Synthesis of 3-substituted quinolines via transition-metal-catalyzed reductive cyclization of o-nitro baylis-hillman acetates

Article abstract of DOI:10.1021/jo034447c

Reductive cyclization of o-nitro-substituted Baylis-Hillman acetates by carbon monoxide, catalyzed by [Cp*Fe(CO)₂]₂, gives moderate to good yields of 3-substituted quinolines.

Full text of DOI:10.1021/jo034447c

to the intramolecular reaction of o-nitroarenes bearing
pendant unsaturation as an entry to important nitrogen
heterocycles.5
Syn th esis of 3-Su bstitu ted Qu in olin es via
Tr a n sition -Meta l-Ca ta lyzed Red u ctive
Cycliza tion of o-Nitr o Ba ylis-Hillm a n
Aceta tes
The Baylis-Hillman reaction is a powerful carbon-
carbon bond-forming reaction between a carbonyl com-
pound and an electrophilic olefin.6 The products of these
reactions, the so-called Baylis-Hillman adducts (BH
adducts), are polyfunctional allylic alcohols. Several
groups have targeted BH adducts as precursors to
nitrogen heterocycles to give quinolines,7 dihydroquino-
lines,8 2-quinolones,9 4-quinolones,10 and quinoline N-
oxides.11 These reactions, however, often give mixtures
of products,9c require substrates that are not easily
prepared,7a or lack generality.7b,c,8
David K. O’Dell and Kenneth M. Nicholas*
Department of Chemistry and Biochemistry, University of
Oklahoma, 620 Parrington Oval, Norman, Oklahoma 73019
knicholas@ou.edu
Received April 8, 2003
Recently we reported the Fp2-catalyzed cyclization of
o-nitro-substituted BH adducts 1 which produced, quite
surprisingly, indoles and N-formylindolines, albeit in low
yield (eq 1a).12
Abstr a ct: Reductive cyclization of o-nitro-substituted Bay-
lis-Hillman acetates by carbon monoxide, catalyzed by
[Cp*Fe(CO)2]2, gives moderate to good yields of 3-substituted
quinolines.
Quinolines are important heterocyclic compounds that
are used for a variety of applications from pharmaceu-
ticals to materials.1 While numerous quinoline syntheses
have been developed,2 many suffer from limitations
(harsh conditions, poor availability of starting materials,
limited regioselectivity) that preclude their general ap-
plication. These factors have spurred the development
of new synthetic methods for these important com-
pounds.3
A recent focus of the research in our laboratory has
been the discovery and development of transition-metal-
promoted amination reactions of hydrocarbons.4 After
uncovering the intermolecular [CpFe(CO)2]2 (Fp2)-cata-
lyzed allylic amination of olefins by nitrobenzene and
CO,4f we have examined the application of this protocol
Bassaviah et al. found that the reduction of o-nitro-
substituted Baylis-Hillman acetates (BH acetates) by Fe/
AcOH gives 2-quinolones.9b Given the markedly different
outcome of the cyclization of BH adducts with the [CpFe-
(CO)2]2/CO reductive system compared to that of other
methods, we chose to investigate the reductive behavior
of the corresponding BH acetates.
The BH adducts 1a -f were efficiently acetylated by
13
treatment with either AcCl/pyridine or Ac2O/H2SO4 to
give the BH acetates 2a -f in 71-99% yield (eq 2).
(1) Balasubramanian, M.; Keay, J . G. In Comprehensive Heterocyclic
Chemistry II; Katritzky, A. R., Rees, C. W., Scriven, E. F. V., Eds.;
Pergamon: Oxford, 1996; Vol. 5, Chapter 5.06, p 245.
(2) (a) J ones, G. In Comprehensive Heterocyclic Chemistry II;
Katritzky, A. R., Rees, C. W., Scriven, E. F. V., Eds.; Pergamon:
Oxford, 1996; Vol. 5, Chapter 5.05, p 245. (b) J ones, G. In The
Chemistry of Heterocyclic Compounds; Weissberger, A., Taylor, A. C.,
Eds.; Wiley: New York, 1977; Vol. 32, Chapter 2, p 93.
(3) (a) J iang, B.; Si, Y.-G. J . Org. Chem. 2002, 67, 9449. (b) Lee, B.
S.; Lee, J . H.; Chi, D. Y. J . Org. Chem. 2002, 67, 7884. (c) Syeda Huma,
S. H. Z.; Halder, R.; Singh Kalra, S. S.; Das, J .; Iqbal, J . Tetrahedron
Lett. 2002, 43, 6485. (d) Ranu, B. C.; Hajra, A.; J ana, U. Tetrahedron
Lett. 2000, 41, 531. (e) Cho, C. S.; Oh, B. H.; Shim, S. C. Tetrahedron
Lett. 1999, 40, 1499. (f) Cacchi, S.; Fabrizi, G.; Marinelli, F. Synlett
1999, 401. (g) Suginome, M.; Fukuda, T.; Ito, Y. Org. Lett. 1999, 1,
1977. (h) Katritzky, A. R.; Arend, M. J . Org. Chem. 1998, 63, 9989. (i)
Wrobel, Z. Tetrahedron 1998, 54, 2607. (j) Zhou, L.; Zhang, Y. J . Chem.
Soc., Perkin Trans. 1 1998, 2899. (k) Kusuma, H.; Yamashita, Y.;
Uchiyama, K.; Narasaka, K. Bull. Chem. Soc. J pn. 1997, 70, 965. (l)
Mahanty, J . S.; De, M.; Das, P.; Kundu, N. G. Tetrahedron 1997, 53,
13397. (m) Ruhland, T.; Kunzer, H. Tetrahedron Lett. 1996, 37, 2757
and references therein.
(4) (a) Penoni, A.; Nicholas, K. M. J . Chem. Soc., Chem. Commun.
2002, 484. (b) Penoni, A.; Volkmann, J .; Nicholas, K. M. Org. Lett. 2002,
4, 699. (c) Srivastava, R. S.; Kolel-Veetil, M.; Nicholas, K. M..
Tetrahedron Lett. 2002, 43, 931. (d) Singh, S.; Nicholas, K. M Synth.
Commun. 2001, 31, 3087. (e) Kolel-Veetil, M. K.; Khan, M. A.; Nicholas,
K. M. Organometallics 2000, 19, 3754. (f) Srivastava, R. S.; Nicholas,
K. M. J . Chem. Soc., Chem. Commun. 1998, 24, 2705. (g) Srivastava,
R. S.; Nicholas, K. M. J . Am. Chem. Soc. 1997, 119, 3302. (h)
Srivastava, R. S.; Nicholas, K. M. Tetrahedron Lett. 1994, 35, 8739.
(i) Srivastava, R. S.; Nicholas, K. M. J . Org. Chem. 1994, 59, 5365. (j)
Srivastava, A.; Ma, Y.; Pankayatselvan, R.; Dinges, W.; Nicholas, K.
M. J . Chem. Soc., Chem. Commun. 1992, 11, 853.
The initial reaction of acetate 2a (Zn ) H, RdCO2Me)
employing Fp2 as a catalyst under 55 atm of CO in
dioxane (150 °C, 21 h) afforded a 21% isolated yield of
(5) Transition-metal-catalyzed reductive cyclization of ortho-substi-
tuted nitroaromatics is a useful route to several heterocyclic systems.
(a) Catalytic Reductive Carbonylation of Organic Nitro Compounds;
Cenini, S., Ragaini, F., Eds.; Kluwer: Dordrecht, The Netherlands,
1996. (b) Soderberg, B. C.; Wallace, J . M.; Tamariz, J . Org. Lett. 2002,
4, 1339. (c) Aoyagi, Y.; Mizusaki, T.; Ohta, A. Tetrahedron Lett. 1996,
37, 9203. (d) Akazome, M.; Kondo, T.; Watanabe, Y. J . Org. Chem.
1994, 59, 3375 and references therein.
(6) (a) Ciganek, E. Org. React. 1997, 51, 201. (b) Basavaiah, D.; Rao,
P. D.; Hyma, R. S. Tetrahedron 1996, 52, 8001. (c) Drewes, S. E.; Roos,
G. H. P. Tetrahedron 1988, 44, 4653.
(7) (a) Chung, Y. M.; Lee, H. J .; Hwang, S. S.; Kim, J . N. Bull.
Korean Chem. Soc. 2001, 22, 799. (b) Kim, J . N.; Lee, H. J .; Lee, K. Y.;
Kim, S. K. Tetrahedron Lett. 2001, 42, 3737. (c) Kim, J . K.; Chung, Y.
M.; Im, Y. J . Tetrahedron Lett. 2002, 43, 6209.
(8) Kim, J . N.; Kim, H. S.; Gong, H. G.; Chung, Y. M. Tetrahedron
Lett. 2001, 42, 8341.
10.1021/jo034447c CCC: $25.00 © 2003 American Chemical Society
Published on Web 07/09/2003
J . Org. Chem. 2003, 68, 6427-6430
6427

TABLE 1. Op tim iza tion of th e Con ver sion of Aceta te 2a to Qu in olin e 3a
amt of
2a a
(mmol)
catalystb/
concn
(mol %)
CO pressure
(atm)
time
(h)
yield of
conversnd
(%)
entry
3a c (%)
1
2
3
1.16
1.0
0.11
Fp2/25
Fp2/100
Fp2/35
56
56
56
21
21
23
45
46
46
44
42
42
42
70
70
42
21
26
21
69
83
37
24
80
79
73
28
41
67
ND
>99
46
>99
>99
>99
>99
>99
>99
>99
4
5
6
7
8
0.11
0.11
0.11
0.11
0.11
0.11
0.11
0.11
0.72
[Cp*Ru(CO)2]2/35
[(C5H3)2(SiMe2)2}Ru2(CO)4/35
(Cp)2Fe2(CO)2(dppe)/20
Fp*2/5
Fp*2/10
Fp*2/10
Fp2/20
[Cp*Ru(CO)2]2/20
Fp*2/10
56
56
20
56
20
6
6
6
6
9
10
11
12
>99
a
b
0.02 M in dioxane, T ) 150 °C. Fp2 ) [CpFe(CO)2]2; Fp*2 ) [Cp*Fe(CO)2]2. c Entries 1 and 12 are isolated yields; entries 2-11 are
d
GC yields using naphthalene as an internal standard. The percent conversion of 2a was determined by GC with naphthalene as an
internal standard.
the quinoline 3a as the major product (eq 1b, Table 1,
entry 1). It is worth noting that none of the previously
encountered indole or N-formylindoline was detected
(NMR/GC-MS of crude reaction mixtures).
a Gould-J acobs reaction, followed by chlorination, and
then catalytic reduction with H2/Ni or Pd catalysts.15
More recent reports have employed sulfonamides derived
from BH adducts that undergo intramolecular aromatic
substitution via the pendant amino group.7 The nitro BH
acetates required for our route are easily prepared in high
yield, and the reaction’s tolerance for electronically
diverse substituents on the aromatic ring promises to
make this a general and preferred route to these quino-
lines.
The reaction was then optimized with respect to
substrate concentration, catalyst, catalyst loading, and
CO pressure (Table 1, entries 2-11). Initial success with
the Fp2 complex prompted us to study other group 8
metal carbonyl dimers as potential catalysts for this
reaction. Commercially available [Cp*Fe(CO)2]2 (Fp*2)
was found to be a superior catalyst, giving good yields
at low catalyst loading (entry 7) and at lower CO pressure
(entries 9 and 12). The conditions in entries 9 and 12 were
chosen as the most convenient since the lower pressure
enables the reactions to be safely carried out in common
thick-walled glass vessels.14
After the initial optimization with substrate 2a , the
BH acetates 2b-f were cyclized employing similar condi-
tions, the results of which are presented in Table 2. The
reaction is effective for substrates bearing either electron-
donating (entries 1 and 3) or electron-withdrawing groups
(entry 2), though the former react more slowly. The
carbomethoxy and cyano groups are both tolerated well
(entry 5). The benzo[h]quinoline 3e was also accessible
(entry 4). In addition to quinolines 3b-f some minor
products (inseparable) were also isolated. GC-MS analy-
sis revealed two main byproducts 2 and 4 mass units
higher than the quinoline with fragmentation patterns
similar to those of the quinolines, suggestive of the
corresponding dihydro- and tetrahydroquinolines.
The most established route to 3-carboalkoxyquinolines
requires the preparation of 4-quinolone derivatives through
The mechanistic pathway for the Fp*2-catalyzed reduc-
tive cyclization to quinolines is presently uncertain. Our
prior probes of the corresponding intermolecular allylic
aminations have excluded free nitrosoarene and nitrene
intermediates4f and suggested a role for coordinated
organonitrogen species.4e Furthermore, the contrasting
2-quinolone products formed in reactions of BH acetates
2 with conventional metal reductants (presumably via
hydroxylamine or amine addition to the carboxylate
group)9b appear to exclude these intermediates as well
in the iron-promoted reactions. Besides Fp*-catalyzed
reduction of the nitro group, a coordinated organonitro-
gen and/or olefin(allyl) species may thus be involved in
the cyclization (and subsequent reduction) step(s). The
marked difference in reaction products derived from the
BH alcohols (indoles, N-formylindolines) as compared to
the BH acetates (quinolines) is also striking. We sug-
gested that the formation of indole and N-formylindoline
in the former occurred via a retroaldol reaction of a
cyclized â-hydroxy ester intermediate.12 The suppressed
decarbonylation pathway found with the BH acetates
may reflect the inhibited retroaldol reaction of the
corresponding â-acetoxy ester intermediates. Efforts are
currently under way to further elucidate the mechanistic
details and to expand the scope of these novel metal-
catalyzed reductive cyclizations.
(9) (a) Lee, K. Y.; Kim, J . N. Bull. Korean Chem. Soc. 2002, 23, 939.
(b) Basavaiah, D.; Reddy, R. M.; Kumaragurubaran, N.; Sharada, D.
S. Tetrahedron 2002, 58, 3693. (c) Familoni, O. B.; Kaye, P. T.; Klaas,
P. J . J . Chem. Soc., Chem. Commun. 1998, 24, 2563.
(10) Chung, Y. M.; Lee, H. J .; Hwang, S. S.; Kim, J . N. Bull. Korean
Chem. Soc. 2001, 22, 135.
Exp er im en ta l Section
(11) Kim, J . N.; Lee, K. Y.; Kim, H. S.; Kim, T. Y. Org. Lett. 2000,
2, 343.
Gen er al Meth ods. Compounds 2a,13 [Cp*Ru(CO)2]2,16 [(C5H3)2-
(SiMe2)2]Ru2(CO)4,17 Cp2Fe2(CO)2(dppe),18 and [Cp*Fe(CO)2]2
19
(12) Nicholas, K. M.; O’Dell, D. K. Tetrahedron 2003, 59, 747.
(13) Mason, P. L. H.; Emslie, N. D. Tetrahedron 1994, 50, 12001.
(14) E.g., Fisher-Porter bottles can be obtained from Andrews Glass
Co. A head for the introduction of gaseous reactants has been described
by L. Messerle: ACS Symp. Ser. 1987, 357 (Experimental Organome-
tallic Chemistry), 198-203.
were prepared according to literature procedures and gave
(15) Ohnmacht, C. J .; Davis, F.; Lutz, R. E. J . Med. Chem. 1971,
14, 17.
6428 J . Org. Chem., Vol. 68, No. 16, 2003

TABLE 2. Qu in olin es Syn th esized by [Cp *F e(CO)2]2-Ca ta lyzed Cycliza tion of BH Aceta tes
a
Isolated yield after chromatography/recrystallization.
1
satisfactory spectroscopic data. H NMR spectra were obtained
at 300 MHz and 13C NMR spectra at 75.45 MHz. Flash
chromatography was carried out using silica gel with the
indicated eluants.
1753, 1706, 1521, 1204, 1027 cm-1; 1H NMR (d6-acetone) δ 2.14
(s, 3H), 3.74 (s, 3 H), 3.74 (s, 3 H), 5.74 (d, J ) 1.2 Hz, 1 H), 6.43
(d, J ) 0.3 Hz, 1 H), 7.21 (d, J ) 0.3 Hz, 1 H), 7.67-7.71 (m, 2
H), 8.12 (td, J ) 9.0 Hz, J ) 1.5 Hz, 1H); 13C NMR (75.45 MHz;
d6-acetone) δ 20.6, 52.5, 68.7, 127.5, 128.5, 129.4, 130.3, 135.7,
138.8, 140.0, 165.2, 169.4; MS (ESI) m/z 336 (M + Na, 100). Anal.
Calcd for C13H12NO6Cl: C, 49.78; H, 3.86; N, 4.47. Found: C,
49.85; H, 3.89; N, 4.46.
P r ep a r a tion of Ba ylis-Hillm a n Aceta tes 2b-f. The fol-
lowing procedure is representative of the preparation of 2b-f.
The Baylis-Hillman adduct 1b (500 mg, 1.78 mmol) was
dissolved in CH2Cl2 (15 mL) and cooled with an ice bath.
Pyridine (0.29 mL, 3.56 mmol) was added followed by acetyl
chloride (0.26 mL, 3.56 mmol) and the mixture stirred for 1 h.
The reaction mixture was then taken up with ether and washed
with 2 M HCl (2 × 20 mL), saturated NaHCO3 (2 × 20 mL),
and H2O (1 × 10 mL). The organic layer was dried with MgSO4
and concentrated to give the acetates generally as white solids,
which were obtained in pure form by recrystallization from
toluene or by silica gel chromatography with 1:1 hexane/ether.
Da ta for m eth yl 2-[a cetyloxym eth yl(6-n itr o-1,3-ben zo-
d ioxol-5-yl)]a cr yla te (2b): 94% yield; mp 123-125 °C; IR (KBr)
1753, 1714, 1521, 1220, 1035 cm-1; 1H NMR (CD3CN) δ 2.07 (s,
3 H), 3.72 (s, 3 H), 5.58 (d, J ) 1.2 Hz, 1 H), 6.14 (d, J ) 0.9 Hz,
1 H), 6.15 (d, J ) 0.9 Hz, 1 H), 7.04 (s, 1 H), 7.12 (d, J ) 1.2 Hz,
1 H), 7.55 (s, 1 H); 13C NMR (CD3CN) δ 21.2, 52.9, 69.5, 104.9,
106.2, 108.1, 123.1, 128.5, 130.6, 139.5, 153.5, 166.0, 170.2; MS
(ESI) m/z 346.1 (M + Na, 63). Anal. Calcd for C14H13NO8: C,
52.02; H, 4.05; N, 4.33. Found: C, 51.92; H, 4.07; N, 4.30.
Da ta for m eth yl 2-[a cetyloxym eth yl(5-ch lor o-2-n itr o-
p h en yl)]a cr yla te (2c): 99% yield; mp 103-104 °C; IR (KBr)
Da ta for m eth yl 2-[a cetyloxym eth yl(4,5-d im eth oxy-2-
n it r op h en yl)]a cr yla t e (2d ): 96% yield; mp 145-147 °C; IR
1
(KBr) 1753, 1719, 1523 cm-1; H NMR (d6-acetone) δ 2.10 (s, 3
H), 3.75 (s, 3 H), 3.95 (s, 3 H), 3.96 (s, 3 H), 5.58 (d, J ) 1.2 Hz,
1 H), 6.35 (s, 1 H), 7.10 (s, 1H), 7.27 (d, J ) 1.2 Hz, 1 H), 7.68
(s, 1 H); 13C NMR (75.45 MHz; d6-acetone) δ 21.0, 52.7, 56.8,
56.9, 69.6, 109.1, 110.9, 128.4, 128.6, 140.1, 149.7, 154.7, 165.9,
169.7; HRMS (ESI) m/z calcd for C15H17NO8Na (M + Na)
362.0852, found 362.0816.
Da ta for m eth yl 2-[a cetyloxym eth yl(1-n itr o-2-n a p h th -
yl)]a cr yla te (2e): 93% yield; mp 105-107 °C; IR (KBr) 1753,
1707, 1529 cm-1; 1H NMR (d6-acetone) δ 2.12 (s, 3 H), 3.72 (s, 3
H), 5.89 (d, J ) 1.5 Hz, 1 H); 6.50 (d, J ) 0.9 Hz, 1 H); 6.90 (s,
1 H), 7.68 (d, J ) 9.0 Hz, 1 H), 7.71-7.81 (m, 3 H), 8.13 (m, 1
H), 8.23 (d, J ) 9.0 Hz, 1 H); 13C NMR (75.45 MHz; d6-acetone)
δ 21.4, 53.3, 70.3, 123.1, 125.6, 126.1, 128.6, 129.4, 129.7, 129.9,
130.8, 132.9, 135.3, 139.6, 166.1, 170.1; HRMS (ESI) m/z calcd
for C17H15NO6Na (M + Na) 352.0797, found 352.0558.
Da ta for 2-[a cetyloxym eth yl(2-n itr op h en yl)a cr ylon itr ile
(2f): 71% yield; yellow oil; Rf ) 0.25; IR (KBr) 2228, 1750, 1528
1
cm-1; H NMR (d6-acetone) δ 2.18 (s, 3 H), 6.24 (d, J ) 0.9 Hz,
(16) King, R. B.; Iqbal, M. Z.; King, A. D., J r. J . Organomet. Chem.
1979, 171, 53.
(17) Ovchinnikov, M. V.; Angelici, R. J . J . Am. Chem. Soc. 2000,
122, 6130.
(18) Haines, R. J .; Du Preez, A. L. J . Organomet. Chem. 1970, 21,
181.
(19) Astruc, D.; Catheline, D. Organometallics 1984, 3, 1094.
1 H), 6.36 (s, 1 H), 6.98 (s, 1 H), 7.65-7.72 (m, 1 H), 7.82-7.89
(m, 2 H), 8.11 (d, J ) 7.8 Hz); 13C NMR (75.45 MHz; d6-acetone)
δ 20.5, 70.2, 116.6, 121.5, 125.5, 129.1, 130.7, 131,8, 134.7, 135.3,
148.5, 169.2; HRMS (ESI) m/z calcd for C12H10N2O4Na (M + Na)
269.0538, found 269.0490.
J . Org. Chem, Vol. 68, No. 16, 2003 6429

P r ep a r a tion of 3-Su bstitu ted Qu in olin es by Ir on -Ca ta -
lyzed Red u ctive Cycliza tion . Meth ylqu in olin e-3-ca r boxy-
la te (3a ). In a glass-lined, stainless steel Parr reactor or a thick-
walled glass vessel (e.g., Fisher-Porter bottle14) the acetate 3a
(200 mg, 0.72 mmol) was combined with [Cp*Fe(CO)2]2 (35 mg,
0.070 mmol) and dioxane (70 mL). The vessel was flushed three
times with CO (fume hood!), charged to 100 psi (6 atm; ca. 15
equiv) with CO, and heated to 150 °C with an oil bath for 41 h.
After cooling, the vessel was vented (fume hood!), and the ruby-
colored solution was concentrated on a rotary evaporator. The
solid red-brown residue was chromatographed on SiO2 with
Et2O/hexanes (2:3) to give 134 mg (67%) of a white solid, which
was the quinoline 3a , Rf ) 0.35 (1:1, Et2O/hexanes), spectro-
scopically identical to that reported previously:20 mp 68-71 °C;
lit.21 mp 70-74 °C. A portion of the catalyst [Cp*Fe(CO)2]2 was
also recovered (13 mg, 0.030 mmol).
Rf ) 0.44); 60% yield; mp 161-163 °C; IR (KBr) 1722, 1618,
1599, 1505, 1432 cm-1 1H NMR (300 MHz; d6-acetone) δ 3.95
;
(s, 3 H), 4.0 (s, 3 H), 4.04 (s, 3 H), 7.43 (s, 1 H), 7.45 (s, 1 H),
8.70 (s, 1 H), 9.14 (s, 1 H); 13C NMR (75.45 MHz; d6-acetone) δ
51.9, 55.7, 55.8, 106.5, 107.9, 121.3, 122.7, 136.1, 147.5, 147.8,
150.9, 154.9, 165.9; HRMS (ESI) m/z calcd for C13H14NO4 (M +
H) 248.0923, found 248.0795 (100); calcd for C13H13NO4Na (M
+ Na) 270.0742, found 270.0569 (44).
Da ta for m eth yl ben zo[h ]qu in olin e-3-ca r boxyla te (3e):
40 h reaction; chromatography with Et2O/hexanes (3:7; Rf
)
0.32); 47% yield; mp 125-127 °C; IR (KBr) 3066, 2949, 1706,
1
1610, 1323, 1267, 1214 cm-1; H NMR (d6-acetone) δ 4.01 (s, 3
H), 7.76-7.86 (m, 2 H), 7.93-8.1 (m, 3 H), 8.90 (d, J ) 2.1 Hz,
1 H), 9.26-9.34 (m, 1 H), 9.45 (d, J ) 2.1 Hz, 1 H); 13C NMR
(d6-acetone) δ 53.5, 125.4, 126.4, 126.8, 127.3, 128.9, 129.6, 130.1,
130.9, 132.4, 136.2, 138.0, 150.0, 150.1, 166.8; MS (EI) m/z 237
(M+, 100), 206 (60), 178 (65), 151 (25). Anal. Calcd for C15H11
-
Da ta for m eth yl [1,3]d ioxolo[4,5-g]qu in olin e-7-ca r boxy-
la te (3b): 80 h reaction time; chromatography with CHCl3/
MeOH (30:1; Rf ) 0.44); 65% yield; white needles; mp 210-213
NO2: C, 75.94; H, 4.67; N, 5.90. Found: C, 76.20; H, 4.75; N,
5.95.
°C; IR (KBr) 1709, 1470, 1203 cm-1 1H NMR (300 MHz; d6-
;
Da ta for qu in olin e-3-ca r bon itr ile (3f): 39 h; chromatog-
raphy with Et2O/hexanes (4:7; Rf ) 0.32); 65% yield; mp 104-
acetone) δ 3.95 (s, 3 H), 6.27 (s, 1 H), 7.36 (s, 1 H), 7.42 (s, 1 H),
8.71 (d, J ) 2.1 Hz, 1 H), 9.12 (d, J ) 2.1 Hz, 1 H); 13C NMR
(75.45 MHz; d6-acetone) δ 53.3, 104.3, 105.2, 106.9, 138.1, 149.1,
167.1; MS (EI) m/z 231 (M+, 100), 200 (95), 172 (65), 142 (15),
114 (20). Anal. Calcd for C12H9NO4: C, 62.33; H, 3.92; N, 6.05.
Found: C, 62.42; H, 3.94; N, 6.08.
Da ta for m eth yl 6-ch lor oqu in olin e-3-ca r boxyla te (3c):
24.5 h reaction; chromatography with CHCl3/MeOH (30:1; Rf )
0.78); 48% yield; mp 174-176 °C; IR (KBr) 3066, 2950, 1722,
1491, 1436, 1336, 1267, 1097, 819 cm-1; 1H NMR (d6-acetone) δ
4.00 (s, 3 H), 7.89 (dd, J ) 9.0 Hz, J ) 2.4 Hz, 1 H), 8.12 (d, J
) 9.0 Hz, 1 H), 8.24 (d, J ) 2.1 Hz, 1 H), 8.93 (d, J ) 1.5 Hz, 1
H), 9.35 (d, J ) 2.1 Hz, 1 H); 13C NMR (CDCl3) δ 52.7, 132.7,
127.5, 130.9, 132.7, 133.3, 137.7, 148.0, 150.0, 165.3; MS (EI)
m/z 221 (M+, 100), 190 (95), 162 (70), 127 (27), 99 (16), 74 (5);
HRMS (ESI) m/z calcd for C11H8ClNO2Na (M + Na) 244.0141,
found 244.0092.
106 °C; lit.21 mp 107-108 °C; IR (KBr) 2228, 1619, 1489 cm-1
;
1H NMR (d6-acetone) δ 7.77 (t, J ) 7.5 Hz, 1 H), 7.97 (t, J ) 7.5
Hz, 8.08-8.15 (m, 2 H), 8.90 (d, J ) 1.5 Hz, 1 H), 9.10 (d, J )
1.5 Hz, 1 H); 13C NMR (d6-acetone) δ 107.2, 117.7, 126.9, 129.0,
129.3, 130.1, 133.3, 142.5, 149.3, 150.5; MS (EI) m/z 154 (M+,
100), 127 (20), 100 (5).
Ack n ow led gm en t. We thank the NSF and Univer-
sity of Oklahoma (OU Graduate Alumni Fellowship to
D.K.O.) for financial support. We also appreciate the
technical assistance of J oe Wilkerson, Nicholas Black-
man, and Dr. Qaincai Liu.
Su p p or tin g In for m a tion Ava ila ble: Experimental pro-
cedures for the preparation of compounds 1a -f and their
characterizational data. This material is available free of
charge via the Internet at http://pubs.acs.org.
Da ta for m eth yl 6,7-d im eth oxyqu in olin e-3-ca r boxyla te
(3d ): 89 h reaction; chromatography with CHCl3/MeOH (30:1;
J O034447C
(20) Cain, M.; Weber, R W.; Guzman, F.; Cook, J . M.; Barker, S. A.;
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(21) Gilman, H.; Spatz, S. M. J . Am. Chem. Soc. 1941, 63, 1556.
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