.1314; found: 337.1331.
13C NMR (75 MHz, pyridine-d5): δ = 162.4, 148.3, 142.5, 136.8 (q,
JCF = 3.5 Hz), 124.3 (q, JCF = 32.9 Hz), 123.0, 122.8 (q, JCF = 3.5
Hz), 121.1, 113.4, 18.4.
References
(1) Joule, J. A.; Mills, K.; Smith, G. F. Heterocyclic Chemistry,
5th ed.; Blackwell Science: Oxford, 1998.
MS (EI): m/z (%) = 353 (M+, 100), 324 (38), 198 (16), 197 (19).
(2) (a) Rottländer, M.; Boymond, L.; Bérillon, L.; Leprêtre, A.;
Varchi, G.; Avolio, S.; Laaziri, H.; Quéguiner, G.; Ricci, A.;
Cahiez, G.; Knochel, P. Chem.–Eur. J. 2000, 6, 767.
(b) Jensen, A. E.; Dohle, W.; Sapountzis, I.; Lindsay, D. M.;
Vu, V. A.; Knochel, P. Synthesis 2002, 565.
HRMS: m/z calcd for C11H7F3INO: 352.9524; found: 352.9554.
Anal. Calcd for C11H7F3INO (353.08): C, 37.42; H, 2.00; N, 3.97.
Found: C, 37.34; H, 1.93; N, 3.92.
(3) Abarbri, M.; Thibonnet, J.; Bérillon, L.; Dehmel, F.;
Rottländer, M.; Knochel, P. J. Org. Chem. 2000, 65, 4618.
(4) (a) Lindsay, D. M.; Dohle, W.; Jensen, A. E.; Kopp, F.;
Knochel, P. Org. Lett. 2002, 4, 1819. (b) Sy, W.-W. Synth.
Commun. 1992, 22, 3215. (c) Toste, D.; McNulty, J.; Still, I.
W. J. Synth. Commun. 1994, 24, 1617. (d) McNulty, J.;
Still, I. W. J. Tetrahedron Lett. 1991, 32, 4875.
(5) Varchi, G.; Jensen, A. E.; Dohle, W.; Ricci, A.; Cahiez, G.;
Knochel, P. Synlett 2001, 477.
(6) Knochel, P.; Yeh, M. C. P.; Berk, S. C.; Talbert, J. J. Org.
Chem. 1988, 53, 2390.
(7) Piers, E.; Wong, T.; Coish, P. D.; Rogers, C. Can. J. Chem.
1994, 72, 1816.
Ethyl 8-[Hydroxy(phenyl)methyl]-4-methyl-2-oxo-1,2-dihydro-
6-quinolinecarboxylate (9)
Compound 7a (178 mg, 0.50 mmol) was suspended in anhyd THF
(1 mL) and cooled to –30 °C. PhMgCl (1.9 M, 0.29 mL, 0.55 mmol)
was added and the reaction mixture was stirred for 15 min, then i-
PrMgCl (0.94 M, 0.59 mL, 0.35 mmol) was added and the mixture
was stirred for a further 30 min. Benzaldehyde (159 mg, 1.5 mmol)
was then added and the incomplete reaction was was quenched after
2 h by the addition of aq sat. NH4Cl solution. The mixture was
poured into aq NH4Cl solution (50 mL), extracted with EtOAc
(3 × 200 mL), washed with brine (25 mL), dried (MgSO4) and con-
centrated. Purification by flash chromatography (pentane–EtOAc–
pyridine, 49:49:2) afforded 9 (169 mg, 58%) as a white solid; mp
237 °C.
(8) Knochel, P.; Singer, R. D. Chem. Rev. 1993, 93, 2117.
(9) Knochel, P.; Millot, N.; Rodriguez, A. L.; Tucker, C. A. Org.
React. 2001, 58, 417.
(10) Negishi, E. Acc. Chem. Res. 1982, 15, 340.
(11) Brown, D. J.; Waring, P. Aust. J. Chem. 1973, 26, 443.
IR (KBr): 3422 (m), 2981 (m), 1713 (s), 1660 (vs), 1603 (s), 1576
(m), 1453 (m), 1392 (m), 1365 (m), 1281 (s), 1212 (s), 1147 (s),
1025 (m), 975 (w), 913 (w), 864 (m), 767 (m), 705 (m), 611 (m),
500 (w) cm–1.
Synthesis 2003, No. 2, 233–242 ISSN 0039-7881 © Thieme Stuttgart · New York