Carbene induced rearrangement products from two furoquinolinone scaffolds

Article abstract of DOI:10.1002/jhet.463

(Chemical Equation Presented) Novel double CH-insertion and rearrangement products (5, 6, and 7) were isolated from treatment of 1 or 2 with dimethyl diazomalonate (3) under dirhodiumtetrakis mediated carbenoid chemistry conditions. A new possible reaction pathway is suggested and discussed. Also other diazo compounds were tested.

Full text of DOI:10.1002/jhet.463

998
Carbene Induced Rearrangement Products from Two
Furoquinolinone Scaffolds
Vol 47
Karl-Fredrik Lindahl,* Anthony Carroll, Ronald J. Quinn, and Justin A. Ripper
Eskitis Institute, Griffith University, Brisbane, Queensland 4111, Australia
*E-mail: f.lindahl@imb.uq.edu.au or kflindahl@hotmail.com
Received November 17, 2009
DOI 10.1002/jhet.463
Published online 17 June 2010 in Wiley InterScience (www.interscience.wiley.com).
Novel double CH-insertion and rearrangement products (5, 6, and 7) were isolated from treatment of
1 or 2 with dimethyl diazomalonate (3) under dirhodiumtetrakis mediated carbenoid chemistry condi-
tions. A new possible reaction pathway is suggested and discussed. Also other diazo compounds were
tested.
J. Heterocyclic Chem., 47, 998 (2010).
INTRODUCTION
simple furans [7], benzofurans [8], and tris-2-furylme-
thane derivatives [9].
Furoquinolinones belong to a class of molecules exhib-
iting a wide variety of biological activities, including
antifungal, antibacterial, antiviral (HIV), antimicrobial,
antimalarial, insecticidal, antineoplastic, antidiuretic,
antiarrhythmic, and sedative properties [1,2]. Examples
of natural alkaloids containing the furoquinolinone core
structure include oligophyline [3], araliopsine [4], and
almeine [5] (Fig. 1).
RESULTS AND DISCUSSION
We wish to report unexpected results from metal car-
benoid-mediated chemistry using two analogues, 1 and
2, as substrates and dimethyl diazomalonate (3) as the
carbene precursor (Fig. 2). We have previously reported
a novel synthesis of the common furoquinolinone core
structure (1), describing the use of a palladium mediated
intramolecular Heck coupling as a key step [10] and an
alternative route to literature precedents [11]. The sec-
ond core structure 2 was synthesized through modifica-
tion of that protocol by using SEM in place of a methyl
substituent as protecting group to facilitate formation of
intermediate 9. Treatment of 9 with dry HCl yielded the
unprotected core structure 4, which could easily be con-
verted to the corresponding imine form 2 by further
treatment with POCl3 and sodium methoxide in two sep-
arate steps (Scheme 1). The carbene precursor 3 was
synthesised by known methods [12].
These naturally occurring alkaloids, and others
belonging to the furoquinolinone class of molecules, are
obvious derivatives of a common core structural unit 1,
having a double bond in the C ring. Structure 1 is there-
fore a good choice for functionalization to important
synthons for natural product synthesis and medicinal
chemistry applications. To our knowledge, this poten-
tially reactive core structure has not yet been exploited
in synthesis.
It was envisaged that an electrophilic metal carbenoid,
which is readily generated by metal catalyzed decompo-
sition of a diazo reagent [6], could be used to probe
reactivity of the C ring double bond of the furoquinoli-
none core structure. Previous studies on related struc-
tures have used metal carbenoid chemistry, such as
All reactions were carried out in dichloromethane,
with 2 mol % dirhodiumtetraacetate as catalyst and
C
V
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Carbene Induced Rearrangement Products from Two Furoquinolinone Scaffolds
999
Figure 1. Natural alkaloids with furoquinolinone core structure.
substrate 1 serving as a template for optimizing the
reaction conditions. Treating 1 with 3 using previous
reported literature procedures [8] with the aim of instal-
ling a cyclopropane functionality, did not consume start-
ing material (1) in all cases (<5%). Optimized reaction
conditions were found using 3.2 eq of 3 (Experimental),
leading to 100% consumption of 1 and formation of
furo products. Strikingly, the major product was the
double CH-insertion product 5, and the minor product
was a cyclopropanated double CH-insertion product 6
(Scheme 2).
Figure 2. Starting materials (1 and 2) and carbene precursor (3).
products 5 and 7. Interestingly, when reacting 2 with 3,
only the pyrano structure 7 was produced.
These quite different outcomes are most likely due to
two different initial reaction intermediates/transition
states A and A’ forming from 1 and 2, respectively, as
substrates (Scheme 4). Possibly substrate 1 reacts with 3
in the C-3 position first, while substrate 2 reacts with 3
in the C-2 position. This suggests that intermediate A is
formed and is sufficiently stable to undergo a second
addition to form transition state B, followed by ring
opening/ring closing to form 5 (Scheme 5).
In contrast, transition state A’ cannot undergo such
addition and is further stabilized by ring opening/rear-
rangement to give product 7 (Scheme 6). The ring clos-
ing pathway to form 7 proceeds most likely in a similar
fashion as suggested for product 5. These two early
reaction intermediates/transition states (A and A’) can
explain the two different outcomes observed and, ulti-
mately, this reflects the inherent electronic differences
However, treatment of the analogue substrate 2 with
3, under the same optimized conditions used as above,
gave only the unsaturated product 7 (Scheme 3). Two
aliquots of the carbene species must have reacted with
one substrate giving two CH-insertions on the one scaf-
fold, followed by ring opening of the furan ring, rear-
rangement and ring closure to give 5. Due to the excess
of the metal carbenoid present in the reaction mixture,
product 5 can also react further to the minor product 6.
Opening of the furan ring has been noticed before for
related structures under similar reaction conditions
[7(d),13] This is similar here, indicated by the presence
of the quarternary carbon at the C-2 position in both
Scheme 1
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K.-F. Lindahl, A. Carroll, R. J. Quinn, and J. A. Ripper
Vol 47
Scheme 2
of 1 and 2. Interestingly, it was noted product 7 does
not react further in the presence of excess of 3.
tively, a direct rhodium mediated opening of the furan
ring between the oxygen and C1 occurs [7(b),15]. Fur-
ther, the expected cyclopropanated products 9 and 10
were obtained from treatment of 1 and 2 with ethyl 2-
diazopropionate, however, no reaction was observed
when using 2-diazopropane as the carbene precursor.
Most interestingly products 5, 6, and 7 are, to our
knowledge, unprecedented rearrangement products.
Thus, for product 5 (and 6), this suggests a new reaction
pathway is taking place and might serve as a useful
application in related areas.
When changing dimethyl diazomalonate (3) for ethyl
2-diazopropionate (8) and optimizing the reaction proto-
col (Experimental), reaction of either 2 or 3 with 8 [14]
gave the expected cyclopropanated outcomes 9 and 10
in isolated yields of 43 and 69%, respectively
(Scheme 7). No ring opened product was observed in
either case. Treatment of either 2 or 3 with the less
stabilized carbene precursor 2-diazopropane under a
range of conditions, including with/without catalyst and/
or lowered/elevated temperatures, starting material was
recovered quantitatively in all attempts.
EXPERIMENTAL
In summary, three novel rearrangement products (5,
6, and 7) can be derived from two relatively similar sub-
strates 1 and 2, both belonging to the furoquionolinone
class of molecules. The outcomes can be explained by
different initial reaction intermediates/transition states,
such as A, B, and A’, due to inherently different elec-
tronic properties of 1 and 2. Thus, changing the rela-
tively remote functionality from an amide to an imine
(1 to 2) determines the reaction under the carbene chem-
istry conditions. Other reaction intermediates such as a
dimerized diazomalonate in the presence of rhodium
could possibly act as a carbene precursor. However, this
may only be formed in higher concentrations of di-
methyl diazomalonate, low consumption of 1 being
observed until a certain excess of 3 is present. Alterna-
N-(2-Iodophenyl)-N-((2-(trimethylsilyl)ethoxy)methyl)-
furan-3-carboxamide (8). (2-(Chloromethoxy)ethyl)trimethyl-
silane (1.49 mL, 8.42 mmol) was added dropwise to a solution
of N-(2-iodophenyl)furan-3-carboxamide (635 mg, 2.03 mmol)
and sodium hydride (202 mg, 8.42 mmol) in THF (20 mL) at
0ꢀC under a nitrogen atmosphere. The reaction mixture was
allowed to stir for 11 h (mean while slowly warming up to
RT) and was then quenched by adding water (20 mL). The
Scheme 4
Scheme 3
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Carbene Induced Rearrangement Products from Two Furoquinolinone Scaffolds
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Scheme 5
reaction mixture was extracted with EtOAc (3 ꢁ 50 mL),
washing the combined organic layers with 1M NaOH (30 mL),
1M HCl (30 mL) and brine (20 mL), dried with MgSO4 and
concentrated under reduced pressure. Flash chromatography
(EtOAc:hexane/1:9) afforded 855 mg of 8 (95 %) as an oil. IR
(KBr, vmax): 2946, 2921, 2357, 2324, 1655, 1581, and 1471
cmꢂ1. UV (MeOH) kmax(e): 206.0 nm (14577), 226.2 nm
using (EtOAc:hexane/1:1) as eluent mixture which afforded
0.90 g of furo[3,2-c]quinolin-4(5H)-one (84%) as an off white
solid. 1H NMR (DMSO-d6, 400 MHz): d 7.04 (d, J 2.0 Hz,
1H, H-3), 7.25 (app t, J 7.4 Hz, 1H, H-8), 7.47 (app d, J 7.4
Hz, 1H, H-7), 7.53 (app t, J 7.4 Hz, 1H, H-9) 7.88 (d, J 7.4
Hz, 1H, H-6), 8.06 (d, J 2.0 Hz, 1H, H-2), 11.73 ( br s, 1H,
NH). 13C NMR (DMSO-d6, 100 MHz): d 108.4, 111.9, 116.2,
116.7, 120.8, 122.9, 130.1, 137.7, 146.1, 156.1, 159.5. MS
(ESI): m/z 185 [MþH]þ.
1
(10829). H NMR (CDCl3, 500 MHz): d 0.03 (s, 9H, SiMe3),
0.99 (m, J 10 Hz, 2H, H-2000), 3.77 (app d, J 5 Hz, 2H, H-1000),
4.57 (d, J 10.5 Hz, 1H, H-100), 5.81 (d, J 9 Hz, 1H, H-1b00),
6.28 (s, 1H, H-4), 6.73 (s, 1H, H-5), 7.16 (app t, J 7.5 Hz, 1H,
H-40), 7.20 (s, 1H, H-2), 7.37 (d, J 8.0 Hz, 1H, H-60), 7.45
(app t, J 8.0 Hz, 1H, H-50), 7.96 (d, J 8.0 Hz, 1H, H-30). 13C
NMR (CDCl3, 125 MHz) d 0.0 (SiMe3), 18.5 (C-2000), 66.9 (C-
1000), 77.3 (C-100), 101.4 (C-20), 111.4 (C-4), 121.9 (C-3), 129.7
(C-50), 130.9 (C-40), 132.0 (C-60), 140.4 (C-30), 142.5 (C-5),
143.8 (C-10), 145.9 (C-2), 163.7 (C¼¼O). MS (ESI): m/z 445
[MþH]þ, 467 [MþNa]þ, 910 [2MþNa]þ. Anal. Calcd. for
C17H22INO3Si: C, 46.05; H, 5.00; N, 3.16. Found: C, 46.09;
H, 5.01; N, 3.02.
(4-Chlorofuro[3,2-c]quinoline). A mixture of furo[3,2-
c]quinolin-4(5H)-one (0.87 g, 4.7 mmol), phosphorusoxychlor-
ide (10.0 mL) and water (0.5 mL) was refluxed at 135 ꢀC for
4 h. The cold reaction mixture was quenched by adding water
(10 mL) and with 25% ammonia. The aqueous layer was
extracted with DCM (3 ꢁ 150 mL) and EtOAc (3 ꢁ 150 mL).
The organic layers were combined, dried with MgSO4 and
concentrated under reduced pressure to afford 0.90 g of the
desired 4-chlorofuro[3,2-c]quinoline (94%). 1H NMR (CDCl3,
400 MHz): d 7.03 (d, J 2.2 Hz, 1H, H-3), 7.64 (m, 1H, H-8),
7.73 (m, 1H, H-7), 7.82 (d, J 2.2 Hz, 1H, H-2), 8.14 (dd,
J 8.0, 2.0 Hz, 1H, H-9), 8.25 (dd, J 7.4, 2.0 Hz, 1H, H-6). 13C
NMR (CDCl3, 100 MHz): d 106.3, 116.6, 119.8, 120.1, 127.2,
128.8, 129.2, 144.3, 145.0, 145.2, 156.4. MS (ESI): m/z 204
[MþH]þ.
5-((2-(Trimethylsilyl)ethoxy)methyl)furo[3,2-c]quinolin-4
(5H)-one (9). A mixture of 8 (90 mg, 0.20 mmol), KOAc (26
mg, 0.26 mmol), n-Bu4NCl (11 mg, 0.04 mmol), and PdO (2.5
mg, 0.02 mmol) was stirred in DMA (0.4 mL) at 150ꢀC under
a nitrogen atmosphere for 18 h. The crude mixture was then
concentrated under reduced pressure followed by flash chroma-
tography (EtOAc:hexane/15:85) to afford 55 mg of 9 (87%) as
a slightly yellowish solid. Mp 61–62ꢀC. IR (KBr, vmax): 3158,
3133, 2949, 2900, 1662, 1584, and 1499 cmꢂ1. UV (MeOH)
4-Methoxyfuro[3,2-c]quinoline (2). A mixture of the 4-
chlorofuro[3,2-c]quinoline (125 mg, 0.49 mmol) and a metha-
nolic solution of sodium methoxide (approximately 1.2 M,
generated from 230 mg sodium in 10 mL of methanol) at RT
under nitrogen atmosphere, was stirred until all starting mate-
rial was consumed (monitored by TLC). The reaction mixture
was extracted with EtOAc (3 ꢁ 100 mL). The organic layers
were combined, dried with MgSO4 and concentrated under
reduced pressure. Purification by flash chromatography (EtOA-
k
max(e): 227 nm (38358), 276 nm (7485), 286 nm (8934), 316
1
nm (9261), 331 nm (9435). H NMR (CDCl3, 500 MHz): d -
0.022 (s, 9H, H-SiMe3), 0.96 (t, J 8.5, 7.5 Hz, 2H, H-200),
3.74 (t, J 8.5, 8 Hz, 2H, H-100), 5.86 (s, 2H, H-10), 7.08 (s, 1H,
H-3), 7.35 (app t, J 7.5 Hz, 1H, H-8), 7.56 (app t, J 8.0 Hz,
1H, H-7), 7.65 (s, 1H, H-2), 7.72 (d, J 8.0 Hz, 1H, H-6), 8.02
(d, J 8.1 Hz, 1H, H-9). 13C NMR (CDCl3, 125 MHz) d 0.0
(SiMe3), 18.4 (C-200), 66.6 (C-100), 71.7 (C-10), 108.8 (C-3),
113.7 (C-3a), 115.1 (C-9a), 116.8 (C-6), 121.3 (C-9), 123.1
(C-8), 129.8 (C-2), 137.9 (C-5a), 144.3 (C-7), 156.1 (C-9b),
160.2 (C¼¼O). MS (ESI): m/z 316 [MþH]þ, 338 [MþNa]þ.
Anal. Calcd. for C17H21NO3Si: C, 64.73; H, 6.71; N, 4.44.
Found: C, 64.76; H, 6.70; N, 4.45.
1
c:hexane/0 to 2.5:100 to 97.5) afforded 100 mg of 2 (80%). H
NMR (CDCl3, 400 MHz): d 4.20 (s, 3H, OMe), 6.95 (m, 1H,
H-3), 7.46 (app t, J 7.2 Hz, 1H, H-8), 7.61 (app t, J 7.2 Hz,
1H, H-7), 7.72 (m, 1H, H-2), 7.95 (app d, J 7.2 Hz, 1H, H-6),
8.15 (app d, J 7.2 Hz, 1H, H-9). 13C NMR (CDCl3, 100
Scheme 6
Furo[3,2-c]quinolin-4(5H)-one (4). To a premixed solution
of acetyl chloride (43 mL), ethanol (73 mL) and water (5 mL),
was added 9 (1.82 g, 5.77 mmol) at RT with stirring. After all
substrate was dissolved, the reaction flask was fitted with a
reflux condenser and heated to 80ꢀC for 11 h, and the reaction
mixture was then concentrated under reduced pressure. Purifi-
cation was straightforward by flash chromatography when
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K.-F. Lindahl, A. Carroll, R. J. Quinn, and J. A. Ripper
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Scheme 7
MHz): d 53.7 (OMe), 105.4 (C-3), 111.4 (C-3a), 116.0 (C-9a),
120.1 (C-9), 124.4 (C-8), 127.7 (C-6), 128.6 (C-7), 144.3 (C-
1), 144.5 (C-5a), 157.64 (C-9b), 157.68 (C-4). MS (ESI): m/z
200 [MþH]þ.
[MþH]þ, 612 [MþNa]þ. HRMS Calcd. for C27H28NO14
[MþH]þ: 590.1504. Found: 590.1495.
Dimethyl 5-methoxy-2H-pyrano[3,2-c]quinoline-2,2-dicar-
boxylate (7). To a solution of 2 (100 mg, 0.5 mmol) and dir-
hodium tetraacetate (4.95 mg, 0.01 mmol, 2 mol %) in DCM
(2.5 mL) under nitrogen atmosphere, was added a solution of
dimethyl diazomalonate (293 mg, 1.85 mmol, 3.7 eq) in DCM
(0.5 mL) over 3 h period followed by 17 h stirring at ambient
temperature (monitored by tlc). The crude reaction mixture
was then filtered through a short silica plug using EtOAc as
eluent (2 ꢁ 20 mL), dried with MgSO4 and concentrated in
vacuo. Flash chromatography (EtOAc:hexane/1:9) afforded 63
mg of 7 as a white solid (38%). Mp 85–86ꢀC. IR (KBr, vmax):
3101, 3015, 2954, 1761, 1740, 1642, 1605, 1569, 1507, 1475
cmꢂ1. UV (MeOH) kmax(e): 229 (4083), 254 (2936), 263
Rearrangement/CH-insertion products (5) and (6). To a
solution of 1.30 (100 mg, 0.50 mmol) and dirhodium tetraace-
tate (5 mg, 0.01 mmol, 2 mol %) in DCM (2.5 mL) under a
nitrogen atmosphere was added a solution of dimethyl diazo-
malonate (293 mg, 1.85 mmol, 3.7 eq) in DCM (0.5 mL) over
3 h period followed by 17 h stirring at ambient temperature
(monitored by tlc). The crude was then filtered through a short
silica plug using EtOAc as eluent (2 ꢁ 20 mL), dried with
MgSO4 and concentrated in vacuo. Flash chromatography
(EtOAc:hexane/1:1) afforded 180 mg of a clear oil as a mix-
ture of the two products, 5 and 6, in the ratio of 75:25.
Reverse phase chromatography (HPLC, MeOH:H2O/7:3)
afforded an analytically pure sample of each product.
1
(2520), 317 (982) nm. H NMR (CDCl3, 500 MHz): d 3.86 (s,
2 ꢁ 3H, 2 ꢁ COOMe), 4.09 (s, 3H, OMe), 6.05 (d, J 10.0 Hz,
1H, H-3), 6.97 (d, J 10.0 Hz, 1H, H-4), 7.39 (dd, J 7.0, 1.0
Hz, 1H, H-9), 7.62 (dd, J 7.0, 1.0 Hz, 1H, H-8), 7.77 (d, J 8.0
Hz, 1H, H-7), 8.19 (d, J 8.0 Hz, 1H, H-10). 13C NMR (CDCl3,
125 MHz): d 53.86 (C-2, 2 ꢁ COOMe), 53.89 (C-5, OMe),
101.4 (C-4a), 82.3 (C-2), 116.9 (C-3), 117.7 (C-10a), 120.9
(C-4), 122.4 (C-10), 124.2 (C-9), 127.2 (C-7), 130.7 (C-8),
147.2 (C-6a), 155.4 (C-10b), 158.7 (C-5), 167.0 (C-2, 2 ꢁ
COOR). MS (ESI): m/z 330 [MþH]þ, 352 [MþNa]þ, 298 [M-
CH3O]þ. HRMS Calcd. for C17H16NO6 [MþH]þ: 330.0972.
Found 330.0960.
Ethyl 5,7-dimethyl-6-oxo-5,6b,7,7a-tetrahydro-6H-cyclopro-
pa[4,5]furo[3,2-c]quinoline-7-carboxylate (9). To a solution of
2 (482 mg, 2.41 mmol) and dirhodium tetraacetate (24 mg,
0.05 mmol, 2 mol %) in DCM (15 mL) under a nitrogen
atmosphere was added a solution of ethyl 2-diazopropanoate
(8) (988 mg, 7.71 mmol, 3.2 eq) in DCM (5 mL) over 1 h pe-
riod followed by 1 h stirring at ambient temperature. The
crude reaction mixture was then filtered through a short silica
plug using EtOAc as eluent (3 ꢁ 20 mL), dried with MgSO4
and concentrated in vacuo. Reverse phase flash chromatogra-
phy (MeOH:H2O/7:3) afforded 314 mg of 9 as a white solid
(43%). Mp 141–142ꢀC. IR (KBr, vmax): 3081, 2974, 2929,
1716, 1659, 1593, and 1569 cmꢂ1. UV (MeOH) kmax(e): 224
(25226), 298 (3488), 324 (3880) nm. 1H NMR (CDCl3, 400
MHz): d 0.93 (s, 3H, H-10), 1.29 (t, J 7.2 Hz, 3H, H-200), 3.50
(d, J 5.6 Hz, 1H, H-6b), 3.73 (s, 3H, NMe), 4.19 (q, J 7.2 Hz,
2H, H-100), 5.18 (d, J 5.6 Hz, 1H, H-7a), 7.26 (dd, J 7.6, 1.2
Hz, 1H, H-2), 7.41 (d, J 8.4 Hz, 1H, H-4), 7.61 (dd, J 7.6, 1.6
Hz, 1H, H-3), 7.77 (dd, J 7.6, 1.2 Hz, 1H, H-1). 13C NMR
(CDCl3, 125 MHz): d 6.6 (C-10), 14.5 (C-200), 20.2 (C-7), 29.6
(5): Mp 179ꢀC. IR (KBr, vmax): 3464, 3003, 2954, 1744,
1670, 1633, 1593, and 1437 cmꢂ1. UV (MeOH) kmax(e): 226
(12355), 283 (1738), 292 (1922) nm. 1H NMR (CDCl3, 600
MHz): d 3.63 (s, 3H, NMe), 3.73 and 3.91 (2 ꢁ s, 2 ꢁ OMe,
C-20), 3.80 and 3.85 (2 ꢁ s, 2 ꢁ OMe, C-2), 5.61 (d, J 10.8
Hz, 1H, H-3), 6.73 (d, J 10.8 Hz, 1H, H-10), 7.26 (dd, J 7.2,
3.0 Hz, 1H, H-8), 7.36 (d, J 8.4 Hz, 1H, H-6), 7.62 (app. t,
J 7.8 Hz, 1H, H-7), 7.88 (d, J 7.8 Hz, 1H, H-9). 13C NMR
(CDCl3, 125 MHz) d 29.4 (C-5), 46.7 (C-3), 52.8 and 53.1
(C-20, 2 ꢁ OMe), 53.7 and 54.2 (C-2, 2 ꢁ OMe), 93.5 (C-2),
108.0 (C-20), 111.7 (C-9a), 115.0 (C-6), 122.5 (C-8), 124.0 (C-
9), 131.4 (C-3a), 132.5 (C-7), 141.4 (C-5a), 142.3 (C-10),
159.9 (C-4), 161.9 (C-9b), 164.1, and 164.7 (C-20, 2 ꢁ
COOR), 165.1 and 166.1 (C-2, 2 ꢁ COOR) MS (ESI): m/z
460 [MþH]þ, 482 [MþNa]þ. HRMS Calcd. for C22H22NO10
[MþH]þ: 460.1238. Found: 460.1252.
(6): Mp 199ꢀC. IR (KBr, vmax): 3460, 3007, 2954, 1752,
1666, 1638, and 1433 cmꢂ1. UV (MeOH) kmax(e): 229
(14802), 279 (2944), 290 (2931), 326 (2379) nm. 1H NMR
(CDCl3, 400 MHz): d 2.61 (d, J 11.0 Hz, 1H, H-30), 3.66 (s,
3H, NMe), 3.73, 3.82, 3.87, and 3.95 (4 ꢁ s, 4 ꢁ OMe), 3.78
(s, 2 ꢁ OMe), 5.15 (d, J 11.0 Hz, 1H, H-3), 7.28 (m, 1H, H-
8), 7.37 (d, J 8.5 Hz, 1H, H-6), 7.63 (app t, J 7.5 Hz, 1H, H-
7), 7.88 (d, J 8.0 Hz, 1H, H-9). 13C NMR (CDCl3, 100 MHz):
d 29.6 (C-5), 36.7 (C-30), 43.7 (C-20), 43.9 (C-3), 45.3 (C-10),
53.0, 53.2, 53.5, 53.6, 53.7 and 53.9 (6 ꢁ OMe), 92.7 (C-2),
108.9 (C-3a), 111.9 (C-9a), 114.7 (C-6), 122.1 (C-8), 123.8
(C-9), 132.1 (C-7), 141.4 (C-5a), 160.1 (C-4), 161.1 (C-9b),
164.4 and 166.0 (C-10, 2 x COOR), 166.2 and 166.3 (C-20, 2
ꢁ COOR), 167.5 and 167.9 (C-2, 2 ꢁ COOR). (ESI): m/z 590
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Carbene Induced Rearrangement Products from Two Furoquinolinone Scaffolds
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(NMe), 34.4 (C-6b), 61.5 (C-100), 72.8 (C-7a), 110.3 (C-6a),
111.8 (C-8b), 115.0 (C-4), 122.2 (C-2), 122.8 (C-1), 131.5 (C-
3), 140.6 (C-4a), 161.1 (C-6), 164.0 (C-8a), 173.3 (COOR).
MS (ESI): m/z 300 [MþH]þ, 322 [MþNa]þ. HRMS Calcd. for
C17H17NO4Na [MþNa]þ: 322.1049. Found: 322.1041.
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Ethyl 6-methoxy-7-methyl-7,7a-dihydro-6bH-cyclopropa[4,5]-
furo[3,2-c]quinoline-7-carboxylate (10). To a solution of 3 (100
mg, 0.50 mmol) and dirhodium tetraacetate (5 mg, 0.01 mmol,
2 mol %) in DCM (3.1 mL) under a nitrogen atmosphere was
added a solution of ethyl 2-diazopropanoate (8) (209 mg, 1.60
mmol, 3.2 eq) in DCM (1 mL) over 1 h period followed by 1
h stirring at ambient temperature. The crude reaction mixture
was then filtered through a short silica plug using EtOAc as
eluent (2 ꢁ 20 mL), dried with MgSO4 and concentrated
in vacuo. Flash chromatography (EtOAc:hexane/5:95) afforded
103 mg of 10 as a white solid (69%). Mp 105ꢀC. IR (KBr,
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v
max): 2979, 2949, 2938, 2899, 1707, 1637, 1604, and 1576
cmꢂ1. UV (MeOH) kmax(e): 234 (52189), 320 nm (22709) nm.
1H NMR (CDCl3, 500 MHz): d 0.86 (s, 3H, H-10), 1.33 (t, J
6.0 Hz, 3H, H-200), 3.48 (d, J 5.6 Hz, 1H, H-6b), 4.14 (s, 3H,
OMe), 4.23 (q, J 6.0 Hz, 2H, H-100), 5.25 (d, J 5.6 Hz, 1H, H-
7a), 7.36 (dd, J 6.8, 1.2 Hz, 1H, H-2), 7.61 (dd, J 7.2, 1.6 Hz,
1H, H-3), 7.86 (m, 2H, H-4 and H-1). 13C NMR (CDCl3, 125
MHz): d 6.6 (C-10), 14.5 (C-200), 20.1 (C-7), 33.1 (C-6b), 53.7
(OMe), 61.6 (C-100), 72.9 (C-7a), 106.5 (C-6a), 114.6 (C-8b),
121.1 (C-4), 124.0 (C-2), 127.5 (C-1), 130.1 (C-3), 147.4 (C-
4a), 160.4 (C-6), 166.2 (C-8a), 173.7 (COOR). MS (ESI): m/z
300 [MþH]þ, 322 [MþNa]þ. HRMS Calcd. for C17H18NO4
[MþH]þ: 300.1230. Found: 300.1221.
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Acknowledgments. This work was supported through a Griffith
Postgraduate Research Scholarship.
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet