One-Pot, Three-Component Synthesis of Novel Pyrroloacridinones via Intramolecular ipso Dearomatization-Intramolecular Aza-Michael Addition Sequence

Article abstract of DOI:10.1055/s-0034-1379228

A one-pot, three-component synthesis of novel pyrroloacridinones from a set of alkoxy arenes and 2,6-dialkylphenols, isobutyric aldehyde, and 2-aminobenzonitrile is described. We have demonstrated the efficacy of the combination of intramolecular electrop

Full text of DOI:10.1055/s-0034-1379228

LETTER
▌2617
lOettenr e-Pot, Three-Component Synthesis of Novel Pyrroloacridinones via Intra-
molecular ipso Dearomatization–Intramolecular Aza-Michael Addition
Sequence
Synthesis of Novel Pyrroloacridinones
a
a
a
a
b
Yuliya S. Rozhkova,* Kristina A. Galata, Alexey A. Gorbunov, Yurii V. Shklyaev, Marina A. Ezhikova,
Mikhail I. Kodess
b
a
Institute of Technical Chemistry, Ural Branch of Russian Academy of Sciences, 13 Akademika Koroleva St., 614107, Perm,
Russian Federation
Fax +7(342)2378262; E-mail: rjs@mail.ru
b
Postovsky Institute of Organic Synthesis, Ural Branch of Russian Academy of Sciences, 22/20 S. Kovalevskoy/Akademicheskaya St.,
20990, Yekaterinburg, Russian Federation
6
Received: 09.07.2014; Accepted after revision: 10.09.2014
of 2-azaspiro[4.5]deca-1,6,9-trien-8-ones via a three-
component condensation of a set of alkoxy arenes and al-
Abstract: A one-pot, three-component synthesis of novel pyrro-
loacridinones from a set of alkoxy arenes and 2,6-dialkylphenols,
isobutyric aldehyde, and 2-aminobenzonitrile is described. We have
kylphenols with isobutyric aldehyde and nitrile in the
5
demonstrated the efficacy of the combination of intramolecular presence of concentrated sulfuric acid (Scheme 1). This
electrophilic ipso dearomatization of suitable aromatic compounds method is based on the intramolecular electrophilic ipso
leading to spiro-substituted cyclohexa-2,5-dienones and intramo-
lecular aza-Michael addition for the preparation of complex aza-
heterocyclic systems.
dearomatization of suitable aromatic compounds. Since
the 2-azaspiro[4.5]deca-1,6,9-trien-8-ones could be suit-
able substrates for the 1,4-conjugate addition, we asked
ourselves whether ipso intramolecular dearomatization–
intramolecular aza-Michael addition sequence would be
observed if nitrile containing an additional amino group
Key words: intramolecular ipso dearomatization, spiro-substituted
cyclohexa-2,5-dienone, intramolecular aza-Michael addition, dom-
ino reaction, cyclization
were used.
Dearomatization of para-substituted phenols and alkoxy
arenes forming 4,4-disubstituted-cyclohexa-2,5-dien-
OX
R1
O
H2SO4
ones, coupled with intramolecular 1,4-conjugate addition
is an efficient and convenient synthetic approach to differ-
ent carbo- and heterocyclic-fused ring systems with a
cyclohexenone moiety, including bioactive compounds
R1
+
O
N
H
R2
2
R CN
1
–3
Scheme 1 Formation of 2-azaspiro[4.5]deca-1,6,9-trien-8-ones via a
three-component condensation
and structural units found in natural products.
Combination of intramolecular ipso dearomatization of
arenes leading to spiro-substituted cyclohexa-2,5-dien-
ones and intramolecular 1,4-conjugate addition is of par-
ticular interest because this synthetic transformation
provides a facile route to the construction of highly func-
tionalized fused spiro tricyclic or tetracyclic compounds
To estimate a possibility of this transformation, we inves-
tigated the condensation of various alkoxy arenes and 2,6-
dialkylphenols 1 with isobutyric aldehyde 2 and 2-amino-
benzonitrile 3. Our investigation started with the reaction
of 1-methoxynaphthalene (1a) with isobutyric aldehyde
4
with a quaternary carbon at the ring-fused position. Fur-
thermore, in some cases this process leads to the forma-
(2) and 2-aminobenzonitrile (3) in the presence of concen-
trated sulfuric acid.
tion of structures bearing an asymmetric quaternary
carbon center.4 Despite great potential of this synthetic We were pleased to find that the desired intramolecular
d–g
approach to the construction of complex heterocyclic sys- ipso dearomatization–intramolecular aza-Michael addi-
tems, its use is currently limited.
tion domino sequence had occurred, and novel tetrahydro-
benzo[a]pyrrolo[2,3-m]acridin-5(6H)-one (5a) was
isolated in 82% yield as a single diastereomer (Scheme 2,
Here, we demonstrated an efficient route to novel pyrro-
loacridinones via a one-pot, three-component protocol via
intramolecular ipso dearomatization–intramolecular aza-
Michael addition sequence. We have recently developed a
simple and efficient one-pot protocol for the construction
6
,7
Table 1, entry 1). The stereochemistry of 5a was clearly
1
1
determined by a 2D H– H NOESY experiment (Figure
).
1
SYNLETT 2014, 25, 2617–2623
Advanced online publication: 15.10.2014
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
DOI: 10.1055/s-0034-1379228; Art ID: st-2014-b0574-l
Georg Thieme Verlag Stuttgart · New York
©

2618
Yu. S. Rozhkova et al.
LETTER
OMe
Next, we investigated the scope of the reaction. This pro-
tocol was applied to a set of alkoxy arenes and 2,6-di-
alkylphenols 1b–j to produce the corresponding
pyrroloacridinones 5b–j. The results are summarized in
Table 1.
O
H
N
H2SO4
1a
2
CN
5
°C to r.t.
25 min
NH2
O
N
H
In the case of anisole 1b, the domino reaction had led to
pyrroloacridinone 5b as a single diastereomer in 40% iso-
lated yield (Table 1, entry 2). 2-Methylanisole (1c), 1,2,3-
trimethoxy- and 1,2-dimethoxy-4-methylbenzenes 1d,e
H
(
± ±)5a, 82%
3
Scheme 2 Synthesis of tetrahydrobenzo[a]pyrrolo[2,3-m]acridin- provided the products 5c–e in 73%, 44%, and 55% yields,
5(6H)-one (5a)
respectively (Table 1, entries 3–5). 4-Isopropyl-2-me-
thoxy-1-methylbenzene (1f) afforded pyrroloacridinone
5
1
f along with the intermediate spiro compound 4f (Table
, entry 6). Both compounds could be efficiently separat-
HB
HA
H
Me
Me
ed by column chromatography in 53% and 9% yield, re-
spectively. In an attempt to obtain 5f as a sole product, a
reaction time was examined. Although the prolongation of
the reaction time to four hours led to disappearance of 4f
O
N
H
H
HN
(monitored by TLC and GC–MS analysis), significant
Figure 1 Key NOE connectivities for (±)-tetrahydrobenzo[a]pyrro- resinification was observed after neutralization of the re-
lo[2,3-m]acridin-5(6H)-one (5a)
action mixture. In addition, the yield of 5f decreased to
6% probably due to sulfonation. It is worth noting that
treatment of 4f with H SO resulted in the formation of
pyrroloacridinone 5f. This result had supported the pro-
posed mechanism for the formation of pyrroloacridinones
3
A plausible mechanism for the formation of 5a is outlined
in Scheme 3. The reaction begins with the protonation of
isobutyric aldehyde 2 which, in turn, alkylates 1-me-
thoxynaphthalene (1a) at the para position of the methoxy
group to give the benzylic carbocation A, which then re-
arranges to the tertiary carbocation A′. The carbocationic
intermediate A′ reacts with 2-aminobenzonitrile (3) in the
fashion of the Ritter reaction to form a nitrilium ion B.
Subsequent intramolecular electrophilic ipso cyclization
of nitrilium ion B affords a spiro-σ-complex C. Trapping
of the intermediate C by water and subsequent loss of
MeOH led to protonated intermediate spiro compound 4a.
Finally, 4a undergoes the intramolecular aza-Michael ad-
dition to provide pyrroloacridinone 5a.
2
4
5
through the acid-catalyzed intramolecular aza-Michael
addition of spirocyclohexadienones 4. Three-component
condensation with 2-methoxy-1,4-dimethylbenzene (1g),
as well as with 1f, led to pyrroloacridinone 5g along with
spiro compound 4g in 63% and 11% yield, respectively.
Importantly, pyrroloacridinones 5b–g were obtained as
single regio- and diastereomers. The initially formed spi-
rocyclohexadienones 4c–g underwent the regioselective
intramolecular aza-Michael addition. Nucleophilic attack
by an NH2
group on the cyclohexadienone fragment of
OMe
OMe
OMe
OMe
+
O
H
H+
OH
OH
+
1
a
– H2O, – H+
H
H
2
N
NH2
+
+
A
B
A'
+
NH2
•
•
– H+
CN
3
+
OH
+
OMe
H2O OMe
H2O
+
•
•
5a
NH2
–
H+
– MeOH
N
N
N
2
H N
H2N
4
a)H+
D
C
Scheme 3 Proposed reaction mechanism for the formation of pyrroloacridinone 5a
Synlett 2014, 25, 2617–2623
© Georg Thieme Verlag Stuttgart · New York

LETTER
Synthesis of Novel Pyrroloacridinones
2619
4
c–g was more favored at C-10 of 4c,d and at C-6 of 4e– and is in agreement with the previously reported re-
3
k,4c,8,9
g, respectively (Scheme 4). The regioselectivity of the sults.
aza-Michael addition may be caused by electronic factors
Table 1 Scope of the Three-Component Condensation for Preparation of Pyrroloacridinones 5a
R1
OX
CN
N
O
R1
NH2
O
H
H SO
2 4
H SO
2
4
R1
N
+
+
O
N
H
R2
NH2
1
2
3
X = H, Me
R1 = Me, OMe
4
(± ±)5 R2 = H, Me
Entry Arene 1
Product 4
Yield (%)b Product 5
Yield (%)b
OMe
N
O
N
1
0
82
NH2
O
N
H
H
1
a
(
±)-5a
4
a
OMe
N
O
N
2
3
0
0
40c
NH2
O
N
H
H
1
1
b
4
b
(±)-5b
OMe
N
O
N
73
NH2
O
N
H
H
c
(
±)-5c
4
c
MeO
OMe
OMe
N
N
MeO
O
MeO
OMe
N
MeO
O
4
0
44c
NH2
H
H
1
d
(
±)-5d
4
d
OMe
N
OMe
O
N
MeO
O
5
MeO
0
55c
NH2
N
H
1
e
(
±)-5e
4
e
©
Georg Thieme Verlag Stuttgart · New York
Synlett 2014, 25, 2617–2623

2620
Yu. S. Rozhkova et al.
LETTER
a
Table 1 Scope of the Three-Component Condensation for Preparation of Pyrroloacridinones 5 (continued)
R1
OX
CN
N
O
R1
NH2
O
H
H SO
2 4
H SO
2
4
R1
N
+
+
O
N
H
R2
NH2
1
2
3
X = H, Me
R1 = Me, OMe
4
(± ±)5 R2 = H, Me
Entry Arene 1
Product 4
Yield (%)b Product 5
Yield (%)b
OMe
N
O
N
i)Pr
i)Pr
6
9
53
i)Pr
NH2
O
N
H
1
f
(
±)-5f
4
f
OMe
N
O
N
7
11
63
NH2
O
N
H
1
g
(
±)-5g
4
g
N
N
OH
O
N
+
8
tracesd
66d
O
N
H
O
N
H
NH2
H
H
1
h
(
(
±)-5h + (±)-5h′
84:16)
4
h
i)Pr
N
N
OH
O
i)Pr
i)Pr
i)Pr
i)Pr
N
+
9
22
44e
i)Pr
O
N
O
N
H
NH2
H
H
H
i)Pr
i)Pr
1
i
(
(
±)-5i + (±)-5i′
25:75)
4
i
t)Bu
N
OH
O
t)Bu
t)Bu
t)Bu
N
10
5
6c
t)Bu
NH2
O
N
H
H
t)Bu
1
j
4
j
(±)-5j′
a
Reaction conditions: arene 1 (2.0 mmol), isobutyric aldehyde (2, 3.0 mmol), 2-aminobenzonitrile (3, 2.0 mmol), H SO (92%, 1 mL, 17
2
4
mmol), 5 °C to r.t., 25 min. See Supporting Information for details.
b
Isolated yield.
c
Starting 2-aminobenzonitrile was recovered for 1b, 30%; for 1d, 38%; for 1e, 33%; for 1j, 22%.
d
GC–MS analysis of the crude reaction mixture revealed the presence of trace amount of spiro cyclohexadienone 4g.
e
1
Combined yields of diastereomers. The diastereomeric ratio was determined by H NMR analysis.
Synlett 2014, 25, 2617–2623
© Georg Thieme Verlag Stuttgart · New York

LETTER
Synthesis of Novel Pyrroloacridinones
2621
R1
observe correlations between these protons, but there
were cross-peaks between protons H-3AB and protons of
the isopropyl group at C-7. This indicates a pseudoaxial
orientation of the isopropyl group at C-7 in the compound
5i′. Furthermore, the structures of diastereomers 5h and 5i
were unambiguously confirmed by X-ray diffraction anal-
R2
R2
O
7
6
0
9
8
7
8
4
O
10
6
4
5
1
3
3
9
5
1
2
2
1
H+
N
H+
N
5
e–g
5c,d
•
•
R1
•
•
H2N
H2N
1
0
ysis (ORTEP drawing of 5h see Figure 4).
4
c, d
4
e–g
c: R1 = Me, R = H
2
4e: R = Me, R = OMe
1
2
4
4
d: R1 = R = OMe
2
4f: R = R = Me
1
2
HB
A
HB
HA
g: R1 = Me, R = i-Pr
2
4
H
Me
Me
H
R
Me
Me
R
R
6
3
6
3
2
5
4
7a
2
5
4
3a
7
3a
1
Scheme 4
O
7
1
O
7a
N
N
R
H
1
2b
12b
12a
H
H
HN8
8a
12a
HN8
1
2
12
With 2,6-dimethyl- and 2,6-diisopropylphenols 1h,i the
pyrroloacridinones were obtained as a mixture of diaste-
reomers 5h/5h′ and 5i/5i′ in 66% and 44% combined
yields, respectively (Table 1, entries 8 and 9). The diaste-
reoselectivity ranged from 84:16 (Table 1, entry 8) to
8a
9
11
9
11
10
10
(± ±-5h R = Me
(± ±-5i' R = i-Pr
(± ±-5i R = i-Pr
Figure 3 Determination of stereochemistry of 5h,i,i′. Key NOE con-
nectivities.
25:75 (Table 1, entry 9). Attempts to separate the diaste-
reomers 5h/5h′ by column chromatography were unsuc-
cessful, but the major isomer 5h was isolated as an
individual compound by recrystallization of the mixture
5h/5h′. The diastereomers 5i/5i′ were separated by col-
umn chromatography. For the reaction with 2,6-dimethyl-
phenol (1h), trace amount of spirocyclohexadienone 4h
was observed. In the case with 2,6-diisopropylphenol (1i),
an intermediate spiro compound 4i was also isolated in
2
2% yield. The structure of the product 4i was confirmed
1
0
by X-ray diffraction analysis (Figure 2).
Figure 4 ORTEP drawing of (±)-5h10
Three-component synthesis with 2,6-di-tert-butylphenol
(1j) led to a complex mixture of the products. GC–MS
analysis of the crude reaction mixture revealed the pres-
ence of products of de-tert-butylation and rearrangement
of the 2,6-di-tert-butylphenol (1j). These reactions are
1
1
typical for tert-butylbenzenes in acidic media. In this
case, chromatographic separation of the reaction mixture
afforded only 6% of pyrroloacridinone 5j′ along with 5%
of spiro compound 4j and 22% of starting 2-aminobenzo-
nitrile (3) (Table 1, entry 10). The structure of 5j′ was con-
1
0
firmed by X-ray analysis.
In an attempt to obtain pyrroloacridinone 5j′ in good
yield, reaction of 2,6-di-tert-butyl-4-(1-hydroxy-2-meth-
ylpropyl)phenol (6) with 2-aminobenzonitrile (3) was
studied. In this case product 5j′ was obtained in 41%
yield, together with spiro compound 4j and compound 7
Figure 2 ORTEP drawing of 4i10
The relative configuration of the products 5h, 5i, and 5i′
1
1
was initially assigned by 2D H– H NOESY experiments
Figure 3). In the case with compounds 5h and 5i NOE
1
in 13% and 7% yields, respectively (Scheme 5). 2D H–
(
1
H NOESY experiments showed the minor product 7 to
connectivities between proton H-7 and nonequivalent
protons H-3A and H-3B of the pyrrole fragment revealed
that the alkyl groups at C-7 were in a pseudoequatorial
orientation. In NOESY spectrum of isomer 5i′ we did not
have the same relative configuration as 5j′. Formation of
7 may be accounted for by the tert-butylation of starting
2-aminobenzonitrile (3), of intermediate spiro compound
4j or of pyrroloacridinone 5j′ during the course of the re-
©
Georg Thieme Verlag Stuttgart · New York
Synlett 2014, 25, 2617–2623

2622
Yu. S. Rozhkova et al.
LETTER
action. In this case, carbinol 6 or an intermediate spiro-
σ-complex may be assumed to act as a tert-butyl cation
source.
A. Org. Lett. 2007, 9, 5019. (g) Gu, Q.; Rong, Z.-Q.; Zheng,
C.; You, S.-L. J. Am. Chem. Soc. 2010, 132, 4056. (h) Liu,
Q.; Rovis, T. J. Am. Chem. Soc. 2012, 128, 2552. (i) Jia,
M.-Q.; You, S.-L. Synlett 2013, 24, 1201. (j) Ratnikov, M.
O.; Farkas, L. E.; Doyle, M. P. J. Org. Chem. 2012, 77,
OH
4j, 13%
5j', 41%
1
0294. (k) Tello-Aburto, R.; Kalstabakken, K. A.; Volp, K.
+
t-Bu
t-Bu
A.; Harned, A. M. Org. Biomol. Chem. 2011, 9, 7849.
(4) (a) Node, M.; Kodama, S.; Hamashima, Y.; Baba, T.;
Hamamichi, N.; Nishide, K. Angew. Chem. Int. Ed. 2001, 40,
3060. (b) Canesi, S.; Bouchu, D.; Ciufolini, M. A. Angew.
Chem. Int. Ed. 2004, 43, 4336. (c) Santra, S.; Andreana, P.
R. Angew. Chem. Int. Ed. 2011, 50, 9418. (d) Leon, R.;
Jawalekar, A.; Redert, T. M.; Gaunt, J. Chem. Sci. 2011,
H2SO4
+
3
N
5
°C to r.t.
2
5 min
t-Bu
t-Bu
HO
O
N
H
6
H
t-Bu
1
487. (e) Rodríguez-Solla, H.; Concellón, C.; Tuya, P.;
García-Granda, S.; Dίaz, M. R. Adv. Synth. Catal. 2012, 354,
95. (f) Kodama, S.; Hamashima, Y.; Nishide, K.; Node, M.
(
± ±-7, 7%
2
Scheme 5
Angew. Chem. Int. Ed. 2004, 43, 2659. (g) Jia, M. Q.; You,
S. L. Chem. Commun. 2012, 48, 6363.
In conclusion, we have developed a simple and efficient
one-pot, three-component domino protocol to prepare
novel pyrroloacridinones via intramolecular ipso dearo-
matization–intramolecular aza-Michael addition domino
sequence. This approach provides a facile route to the
complex aza-heterocyclic structures from readily avail-
able starting materials. Further studies of potential scope
and synthetic applications of this reaction are in progress
in our laboratory.
(5) (a) Nifontov, Y. V.; Glushkov, V. A.; Ausheva, O. G.;
Shklyaev, Y. V. Russ. J. Org. Chem. 2002, 38, 1386.
(
b) Nifontov, Y. V.; Glushkov, V. A.; Shklyaev, Y. V. Russ.
Chem. Bull. 2003, 52, 437. (c) Glushkov, V. A.;
Stryapunina, O. G.; Gorbunov, A. A.; Mayorova, O. A.;
Slepukhin, P. A.; Ryabukhina, S. Y.; Khorosheva, E. V.;
Sokol, V. I.; Shklyaev, Y. V. Tetrahedron 2010, 66, 721.
(d) Rozhkova, Y. S.; Khmelevskaya, K. A.; Shklyaev, Y. V.;
Ezhikova, M. A.; Kodess, M. I. Russ. J. Org. Chem. 2012,
48, 69. (e) Rozhkova, Y. S.; Galata, K. A.; Vshivkova, T. S.;
Shklyaev, Y. V. Chem. Heterocycl. Compd. 2014, 50, 204.
6) Typical Experimental Procedure for the Synthesis of 5a
A mixture of 1-methoxynaphthalene (1a, 316 mg, 2.0
mmol), isobutyric aldehyde (2, 216 mg, 3.0 mmol), and
(
Acknowledgment
This work was financially supported by the Russian Foundation of
Basic Research (No11-03-00367, No 13-03-00184).
2
-aminobenzonitrile (3, 236 mg, 2.0 mmol) was added
dropwise to stirred concentrated sulfuric acid (92%, 1 mL,
7 mmol) at 5–7 °C. The reaction mixture was stirred at r.t.
1
for 25 min and poured into a mixture of ice (25 g) and aq
NH (7 mL). The product was extracted with CH Cl (3 × 15
Supporting Information for this article is available online
3
2
2
at
http://www.thieme-connect.com/products/ejournals/journal/
mL), and the combined organic layers were washed with
H O, dried over anhydrous Na SO , and filtered. After the
1
0.1055/s-00000083.SunpfgIpi
o
nr
i
o
2
2
4
solvent was removed, the crude mixture was purified by
column chromatography on silica gel (hexane–EtOAc, 4:1 to
References and Notes
2:1) to give pure 5a (516 mg, 82%).
(
1) For selected reviews, see: (a) Ding, Q.; Ye, Y.; Fan, R.
Synthesis 2013, 45, 1. (b) Dalpozzo, R.; Bartoli, G.;
Bencivenni, G. Symmetry 2011, 3, 84.
(
7) Data for 5a
Pale yellow solid; R = 0.63 (hexane–EtOAc, 2:1); mp 267–
f
2
69 °C. IR (film): ν = 3364, 3066, 3026, 2964, 2867, 1674,
(2) (a) Schwartz, M. A.; Hudec, T. T. Synth. Commun. 1986, 16,
–1 1
1610 cm . H NMR (500 MHz, CDCl ): δ = 1.42 (s, 3 H,
3
1599. (b) Wipf, P.; Kim, Y. Tetrahedron Lett. 1992, 33,
13
13
CH C ), 1.47 (s, 3 H, CH C ), 2.05 (d, 1 H, J = 13.1 Hz, H-
3
B
3
5477. (c) Redondo, M. C.; Ribagorda, M.; Carreño, M. C.
A
1
1
3
4 ), 2.10 (d, 1 H, J = 13.1 Hz, H-14 ), 2.79 (dd, 1 Н, J =
8.0, 3.0 Hz, H-6 ), 3.02 (dd, 1 Н, J = 18.0, 3.0 Hz, H-6 ),
.96 (t, 1 H, J = 3.0 Hz, H-6a), 4.32 (br s, 1 H, NH), 6.41 (br
Org. Lett. 2010, 12, 56. (d) Glushkov, V. A.; Krainova, G.
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B
A
d, 1 H, J = 8.3 Hz, H-8), 6.72 (ddd, 1 H, J = 7.9, 7.1, 1.2 Hz,
H-10), 7.06–7.10 (m, 2 H, H-1 and H-9), 7.29 (td, 1 H, J =
(e) Carreño, M. C.; González-López, M.; Urbano, A. Angew.
Chem. Int. Ed. 2006, 45, 2737. (f) Tohma, H.; Harayama, Y.;
Hashizume, M.; Iwata, M.; Egi, M.; Kita, Y. Angew. Chem.
Int. Ed. 2002, 41, 348. (g) Cha, J. Y.; Burnett, G. L. IV.;
Huang, Y.; Davidson, J. B.; Pettus, T. R. R. J. Org. Chem.
7
.6, 1.0 Hz, H-3), 7.41 (td, 1 H, J = 7.6, 1.4 Hz, H-2), 7.92
(dd, 1 H, J = 7.9, 1.5 Hz, H-11), 8.03 (dd, 1 H, J = 7.8, 1.4
13
Hz, H-4) ppm. C NMR (75 MHz, CDCl ): δ = 29.29
3
13
13
(
(
(
(
(
CH C ), 32.46 (CH C ), 40.53, 48.41 (C-6, C-14), 56.30
3
3
2
011, 76, 1361. (h) Martin, S. F.; Davidsen, S. K.; Puckette,
C-14a), 58.45 (C-6a), 72.87 (C-13), 114.75 (C-8), 115.62
C-11a), 118.32 (C-10), 126.85, 127.00, 127.31 and 127.90
C-1, C-4, C-9, and C-11), 131.08 (C-4a), 131.81 and 134.17
T. J. Org. Chem. 1987, 52, 1962.
(
3) For enantioselective desymmetrization Michael addition of
4,4-disubstituted cyclohexa-2,5-dienones, see: (a) Hayashi,
C-2, C-3), 143.59 and 147.00 (C-7a and C-14b), 166.59 (C-
Y.; Gotoh, H.; Tamura, T.; Yamaguchi, H.; Masui, R.; Shoji,
M. J. Am. Chem. Soc. 2005, 127, 16028. (b) Gu, Q.; You,
S.-L. Chem. Sci. 2011, 2, 1519. (c) Gu, Q.; You, S. Org. Lett.
+
1
1b), 195.23 (С-5). MS (EI): m/z (%) = 316 [M] (78), 316
+
[M – Me] (100). Anal. Calcd for C H N O: C, 79.72; H,
21 20 2
6
.37; N, 8.85. Found: C, 79.42; H, 6.43; N, 8.64..
2
011, 13, 5192. (d) Vo, N. T.; Pace, R. D. M.; O’Hara, F.;
(
8) Ciufolini, M. A.; Dong, Q.; Yates, M. H.; Schunk, S.
Tetrahedron Lett. 1996, 37, 2881.
9) Giomi, D.; Piacenti, M.; Brandi, A. Eur. J. Org. Chem. 2005,
Gaunt, M. J. J. Am. Chem. Soc. 2008, 130, 404. (e) Rubush,
D. M.; Morges, M. A.; Rose, B. J.; Thamm, D. H.; Rovis, T.
J. Am. Chem. Soc. 2012, 134, 13554. (f) Barradas, S.;
Carreño, M. C.; González-López, M.; Latorre, A.; Urbano,
(
2
1, 4649.
Synlett 2014, 25, 2617–2623
© Georg Thieme Verlag Stuttgart · New York

LETTER
Synthesis of Novel Pyrroloacridinones
2623
(
10) Crystallographic data for compound 4i, 5h, 5i′, and 5j' have
been deposited with the Cambridge Crystallographic Data
Centre [CCDC no 988501 (4i), CCDC no 988502 (5h),
CCDC no 988503 (5i'), CCDC no 988504 (5j')]. These data
can be obtained free of charge from the Cambridge
Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif. See Supporting
Information for details.
(11) (a) Smith, M. B.; March, J. March's Advanced Organic
Chemistry: Reactions, Mechanisms and Structure; John
Wiley and Sons: Hoboken, 2007, 6th ed., 742. (b) Bruckner,
R. Organic Mechanisms: Reactions, Stereochemistry and
Synthesis; Springer: Berlin/Heidelberg, 2010, 205.
©
Georg Thieme Verlag Stuttgart · New York
Synlett 2014, 25, 2617–2623

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