The Witkop-Winterfeldt oxidation converts tetrahydropyridoindoles into pyrroloquinolones and cinnolines by an unprecedented scaffold rearrangement

Article abstract of DOI:10.1016/j.tet.2010.11.110

The Fischer indole reaction between phenylhydrazines and tosyl-4-piperidone furnishes tetrahydropyrido[4,3-b]indoles. In a Witkop-Winterfeldt-oxidation using ozone such indole derivatives are converted into medium-sized dicarbonyl ring systems, which cycl

Full text of DOI:10.1016/j.tet.2010.11.110

Tetrahedron 67 (2011) 965e970
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Tetrahedron
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The WitkopeWinterfeldt oxidation converts tetrahydropyridoindoles into
pyrroloquinolones and cinnolines by an unprecedented scaffold rearrangement
,
b
c
a,b,
Matthias Mentel a, Martin Peters a , Jorg Albering , Rolf Breinbauer
*
€
a Institute of Organic Chemistry, University of Leipzig, Johannisallee 29, 04103 Leipzig, Germany
b Institute of Organic Chemistry, Graz University of Technology, Stremayrgasse 9, 8010 Graz, Austria
c Institute of Chemistry and Technology of Materials, Graz University of Technology, Stremayrgasse 9, 8010 Graz, Austria
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 28 October 2010
Received in revised form 19 November 2010
Accepted 30 November 2010
Available online 14 December 2010
The Fischer indole reaction between phenylhydrazines and tosyl-4-piperidone furnishes tetrahy-
dropyrido[4,3-b]indoles. In a WitkopeWinterfeldt-oxidation using ozone such indole derivatives are
converted into medium-sized dicarbonyl ring systems, which cyclize to pyrroloquinolones. A detailed
study of the reaction intermediates and the characterization of a cinnoline betaine side product formed
by an unprecedented ring closure mechanism are reported.
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
Indole rearrangement
Cinnolines
Ozonolysis
Suzuki coupling
WitkopeWinterfeldt-oxidation
1. Introduction
opportunities presented by several intermediates lying along this
reaction sequence (Scheme 1).
The indole scaffold is present in many natural products and is
regarded as privileged scaffold for medicinal chemistry.
a
NTs
O
Consequently, numerous synthetic strategies have been developed
to give access to different varieties of this compound class.1 Fur-
thermore, the ring system is distinguished by an amazingly rich
choice of follow up reactions offering the opportunity for de-
rivatization reactions. Most notably, the indole ring can be con-
verted into other ring systems, leading to further privileged
structures. Among others, the oxospiroindole rearrangement,2 the
WitkopeWinterfeldt-oxidation to quinolones,3 and a recently
published Pd-catalyzed ring expansion4 to quinolines should be
mentioned in this context, offering considerable synthetic potential
following the idea of scaffold-diversifying reactions as a means to
increase the structural diversity of compound libraries.5 We have
recently reported about the solid phase synthesis of tetrahy-
R
N
H
O
4
b
NTs
R
O
R
a
+
NTs
N
H
NHNH2
1
2
3
c
O-
N
dropyridoindoles (tetrahydro-g-carbolines), which delivered upon
O
O
cleavage pyrrolo[3,2-b]quinolones a previously unknown ring
system.6 Having already addressed the scope of this reaction on
solid phase, we will now report about a scalable solution phase
synthesis for some of these heterocycles and discuss the synthetic
R
H
Ts
N
R
R
N
d
N+
+
N
H
N
H
HOOC
7
5
6
Scheme 1. Synthesis of pyrrolo[3,2-b]quinolones by WitkopeWinterfeldt-oxidation of
tetrahydro- -carbolines: (a) Fischer indole synthesis; (b) Witkop-oxidation; (c) Wit-
kopeWinterfeldt-oxidation; (d) Detosylation.
g
* Corresponding author. Tel.: þ43 316 873 32400; fax: þ43 316 873 32402;
e-mail address: breinbauer@tugraz.at (R. Breinbauer).
0040-4020/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.11.110

966
M. Mentel et al. / Tetrahedron 67 (2011) 965e970
2. Results and discussion
2.2. WitkopeWinterfeldt-oxidation of tetrahydro-1H-pyrido-
[4,3-b]indoles
2.1. Synthesis of tetrahydro-1H-pyrido-[4,3-b]indoles
The powerful WitkopeWinterfeldt oxidation conveniently
rearranges indoles into the corresponding quinolones.3 In the first
By classic Fischer indole synthesis N-toysl-4-piperidone (2) was
converted into the corresponding tetrahydro-
g
-carbolines 3a,b
step, oxidation of g-carboline 3b yields keto-lactam 4b (Scheme 4).
(Scheme 2). This initial step proved most challenging in the anal-
ogous solid phase synthesis,6 where it required water- and oxygen-
free conditions and was carried out under ZnCl2 catalysis for
a broad range of phenylhydrazine substrates. Here, acetic acid
effected the transformation in case of p-bromophenylhydrazine
hydrochloride within a few hours in very good yield without the
need for chromatographic purification when working under oxy-
gen-free conditions. Similarly, unsubstituted phenylhydrazine
afforded mainly the corresponding intermediate phenylhydrazone
and required additional treatment with trifluoroacetic acid to
quantitatively effect the [3,3]-sigmatropic rearrangement leading
to the formation of the indole nucleus.
The intrinsic instability of this intermediate due to facile formation
of the Camps cyclization product (via intramolecular condensation)
required careful handling and its purification by trituration at 0 ꢀC.
Thus, a one-pot reaction was considered as most efficient to
transform tosylated
g-carbolines 3a,b directly into the corre-
sponding dihydropyrrolo[3,2-b]quinolones 5a,b. Similarly as in our
solid phase reaction, ozone was well suited to achieve the oxidation
reaction,3,6 while pyridine acted as a reducing agent for the
assumed intermediate ozonide, because the resulting pyridine
N-oxide could be easily removed in an aqueous workup. Addition of
triethylamine led to smooth cyclization and aqueous washing
procedures effectively provided the desired compounds. The low to
moderate yields of isolated dihydropyrrolo[3,2-b]quinolones 5
could be attributed to the formation of a by-product, which in one
case was isolated and unambiguously identified as cinnoline
betaine 6b by NMR and X-ray analysis (Scheme 5) (Fig 1).9,10
NTs
a, b
88 %
N
H
NTs
NTs
O
O
a
Br
Br
3a
NTs
NTs
43 %
N
H
N
H
O
Br
2
c
3b
4b
90 %
N
H
Scheme 4. Ozonolysis of g-carboline leading to nine-membered keto-lactam: (a) O3,
CH2Cl2, ꢁ78 ꢀC, 5 min, then pyridine, ꢁ78 ꢀC to rt (1 h).
3b
Scheme 2. Synthesisoftetrahydro-1H-pyrido-[4,3-b]indoles:(a)Phenylhydrazine,AcOH,
70 ꢀC, 3.5 h; (b) 1,2-Dichloroethane, 3% trifluoroacetic acid, 70 ꢀC, 19 h; (c) 4-Bromophe-
nylhydrazine hydrochloride, AcOH, 70 ꢀC, 3.5 h.
O-
N
O
NTs
Ts
N
R
R
R
a
+
N+
N
H
N
H
The availability of bromine substituted indole derivatives pro-
vides the opportunity to introduce various substituents via Pd-
catalyzed transformations in order to create diversity. The struc-
tural class of biphenyls, another example of a privileged structure,7
can be accessed via Suzuki cross-coupling of indole 3b with aryl-
boronic acids under conditions reported by Buchwald et al.8 Again,
optimization of the reaction conditions in solution was less cum-
bersome, when compared to solid phase, and involved an aqueous
solvent system and extended reaction times in case of poorly sol-
uble, electron-deficient 4-formylphenylboronic acid. Biphenyl
derivatives 8a,b could be isolated in good yields after flash column
chromatography (Scheme 3).
R = H 3a
HOOC
6b 18 %
5a 36 %
R = Br 3b
5b 60 %
Scheme 5. WitkopeWinterfeldt-oxidation under conditions affording cyclised qui-
nolone products: (a) O3, CH2Cl2, ꢁ78 ꢀC, 15 min, then pyridine, ꢁ78 ꢀC to rt (2 h), then
Et3N, rt, o. n.
NTs
a
N
H
81 %
NTs
Br
Fig. 1. X-ray crystal structure of cinnoline betaine 6b.
8a
H
N
H
2.2.1. Mechanism of cyclization. During the optimization of the
WitkopeWinterfeldt oxidation on solid phase we had not noticed
any by-product formation, but rather accepted the relatively low
yielding sequence, a fact that could have well been attributed to
several other peculiarities of the polymer-bound reaction process.
The solution phase synthesis, however, soon revealed the presence
of another compound, which was separated from dihydropyrrolo
[3,2-b]quinolones 5 upon aqueous basic washing. Acidification of
the aqueous phase yielded a precipitate, which showed typical
O
NTs
3b
b
66 %
N
H
8b
Scheme 3. Suzuki cross-coupling with bromoindole 3b: (a) 1 mol % Pd(OAc)2, 2 mol %
SPhos, K3PO4, m-tolylboronic acid, toluene, 100 ꢀC, 24 h; (b) 1 mol % Pd(OAc)2, 2 mol %
SPhos, K3PO4, 4-formylphenylboronic acid, toluene/THF/H2O 5:6:1, 90 ꢀC, 45 h.

M. Mentel et al. / Tetrahedron 67 (2011) 965e970
967
characteristics of a carboxylic acid. Its actual structure could only be
determined when the compound eventually crystallized from
a DMSO solution and was subjected to X-ray analysis.
Generally, nucleophilic substitution at an electrophilic nitrogen
centre is best represented by the Raschig hydrazine synthesis.13
However, examples of this type of reaction involving electron-de-
ficient nitrogen nucleophiles are rare, and have not been reported
for tertiary sulfonamides but only for secondary sulfonamides in
alkaline solution.14 Thus, we cannot entirely rule out preceding
Taking into consideration the three-step mechanism of ozo-
nolysis as described by Criegee (Scheme 6),11
g
-carbolines 3 will
add a molecule of ozone on their C2eC3
p-bond and their cycli-
zation products will decompose into carbonyl and carbonyl oxide.
In another cycloaddition reaction ozonides will be formed, which
undergo reduction by pyridine to the observed keto-lactams 4.
Those are cyclised under elimination of water to dihydropyrrolo
[3,2-b]quinolones 5.
b-elimination of sulfinate under basic conditions, which would lead
to a much more reactive imine nitrogen nucleophile. Eventually,
ring closure would yield a mesomerism-stabilized hydrazinium
derivative, best represented as cinnoline betaine 6b (Scheme 7).
2.3. Detosylation of pyrrolo[3,2-b]quinolones
+O
-O
Sulfonamides can be regarded as one of the most stable nitrogen
protecting groups usually requiring reductive conditions for their
cleavage.15 However, in the present case, facile basic deprotection
was achieved favoured by the formation of an aromatic 14
O
O
O
O
NTs
O+
O
NTs
NTs
R
R
a
R
b
N
H
N
H
p-electron system. The use of DMF as co-solvent to ensure com-
N
-O
carbonyl
oxide
H
plete solubility of the tosyl protected compounds turned out to be
central to the success of the desired transformation. Under these
conditions, the reaction proceeds with slower kinetics even at rt
(Scheme 8).
primary ozonide
3
c
NTs
O
O
NTs
N
d
R
O
R
O
N
H
O
N
H
4
ozonide
N+
O-
O
O
e
S
N
O
O
H
N
R
R
a
H
O
HO
Ts
O
NTs
N
Ts
N
N
H
R
R
R
N
H
f
g
7a quant.
R = H 5a
R = Br 5b
N
H
N
H
N
O
OH
7b 99 %
H
H2O
5
Scheme 8. Detosylation of dihydropyrrolo[3,2-b]quinolones under basic conditions:
(a) DMF/Et3N 1:1, 80 ꢀC, 20 h.
Scheme 6. Proposed mechanism for the formation of dihydropyrrolo[3,2-b]quino-
lones: (a) Formation of the primary ozonide via 1,3-dipolar cycloaddition; (b) De-
composition into carbonyl carbonyl oxide; (c) 1,3-Dipolar cycloaddition; (d) Reduction;
(e) Keto-enol tautomerism; (f) 6-Enolendo-exo-trig cyclization; (g) Water elimination.
2.4. Bromination of pyrrolo[3,2-b]quinolones
The pyrrolo[3,2-b]quinolone itself might serve as a building
block for library syntheses. Considering its electronic properties,
pyrroloquinolone 7 seems to be perfectly suited to undergo selec-
tive electrophilic substitution reactions. The highest electron den-
sity is likely to be found in the pyrrole moiety. 1H NMR data suggest
the C-3 position as the by far most nucleophilic centre. This pre-
dicted selectivity was explored by using bromination as a repre-
sentative electrophilic aromatic substitution reaction. Bromination
with N-bromosuccinimide readily occurred at rt furnishing 9a,b in
good yields. Similar to the detosylation procedure, the reaction
proceeded without formation of by-products and succinimide and
bromine were removed in an aqueous workup (Scheme 9).
The formation of cinnoline betaines of type 6b from g-carbo-
lines 3 is unprecedented, but could involve the formation of an
O-acyl N-arylhydroxylamine in analogy to the rearrangement of
carbonyloxides into esters, lactones or acid anhydrides as postu-
lated by Criegee (Scheme 7).11
O
NTs
O
R
R
a
b
NTs
O
O+
N
NH
H
-O
O-acyl N-aryl
O
Criegee
S
hydroxylamine
intermediate
HO
O
O
O
H
N
H
N
O-
N
O
O
R
R
a
R
R
R
N+
N
H
N
H
N+
N+
O
N
H
Br
N
R = H 7a
-O
9a 74 %
9b 87 %
HO
-O
R = Br 7b
6b
O
O
Scheme 9. Selective bromination of pyrrolo[3,2-b]quinolones: (a) N-bromosuccini-
mide, AcOH, rt, 1 h.
Scheme 7. Mechanistic proposal for the formation of cinnoline betaines: (a) Re-
arrangement; (b) Sulfinic acid elimination and ring closure.
3. Conclusion
Such O-acyl N-arylhydroxylamines and their reactivity with
nucleophilic amines have been investigated by Boche as active
metabolites and the cause of carcinogenicity of aromatic amines.12
We could demonstrate that tetrahydro-1H-pyrido-[4,3-b]-indoles
can be subjected to WitkopeWinterfeldt-oxidation. Treatment with

968
M. Mentel et al. / Tetrahedron 67 (2011) 965e970
ozone leads to a nine-membered keto-lactam, which can either be
isolatedorinsitucyclisedtodihydropyrrolo[3,2-b]quinolones.Asside
products in the ozonolysis reaction alkyl cinnoline betaines are
(59.2 mmol, 1.0 equiv) 1-tosylpiperidin-4-one (2),16 500 mL AcOH
and 1.1 equiv phenylhydrazine derivative (1). The suspension was
degassed by vacuum/N2 cycles and slowly warmed to 70 ꢀC. If
a black mixture is obtained at this stage, this might be an indication
for residual oxygen, usually leading to decomposition and very low
yields of isolated compound after flash chromatography. After
stirring at 70 ꢀC for 3.5 h the solution was cooled to 0 ꢀC and 300 mL
degassed, cold (0 ꢀC) satd aq KOH was carefully added under N2
atmosphere. The resulting suspension was poured on ice in a 2 L
round-bottom flask and additional solid KOH was added under
cooling until pH 8 was reached. It is important that the temperature
of the reaction mixture is maintained below 25 ꢀC during the whole
process by providing sufficient external cooling with an ice-water
bath. After extraction with EtOAc (3ꢂ400 mL) the combined
organic layers were dried over MgSO4, filtrated, and concentrated
in vacuo [In case of incomplete conversion as detected by analytical
HPLC, the solid residue is taken up in 140 mL DCE and degassed by
bubbling Ar through it while immersing in an ultrasonic bath. Then
4 mL TFA are added and the mixture heated under Ar atmosphere at
70 ꢀC until HPLC analysis indicates complete conversion (19 h). The
solvent is evaporated under reduced pressure and TFA is co-evap-
orated with toluene (3ꢂ20 mL)]. The solid residue was suspended
in 150 mL pre-cooled (ꢁ18 ꢀC) CHCl3 and the mixture was ho-
mogenized by immersing the flask in an ultrasonic bath. A solid was
collected by filtration through a sintered glass funnel and washed
with cold CHCl3 before dried under high vacuum.
formed, which most likely might be formed via
a Criegee
intermediate. The unique electronic properties of the generated
pyrrolo[3,2-b]quinolones enable their derivatisation, e. g., via elec-
trophilic aromatic substitution, selectively on the pyrrole moiety. In
addition to the substitution pattern introducible in the Fischer indole
reaction by employing various phenylhydrazine derivatives,6 access
to a privileged structure building block is granted.
4. Experimental
4.1. General
Chemicals were purchased commercially and used without
purification unless otherwise stated. Phenylhydrazine was purified
by distillation and stored at 4 ꢀC under Ar atmosphere. Dichloro-
methane (DCM) and MeOH were dried over CaH2 and distilled under
Ar atmosphere before use. Toluene and pyridine were dried by
ꢀ
storing over molecular sieve (MS) 4 A. Tetrahydrofuran (THF) was
dried by heating at reflux temperature under Ar atmosphere over
Na, until benzophenone indicated dryness bya deep blue colour. Dry
THF was usually prepared directly prior to its use. 1H and 13C NMR
spectra were recorded on Varian Gemini 2000, Varian Mercury plus
300 and 400 and Bruker DRX 400 spectrometers and chemical shifts
are referenced to residual protonated solvent signals as internal
standard. Mass spectra were obtained with a Bruker Daltonics 7 T
APEX II FT-ICR-MS (ESI, high resolution), a Jeol SX 102 A (FAB, high
resolution, matrix: m-nitrobenzylalcohol) and a Bruker Esquire3000
plus (ESI, low resolution). The X-ray single-crystal data of compound
6bwerecollected on a Bruker-AXS Kappa APEX IICCD diffractometer
at 100(2) K. HPLC was performed on a Knauer Smartline instrument
with Autosampler 3800, Manager 5000 Low Pressure Gradient,
Pump 1000, UV Diode Array Detector 2600 and Fraction Collector
Isco Foxy Junior FC100. For analytical measurements a Macher-
eyeNagel EC 125/4 Nucleodur 100-3 C18 ec column with a CC 8/4
Nucleodur 100-5 C18 ec pre-column was used. A general acetoni-
trile/water gradient with 0.05% (v/v) TFA at a flow rate of 0.5 mL/min
was applied (0.0e6.0 min: 10% MeCN const., 6.0e26.0 min: 100%
MeCN lin. gradient, 26.0e32.0 min: 100% MeCN const.,
32.0e32.5 min: 10% MeCN lin., 32.5e40.0 min: 10% MeCN lin.). The
elution time and the local maxima in the absorption spectrum be-
tween 200 and 500 nm are given. Semi-preparative HPLC was car-
ried out on the same instrument utilizing a VP 125/21 Nucleodur
100-5 C18 ec column with VP 50/21 Nucleodur 100-5 C18 ec pre-
column at a flow rate of 20 mL/min. As a general rule for HPLC
purifications, the gradient was adjusted for each semi-preparative
run according to the observed peak elution time/percentage of
MeCN in the analytical chromatogram, usually starting at a MeCN
value 30% lower than that detected for elution of the compound in
the analytical run. Silica gel chromatography was performed with
Merck silica gel 60 (230e400 mesh). Analytical thin layer chroma-
tography (TLC) was performed using Merck silica gel 60-F254 and
Phenylhydrazine (1a) (7.04 g, 65.1 mmol) yield after TFA treat-
ment 17.0 g (52 mmol, 88%) 2-tosyl-2,3,4,5-tetrahydro-1H-pyrido
[4,3-b]indole (3a)17 as slightly orange-white solid. Mp 188e190 ꢀC;
1H NMR (400 MHz, DMSOd6):
d
¼10.95 (s, 1H, NH), 7.74 (d,
3J¼8.3 Hz, 2H, AreH), 7.42 (d, 3J¼8.1 Hz, 2H, AreH), 7.39 (d,
3J¼7.6 Hz, 1H, AreH), 7.27 (d, 3J¼8.0 Hz, 1H, AreH), 7.03 (ddd,
3J¼8.2, 7.2 Hz, 4J¼1.1 Hz, 1H, AreH), 6.95 (ddd, 3J¼7.9, 7.2 Hz,
4J¼1.0 Hz, 1H, AreH), 4.25 (s, 2H, CH2N), 3.41 (t, 3J¼5.8 Hz, 2H,
CH2N), 2.83 (t, 3J¼5.6 Hz, 2H, CH2), 2.37 (s, 3H, CH3); 13C NMR
(100 MHz, DMSOd6, APT):
d
¼143.5 (Cq, CAr), 135.8 (Cq, CAr), 133.7
(Cq, CAr), 131.7 (Cq, CAr), 129.8 (CH, CAr), 127.3 (CH, CAr), 124.9 (Cq,
CAr), 120.8 (CH, CAr), 118.6 (CH, CAr), 117.2 (CH, CAr), 111.0 (CH, CAr),
104.1 (Cq, CAr), 43.5 (CH2, CH2N), 43.0 (CH2, CH2N), 23.1 (CH2), 21.0
(CH3); HRMS (FAB): m/z: calcd for C18H19N2O2Sþ [MþH]þ: 327.1162,
found 327.1172; HPLC: tR¼26.9 min, lmax¼224, 273 nm.
4-Bromophenylhydrazine hydrochloride (1b) (14.6 g, 65.1 mmol)
yield 21.0 g (53 mmol, 90%) 8-bromo-2-tosyl-2,3,4,5-tetrahydro-1H-
pyrido[4,3-b]indole (3b) as
a brownish-white-grey solid. Mp
170e171 ꢀC; 1H NMR (400 MHz, DMSOd6):
d¼11.12 (s, 1H, NH), 7.74
(d, 3J¼8.2 Hz, 2H, AreH), 7.64 (d, 4J¼1.7 Hz, 1H, AreH), 7.40 (d,
3J¼8.2 Hz, 2H, AreH), 7.24 (d, 3J¼8.6 Hz, 1H, AreH), 7.13 (dd,
3J¼8.6 Hz, 4J¼1.9 Hz,1H, AreH), 4.25 (s, 2H, CH2N), 3.41 (t, 3J¼5.7 Hz,
2H, CH2N), 2.84 (t, 3J¼5.3 Hz, 2H, CH2), 2.36 (s, 3H, CH3); 13C NMR
(100 MHz, DMSOd6, APT):
d
¼143.4 (Cq, CAr),134.5 (Cq, CAr),133.6 (Cq,
CAr), 133.5 (Cq, CAr), 129.7 (CH, CAr), 127.3 (CH, CAr), 126.7 (Cq, CAr),
123.1 (CH, CAr), 119.7 (CH, CAr), 112.8 (CH, CAr), 111.2 (Cq, CAr), 104.1
(Cq, CAr), 43.3 (CH2, CH2N), 42.8 (CH2, CH2N), 23.1 (CH2), 21.0 (CH3);
HRMS (MeOH, ESIþ): m/z: calcd for C18H17BrN2NaO2Sþ [MþNa]þ:
427.0086; found 427.0090; HPLC: tR¼31.3 min, lmax¼229, 287 nm.
spots were visualized using a UV lamp (
l
¼254, 366 nm) or by
treatment with cerium ammonium molybdate solution (CAM; 2 g Ce
(SO4)2, 50 g (NH4)2MoO4, 50 mL concentrated H2SO4 in 400 mL
water) followed by heating. Ozonizations were carried out on
a Fischer Ozongenerator 500. Melting points were determined with
a Boetius melting-point apparatus and are uncorrected.
4.2.1. 8-m-Tolyl-2-tosyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole
(8a). A 10 mL Schlenk tube was dried under vacuum, filled with Ar
and charged consecutively with 2.2 mg (0.010 mmol, 1.0 mol %) Pd
(OAc)2, 8.2 mg (0.020 mmol, 2.0 mol %) S-PHOS,8 0.204 g
(1.50 mmol, 1.5 equiv) m-tolylboronic acid, 0.425 g (2.00 mmol,
2.0 equiv) mortar-powdered, anhydrous K3PO4, 0.405 g (1.00 mmol,
1.0 equiv) 8-bromo-2-tosyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]in-
dole (3b), and 3 mL toluene. The mixture was degassed by vacuum/
Ar cycles. A yellow-brown suspension formed and the mixture was
heated at 100 ꢀC in a sealed tube for 24 h. After cooling to rt 1 mL
4.2. Synthesis of tetrahydro-g-carbolines (3) general
procedure
A 1 L three-neck round-bottom flask equipped with a reflux
condenser and gas inlet was charged consecutively with 15.0 g

M. Mentel et al. / Tetrahedron 67 (2011) 965e970
969
Et2O was added, the mixture filtrated through a pad of silica in
a sintered glass funnel, eluted with EtOAc (1ꢂ50 mL) and EtOAc/
MeOH (1:1, 1ꢂ50 mL) and concentrated to dryness. 0.43 g yellow-
brown residue were obtained and subjected to flash column
chromatography [EtOAc/cyclohexane 1:9 to EtOAc/cyclohexane
7:3; Rf¼0.41 (EtOAc/cyclohexane 2:3, CAM)] to obtain a cloudy-
yellow oil that upon trituration with DCM and evaporation crys-
tallized to furnish 0.338 g (0.811 mmol, 81%) of the title compound
as a yellowish-white solid. Mp 180e185 ꢀC; 1H NMR (400 MHz,
222e225 ꢀC; 1H NMR (400 MHz, CDCl3):
d
¼7.72 (d, 4J¼2.3 Hz, 1H,
8-H), 7.66 (dd, 3J¼8.4 Hz, 4J¼2.3 Hz, 1H, 10-H), 7.60 (d, 3J¼8.3 Hz,
2H, 20-H, 60-H), 7.32 (d, 3J¼8.2 Hz, 2H, 30-H, 50-H), 7.11 (d, 3J¼8.2 Hz,
1H,11-H), 4.03 (s, 2H, 6-H), 3.48 (br t, 3J¼6.4 Hz, 2H, 4-H), 2.54 (br s,
2H, 3-H), 2.44 (s, 3H, CH3); 13C NMR (100 MHz, CDCl3, APT):
d
¼201.5 (Cq, C-7), 174.4 (Cq, C-2), 144.6 (Cq, C-40), 141.9 (Cq, C-11a),
135.2 (CH, C-10), 134.9 (Cq, C-10), 134.1 (CH, C-8), 131.3 (Cq, C-7a),
130.7 (CH, C-11), 130.3 (CH, C-30, C-50), 127.2 (CH, C-20, C-60), 123.9
(Cq, C-9), 59.9 (CH2, C-6), 49.0 (CH2, C-4), 36.0 (CH2, C-3), 21.7 (CH3).
The structural assignment was confirmed by 2-D NMR (HH-COSY,
HSQC, HMBC). HRMS (MeOH, ESIþ): m/z: calcd for
C18H17BrN2NaO4Sþ [MþNa]þ: 458.9985; found 458.9990; HPLC:
tR¼23.3 min, lmax¼216 nm.
CDCl3):
d
¼7.90 (s, 1H, NH), 7.77 (d, 3J¼8.3 Hz, 2H, AreH), 7.58 (d,
4J¼1.1 Hz, AreH), 7.46e7.41 (m, 2H, AreH), 7.39 (dd, 3J¼8.4 Hz,
4J¼1.7 Hz, 1H, AreH), 7.35e7.29 (m, 4H, AreH), 7.14 (d, 3J¼7.5 Hz,
1H, AreH), 4.41 (s, 2H, CH2N), 3.52 (t, 3J¼5.7 Hz, 2H, CH2N), 2.87 (t,
3J¼5.7 Hz, 2H, AreH), 2.44 (s, 3H, CH3), 2.42 (s, 3H, CH3); 13C NMR
(100 MHz, CDCl3, APT):
d
¼143.7 (Cq, CAr), 142.4 (Cq, CAr), 138.3 (Cq,
4.3. Synthesis of tosyl dihydropyrrolo[3,2-b]quinolones (5)
general procedure
CAr), 135.5 (Cq, CAr), 134.1 (Cq, CAr), 133.5 (Cq, CAr), 131.7 (Cq, CAr),
129.9 (CH, CAr), 128.7 (CH, CAr), 128.2 (CH, CAr), 127.7 (CH, CAr), 127.3
(CH, CAr), 126.0 (Cq, CAr), 124.5 (CH, CAr), 121.7 (CH, CAr), 116.1 (CH,
CAr), 111.1 (CH, CAr), 106.5 (Cq, CAr), 43.6 (CH2, CH2N), 43.2 (CH2,
CH2N), 23.9 (CH2, CH2), 21.7 (CH3), 21.7 (CH3); HRMS (FAB): m/z:
calcd for C25H24N2O2Sþ [M]þ: 416.1553; found 416.1538; HPLC:
tR¼31.3 min, lmax¼254 nm.
A 250 mL Schlenk tube was charged with 1.0 equiv tosyl
g-carboline 3 and 150 mL DCM. The yellow-brown suspension was
homogenized by immersing the tube in an ultrasonic bath and
cooled to ꢁ78 ꢀC. Then a stream of O3 was passed through the
solution until a blue colour developed (15 min). The O3 stream was
continued for 5 min. Then surplus O3 was removed by passing
a stream of N2 through the solution for 10 min and the blue colour
completely vanished. Afterwards 1.55 mL (1.52 g, 19.3 mmol,
1.3 equiv) pyridine was added to the cold (ꢁ78 ꢀC) mixture. The
mixture was allowed to warm to rt (2 h) before 5.34 mL (3.89 g,
38.4 mmol, 2.6 equiv) Et3N were added. After stirring at rt over-
night the brown suspension was concentrated under reduced
pressure to dryness. The residue was suspended in 100 mL 10% aq
KHSO4 and homogenized by immersing in an ultrasonic bath for
30 min. A light-brown solid was collected by filtration through
a sintered glass funnel and washed with H2O (4ꢂ30 mL). The solid
was suspended in 100 mL 10% aq NaHCO3 and homogenized by
immersing in an ultrasonic bath for 60 min. The solid was collected
by filtration through a sintered glass funnel and washed with water
(5ꢂ30 mL). The filter cake was dried by sucking air through the
€
4.2.2. 4-(2-Tosyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indol-8-yl)
benzaldehyde (8b). A 10 mL Schlenk tube was dried under vacuum,
filled with Ar and charged consecutively with 0.010 g (0.025 mmol,
1.0 equiv) 3b, 0.006
g
(0.037 mmol, 1.5 equiv) 4-for-
mylphenylboronic acid, 0.011 g (0.049 mmol, 2.0 equiv) mortar-
powdered, anhydrous K3PO4, 1 mL toluene/THF (1:1), 0.2 mg
(0.49 mmol, 2.0 mol %) SPhos and 0.2 mL (0.25 mmol, 1.0 mol %) of
a 1.2 mg/mL (THF/H2O 1:1) Pd(OAc)2 solution. The clear colourless
suspension was degassed by vacuum/N2 cycles. Stirring was per-
formed at 90 ꢀC until HPLC analysis indicated complete conversion
(45 h). The mixture was cooled to rt and 3 mL EtOAc were added.
After filtration through a pad of silica and elution with 50 mL EtOAc,
the filtrate was concentrated to dryness.Yellow oil (0.020 g) was
obtained and subjected to semi-preparative HPLC. Title compound
(7 mg, 0.016 mmol, 66%) was isolated as a yellow amorphous solid.
funnel on
overnight.
a Buchner flask under membrane pump vacuum
1H NMR (300 MHz, CDCl3):
d
¼10.06 (s, 1H, CHO), 7.95 (d, 3J¼8.2 Hz,
2H, AreH), 7.91 (s, 1H, NH), 7.80 (d, 3J¼6.6 Hz, 2H, AreH), 7.77 (d,
3J¼6.6 Hz, 2H, AreH), 7.67 (s, 1H, AreH), 7.46 (dd, 3J¼8.5 Hz,
4J¼1.6 Hz, 1H, AreH), 7.38 (d, 3J¼8.5 Hz, 1H, AreH), 7.32 (d,
3J¼8.1 Hz, 1H, AreH), 4.43 (s, 2H, CH2N), 3.56 (t, 3J¼5.7 Hz, 2H,
CH2N), 2.93 (t, 3J¼5.6 Hz, 2H, CH2), 2.42 (s, 3H, CH3) ppm; 13C NMR
Compound 3a (4.82 g, 14.8 mmol) yield 1.80 g (5.29 mmol, 36%)
1-tosyl-2,3-dihydro-1H-pyrrolo[3,2-b]quinolin-9(4H)-one (5a) as
a
slightly brownish-white solid. Mp 207e209 ꢀC; 1H NMR
(200 MHz, DMSOd6):
d
¼12.06 (s, 1H, NH), 8.15 (dd, 3J¼8.1 Hz,
4J¼1.3 Hz, 1H, AreH), 7.65 (d, 3J¼8.3 Hz, 1H, AreH), 7.61 (overlaid
ddd, 3J¼8.4, 7.1 Hz, 4J¼1.2 Hz, 1H, AreH), 7.46 (d, 3J¼8.2 Hz, 1H,
AreH), 7.34 (d, 3J¼8.0 Hz, 2H, AreH), 7.36e7.30 (overlaid m, 1H,
AreH), 3.99 (t, 3J¼7.6 Hz, 2H, CH2N), 2.53e2.47 (overlaid m,
CH2CH2N), 2.36 (s, 3H, CH3); 13C NMR (100 MHz, DMSOd6, APT):
(100 MHz, DMSOd6, APT):
d
¼192.6 (CH, CHO), 147.6 (Cq, CAr), 143.5
(Cq, CAr), 136.1 (Cq, CAr), 134.1 (Cq, CAr), 133.6 (Cq, CAr), 133.0 (Cq, CAr),
130.1 (CH, CAr), 129.8 (CH, CAr), 129.4 (Cq, CAr), 127.3 (CH, CAr), 126.9
(CH, CAr), 125.7 (Cq, CAr), 120.2 (CH, CAr), 116.4 (CH, CAr), 111.5 (CH,
CAr), 105.1 (Cq, CAr), 43.4 (CH2, CH2N), 43.0 (CH2, CH2N), 23.2 (CH2,
CH2), 21.0 (CH3) ppm; HPLC: tR¼26.9 min, lmax¼229, 281, 325 nm.
d
¼168.0 (Cq, C]O), 149.4 (Cq, CAr), 143.5 (Cq, CAr), 138.8 (Cq, CAr),
134.9 (Cq, CAr), 131.1 (CH, CAr), 129.5 (CH, CAr), 127.6 (CH, CAr), 126.6
(Cq, CAr), 125.5 (CH, CAr), 123.1 (CH, CAr), 121.6 (Cq, CAr), 118.0 (CH,
CAr), 50.1 (CH2, CH2N), 28.4 (CH2, CH2CH2N), 21.0 (CH3); HRMS
(MeOH, ESIþ): m/z: calcd for C18H16N2NaO3Sþ [MþNa]þ: 363.0774;
found 363.0773; HPLC: tR¼21.3 min, lmax¼219, 326 nm.
4.2.3. 9-Bromo-5-tosyl-3,4,5,6-tetrahydro-1H-1,5-benzodiazonine-
2,7-dione (4b). A Schlenk tube was filled with N2 and charged with
2.00 g (4.93 mmol, 1.0 equiv) 3b and 240 mL DCM. The solution was
cooled to ꢁ78 ꢀC before a stream of O3 was passed through the
solution until a blue colour developed (5 min). The O3 stream was
continued for 5 min. Then, surplus O3 was removed by passing
a stream of N2 through the solution for 5 min. 0.52 mL (6.41 mmol,
1.3 equiv) pyridine were added and the solution was allowed to
warm to rt (1 h). The orange solution was washed with H2O (2ꢂ),
dried over MgSO4, filtrated, and concentrated in vacuo. The residue
was suspended in 120 mL H2O/MeOH (1:1) and homogenized by
immersing in an ultrasonic bath. The mixture was kept at 0 ꢀC
overnight before a brown solid was collected by filtration. After
washing with H2O and drying under high vacuum 0.919 g
(2.10 mmol, 43%) of the title compound was obtained. Mp
Compound 3b (6.00 g, 14.8 mmol) yield 3.71 g (8.85 mmol, 60%)
7-bromo-1-tosyl-2,3-dihydro-1H-pyrrolo[3,2-b]quinolin-9(4H)-
one (5b) as a brownish-white solid. Mp 230e231 ꢀC; 1H NMR
(400 MHz, DMSOd6):
d
¼12.31 (s, NH), 8.23 (d, 4J¼2.2 Hz, 1H, 8-H),
7.76 (dd, 3J¼8.9 Hz, 4J¼2.2 Hz, 1H, 6-H), 7.65 (d, 3J¼8.1 Hz, 2H, 10-H,
60-H), 7.44 (d, 3J¼8.8 Hz, 1H, 5-H), 7.34 (d, 3J¼8.1 Hz, 2H, 20-H, 50-H),
4.00 (t, 3J¼7.5 Hz, 2H, 2-H), 2.52 (overlaid t, 3J¼7.7 Hz, 2H, 3-H), 2.36
(s, 3H, CH3); 13C NMR (75 MHz, DMSOd6, APT):
d¼166.6 (Cq, C-9),
150.1 (Cq, C-9a), 143.7 (Cq, C-40), 137.7 (Cq, C-4a), 134.8 (Cq, C-10),
133.9 (CH, C-6), 129.6 (CH, C-20, C-50), 128.2 (Cq, C-8a), 127.7
(overlaid CH, C-8), 127.6 (CH, C-10, C-60), 122.0 (Cq, C-3a), 120.7 (CH,
C-5), 116.0 (Cq, C-7), 50.2 (CH2, C-2), 28.5 (CH2, C-3), 21.1 (CH3). The

970
M. Mentel et al. / Tetrahedron 67 (2011) 965e970
structural assignment was confirmed by 2-D NMR (HH-COSY,
HSQC, HMBC). HRMS (MeOH, ESIþ): m/z: calcd for C18H16BrN2O3Sþ
[MþH]þ: 419.0060; found 419.0060; HPLC: tR¼21.3 min, lmax¼221,
263, 333 nm.
A by-product was collected from the NaHCO3 wash phase upon
acidification with concentrated HCl and filtration of the precipitate.
0.776 g (2.61 mmol, 18%) 6-bromo-2-(2-carboxyethyl)cinnolin-
2-ium-4-olate (6b) were obtained as a brownish-white solid. 1H
C
11H7BrN2NaOþ [MþNa]þ: 284.9634; found 284.9635; HPLC:
tR¼20.2 min, lmax¼243, 303, 351, 364 nm.
Compound 7b (0.300 g, 1.14 mmol) yield 0.340 g (0.994 mmol,
87%) 3,7-dibromo-1H-pyrrolo[3,2-b]quinolin-9(4H)-one (9b) as
a brown solid. Mp 292e294 ꢀC; 1H NMR (400 MHz, DMSOd6):
d
¼12.38 (s, 1H, NH), 11.81 (s, 1H, NH), 8.33 (s, 1H, 8-H), 7.76e7.73
(m, 2H, 6-H, 5-H), 7.66 (d, 3J¼3.0 Hz, 1H, 2-H); 13C NMR (100 MHz,
DMSOd6, APT):
d¼164.6 (Cq, C]O), 138.6 (Cq, CAr), 133.8 (Cq, CAr),
NMR (300 MHz, DMSOd6):
d
¼12.55 (br s, NH), 8.39 (s, 1H), 8.18 (d,
133.5 (CH, CAr), 128.3 (CH, CAr), 127.3 (CH, CAr), 123.2 (Cq, CAr), 120.3
(CH, CAr),119.7 (Cq, CAr),112.7 (Cq, CAr), 80.9 (Cq, C-3); HRMS (MeOH,
ESIþ): m/z: calcd for C11H7Br2N2Oþ [MþH]þ: 340.8920; found
340.8919; HPLC: tR¼23.0 min, lmax¼247, 258, 308, 357, 372 nm.
4J¼2.3 Hz, 1H, AreH), 7.90 (dd, 3J¼9.0 Hz, 4J¼2.3 Hz, 1H, AreH), 7.77
(d, 3J¼9.0 Hz, 1H, AreH), 4.70 (t, 3J¼6.8 Hz, 2H, CH2N), 3.06 (t,
3J¼6.8 Hz, 2H, CH2CH2N) ppm.; 13C NMR (75 MHz, DMSOd6, APT):
d¼171.6 (Cq, C]O), 168.6 (Cq, C]O), 147.5 (Cq, CAr), 135.7 (CH, CAr),
134.2 (CH, CAr), 128.7 (CH, CAr), 126.7 (Cq, CAr), 125.1 (CH, CAr), 120.9
(Cq, CAr), 59.8 (CH2, CH2N), 33.3 (CH2, CH2CH2N) ppm. 2D-NMR
analytical (HH-COSY, HSQC, HMBC) and X-ray data is given in the
Supplementary data. HRMS: (MeCN/DMSO, ESIþ): m/z: calcd for
C11H10BrN2Oþ3 [MþH]þ: 296.9869; found 296.9871; HPLC:
tR¼18.7 min, lmax¼215, 260, 358, 375 nm.
Acknowledgements
€
We are indebted to Heike Petzold, Sven Rotering, Sebastian Rauch
and Franziska Schramm for skilful technical assistance, Dr. Lothar
Hennig for help in interpreting NMR data and Ramona Oehme for
acquiring MS data. Financial support by the DFG (Br-2324/1-1) and
the University of Leipzig is gratefully acknowledged.
4.4. Detosylation of tosyl dihydropyrrolo[3,2-b]quinolones
(5) general procedure
Supplementary data
A 250 mL round-bottom flask was charged with tosyl dihy-
dropyrrolo[3,2-b]quinolone 5 and 50 mL DMF. The suspension was
homogenized by immersing the flask in an ultrasonic bath for
60 min before 50 mL Et3N were added. The mixture was heated at
80 ꢀC until HPLC analysis indicated complete conversion (20 h). The
solvents were evaporated under reduced pressure and the residue
was suspended in 70 mL 10% aq NaHCO3 and homogenized by
immersing in an ultrasonic bath for 10 min. A solid was collected by
filtration and washed with H2O until neutral reaction of the filtrate
before drying under high vacuum.
Supplementary data related to this article can be found online at
doi:10.1016/j.tet.2010.11.110. These data include MOL files and
InChIKeys of the most important compounds described in this
article.
References and notes
1. Reviews: (a) Humphrey, G. R.; Kuethe, J. T. Chem. Rev. 2006, 106, 2875e2911; (b)
Gribble, G. W. J. Chem. Soc., Perkin Trans. 1 2000, 1045e1075; (c) Sundberg, R. J.
Indoles; Academic: London, 1996.
Compound 5a (1.70 g, 5.0 mmol) yield 1.06 g (5.8 mmol, quant.)
1H-pyrrolo[3,2-b]quinolin-9(4H)-one (7a)6 as a light-brown solid.
Mp 126e130 ꢀC; HPLC: tR¼16.2 min, lmax¼239, 304, 349, 362 nm.
Compound 5b (1.66 g, 3.96 mmol) yield 1.03 g (3.92 mmol, 99%)
7-bromo-1H-pyrrolo[3,2-b]quinolin-9(4H)-one (7b)6 as a light-
brown solid. Mp 231e233 ꢀC; HPLC: tR¼19.2 min, lmax¼244, 309,
356, 372 nm.
2. Review: Marti, C.; Carreira, E. M. Eur. J. Org. Chem. 2003, 2209e2219.
3. (a) Review: Mentel, M.; Breinbauer, R. Curr. Org. Chem. 2007, 11, 159e176; (b)
Witkop, B.; Patrick, J. P.; Rosenblum, M. J. Am. Chem. Soc. 1951, 73, 2641e2647;
(c) Winterfeldt, E. Liebigs Ann. Chem. 1971, 745, 23e30.
4. Shi, Z.; Cui, Y.; Jiao, N. Angew. Chem., Int. Ed. 2010, 49, 4036e4041.
5. Burke, M. D.; Schreiber, S. L. Angew. Chem. 2004, 116, 48e60; Angew. Chem., Int.
Ed. 2004, 43, 46e58.
6. Mentel, M.; Schmidt, A. M.; Gorray, M.; Eilbracht, P.; Breinbauer, R. Angew.
Chem. 2009, 121, 5955e5958; Angew. Chem., Int. Ed. 2009, 48, 5841e5844.
7. Horton, D. A.; Bourne, G. T.; Smythe, M. L. Chem. Rev. 2003, 103, 893e930.
8. Walker, S. D.; Barder, T. E.; Martinelli, J. R.; Buchwald, S. L. Angew. Chem. 2004,
116, 1907e1912; Angew. Chem., Int. Ed. 2004, 43, 1871e1876.
9. Crystallographic data (excluding structure factors) for structure 6b has been
deposited with the Cambridge Crystallographic Data Centre as supplementary
publication CCDC-798317. Copies of the data can be obtained, free of charge, on
application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK, (fax: þ44 (0)1223
336033 or e-mail: deposit@ccdc.cam.ac.Uk).
4.5. Bromination of pyrrolo[3,2-b]quinolones general
procedure
A 25 mL round-bottom flask was charged consecutively with
1.0 equiv 7, 15 mL AcOH and 1.1 equiv N-bromosuccinimide. The
suspension was homogenized by immersing in an ultrasonic bath
under Ar atmosphere for 1 h. The solvent was evaporated in vacuo
and the residue suspended in 20 mL 5% aq Na2SO3 and homoge-
nized by immersing in an ultrasonic bath for 1 min. A solid was
collected by filtration through a sintered glass funnel and washed
with H2O until neutral reaction of the filtrate before dried under
high vacuum.
10. Reviews: (a) Haider, N.; Holzer, W. Sci. Synth. 2004, 16, 251e313; (b) Vinogra-
dova, O. V.; Balova, I. A. Chem. Heterocycl. Compd. 2008, 44, 501e522; Selected
original papers, regarding the structure of N-alkyl cinnolines: (c) Holzer, W.;
Eller, G. A.; Schoenberger, S. Heterocycles 2008, 75, 77e86; (d) Stanczak, A.;
Kwapiszewski, W.; Szadowska, A.; Pakulska, W. Pharmazie 1994, 49, 406e412;
(e) Ellis, A. W.; Lovesey, A. C. J. Chem. Soc. B 1968, 1393e1396; (f) Ames, D. E.;
Chapman, R. F.; Kucharska, H. Z.; Waite, D. J. Chem. Soc. 1965, 5391e5401.
11. Criegee, R. Angew. Chem. 1975, 21, 765e771; Angew. Chem., Int. Ed. Engl. 1975, 14,
745e752.
Compound 7a (0.184 g, 1.00 mmol) yield 0.195 g (0.741 mmol,
74%) 3-bromo-1H-pyrrolo[3,2-b]quinolin-9(4H)-one (9a) as a light-
brown solid. Mp 227e232 ꢀC; 1H NMR (400 MHz, DMSOd6):
€
12. (a) Boche, G.; Bosold, F.; Schroder, S. Angew. Chem. 1988, 100, 965e966; Angew.
Chem., Int. Ed. Engl. 1988, 27, 973e974; (b) Famulok, M.; Bosold, F.; Boche, G.
Angew. Chem. 1989, 101, 349e350; Angew. Chem., Int. Ed. Engl. 1989, 28,
337e338; (c) Famulok, M.; Bosold, F.; Boche, G. Tetrahedron Lett. 1989, 30,
321e324; (d) Ulbrich, R.; Famulok, M.; Bosold, F.; Boche, G. Tetrahedron Lett.
1990, 31, 1689e1692.
d
¼12.27 (s, 1H, NH), 11.51 (s, 1H, NH), 8.25 (dd, 3J¼8.1 Hz, 4J¼1.1 Hz,
1H, 8-H), 7.77 (d, 3J¼8.3 Hz, 1H, 5-H), 7.61 (overlaid ddd, 3J¼8.4,
7.0 Hz, 4J¼1.5 Hz, 1H, 6-H), 7.58 (overlaid d, 3J¼3.2 Hz, 1H, 2-H), 7.21
(ddd, 3J¼7.9, 7.0 Hz, 4J¼1.0 Hz, 1H, 7-H), 6.21 (dd, 3J¼2.4 Hz,
13. Raschig, F. Ber. Deut. Chem. Ges. 1907, 40, 4580e4588.
14. Nickon, A.; Sinz, A. J. Am. Chem. Soc. 1960, 82, 753e754.
ꢁ
15. (a) Kocienski, P. J. Protecting Groups, 3rd ed.; Georg Thieme: Stuttgart, 2005; (b)
4J¼2.4 Hz, 1H, 3-H); 13C NMR (100 MHz, DMSOd6, APT):
¼166.2
d
Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic Synthesis, 3rd ed.; John
Wiley & Sons: 1999.
16. Deng, X.; Mani, N. S. Green Chem. 2006, 8, 835e838.
17. Bailey, A. S.; Birch, C. M.; Illingworth, D.; Willmott, J. C. J. Chem. Soc., Perkin Trans.
1 1978, 1471e1476.
(Cq, C]O), 139.9 (Cq, CAr), 133.4 (Cq, CAr), 130.8 (CH, CAr), 127.3 (CH,
CAr), 125.3 (CH, CAr), 121.9 (Cq, CAr), 120.2 (CH, CAr), 119.8 (Cq, CAr),
117.6 (CH, CAr), 80.5 (Cq, C-3); HRMS (MeOH, ESIþ): m/z: calcd for