Stereoselective tandem synthesis of oxazolo-fused pyrroloquinolines from o-alkynylaldehydes via Ag(I)-catalyzed regioselective 5-exo-dig ring closure

Article abstract of DOI:10.1016/j.tetlet.2014.02.103

A tandem approach for the regio- and stereoselective synthesis of oxazolo-fused pyrroloquinolines 3a-l via the reaction of o-alkynylaldehydes 1a-i with chiral amino alcohols 2a-c under mild reaction conditions is described. The possible participation of the pyridine ring in the regioselective formation of 5-exo-dig cyclized products was supported by the controlled experiments. The structures and stereochemistry of the products were confirmed by NOESY and X-ray crystallographic studies.

Full text of DOI:10.1016/j.tetlet.2014.02.103

Tetrahedron Letters 55 (2014) 2603–2608
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Stereoselective tandem synthesis of oxazolo-fused pyrroloquinolines
from o-alkynylaldehydes via Ag(I)-catalyzed regioselective 5-exo-dig
ring closure
⇑
Rajeev Ranjan Jha, Trapti Aggarwal, Akhilesh Kumar Verma
Department of Chemistry, University of Delhi, Delhi 110007, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A tandem approach for the regio- and stereoselective synthesis of oxazolo-fused pyrroloquinolines 3a–l
via the reaction of o-alkynylaldehydes 1a–i with chiral amino alcohols 2a–c under mild reaction condi-
tions is described. The possible participation of the pyridine ring in the regioselective formation of 5-exo-
dig cyclized products was supported by the controlled experiments. The structures and stereochemistry
of the products were confirmed by NOESY and X-ray crystallographic studies.
Received 27 December 2013
Revised 19 February 2014
Accepted 23 February 2014
Available online 5 March 2014
Ó 2014 Elsevier Ltd. All rights reserved.
Keywords:
Tandem cyclization
Oxazole
Pyrrolo-quinolines
Stereoselective
Silver
Numerous heterocycles are structural components of biologi-
cally active natural and non-natural compounds.1 Furthermore,
optically active N-heterocyclic compounds are used in asymmetric
fusion as chiral templates2 or ligands.3 From the past two decades,
the synthesis of solitary stereoisomers has been in continuous
demand.
complex molecules from simple starting materials in an iterative
manner. Silver-catalyzed cyclizations,11 have acquired incredible
success due to their cost and capability to trigger alkynes and al-
kenes toward cyclization.
By considering the features of our recent synthesis of
oxazolo and thiazolo fused naphthyridine from o-alkynylaldehy-
des (Scheme 1)12 and application of o-alkynylaldehydes as a
building blocks in the synthesis of variety of heterocyclic
scaffolds,13 herein for the first time we report the synthesis of
oxazolo fused pyrroloquinolines via 5-exo-dig ring closure using
AgOTf (Scheme 2).
The motive for developing optically pure diastereomers and dis-
tinct compounds is due to their divergent biological activity, as dis-
played in numerous cases by each diastereomer of an optically
active compound.4 Among these benzoxazole, an aromatic
member of nitrogen and oxygen family, appears in many bioactive
naturally-occurring compounds.5 The importance of these hetero-
cyclic derivatives justifies the continuous endeavors to develop a
new one-pot synthetic strategy for the synthesis of oxazole deriv-
atives.6,7 Literature survey revealed that till now there are no re-
ports on the synthesis of oxazolo-fused-pyrroloquinolines.
From the past decade, metal-catalyzed reactions became recog-
nized for the synthesis of carbocyclic compounds and natural-
product-like scaffolds because of their high reactivity, tolerance to-
ward various functional groups, and excellent ability to activate
CHO
Ar
HS
ClHH2.
HO
ClHH2.N
H
R1
H
N
COOMe
COOMe
AuCl3 (10 mol %)
6-endo-dig cyclization
the
p
-systems toward CAC and CAN bond formations.8 Among
S
H
O
H
H
H
these reactions, tandem cyclization9,10 using silver has received a
significant interest as these reactions can swiftly synthesize the
COOMe
COOMe
N
N
Ar
Ar
R1
R1
Scheme 1. Previous work of our laboratory using o-alkynylaldehydes for the
synthesis of 6-endo-dig cyclized product.
⇑
Corresponding author.
E-mail address: averma@acbr.du.ac.in (A.K. Verma).
http://dx.doi.org/10.1016/j.tetlet.2014.02.103
0040-4039/Ó 2014 Elsevier Ltd. All rights reserved.

2604
R. R. Jha et al. / Tetrahedron Letters 55 (2014) 2603–2608
R4
H
H
O
N
i. Et3N (1.1 equiv)
ii. AgOTf (10 mol %)
CHO
HO
ClH.H2N
R4
H
R1
R1
+
R3
R2
R3
N
3a_l
N
1a_i
EtOH, 3-4 h
R2
2a_c
5-exo dig
H
R1 = H, OMe; R2 = aryl, alkyl; R3 = COOMe, Ph; R4 = H, Me
Scheme 2. Designed approach for the regio- and stereoselective synthesis of fused-oxazolo-pyrroloquinolines.
To identify the optimal conditions for the reaction, a previously
reported catalyst, Ag(I),12 for cyclization was examined in the reac-
tion of o-alkynylaldehyde 1a with -serine methyl ester hydrochlo-
when the reaction was carried out at 50 °C (entry 14). However
lowering of the catalyst loading afforded the product 3a in 54%
yield (entry 15). AgOAc was found ineffective for the reaction.
Au(I) and Au(III) afforded the mixture of 5-exo-dig 3a and 6-
endo-dig 4a cyclized products (entries 17 and 18). Other salts such
as CuI, Cu(OTf)2, and InCl3 were found to be ineffective for the reac-
tion (entries 19–21). No product was obtained without catalyst
(entry 22).
L
ride 2a in the presence of 1.1 equiv of Et3N (Table 1). When
10 mol % of AgNO3 was used as a catalyst in CH2Cl2 at 25 °C for
2 h, a mixture of oxazolo-fused-pyrroloquinoline 3a (exo product),
and naphthyridine 4a (endo product) was obtained in 5% and 8%
yields, respectively (entry 1). Increase in the reaction time, temper-
ature, and catalyst loading did not significantly affect the yield of
the products (entries 2–4). However, use of AgOTf as catalyst affor-
ded the mixture of 3a (5-exo-dig) and 4a (6-endo-dig) cyclized
products in 55% and 33% yields, respectively (entries 5 and 6).
Use of water and methanol as solvent afforded the product 3a
regioselectively in 10% and 58% yield respectively (entries 7 and
8). It is interesting to note that use of AgOTf in ethanol afforded
the 5-exo-dig cyclized product 3a as a sole product in 75% yield
(entry 9). Increase in catalyst loading from 10 mol % to 15 mol %
does not significantly affect the yield of the product 3a (entry
11). The yield of the product 3a remained the same upon decreas-
ing the reaction time (entry 12); however a further decrease in the
reaction time (from 3 to 2 h) adversely affected the yield of the
product (entry 13). Lower yield of the product 3a was obtained
The use of L-serine methyl ester controlled the chirality of the
product and afforded the 5-exo-dig cyclized products with high
diastereoselectivity. The relative configurations of the new stereo-
genic center at Hb in products 3a, 3h were determined by NOESY
experiments.14,15 The 1H NMR spectra of 3a, and 3h show that Hb
appears at 6.35 and 6.25 ppm, as a singlet and that Ha appears at
4.00–3.97 ppm, 3.70–3.69 ppm, respectively, as a multiplet. No dis-
tinct NOE effect was observed between Hb and Ha in compound 3a.
This result suggests that Hb and Ha are located in trans orientation.
X-ray crystallographic studies of compounds 3h and 3l further con-
firmed the structure of the products and supported the assigned
stereochemistry (Fig. 1).16,17 Optical rotations of the compounds
3h and 3l recorded before X-ray and after X-ray crystallography
were found to be the same.
Table 1
Optimization of the reaction conditionsa
H
O
H
catalyst
CHO
O
N
H
COOMe
solvent
Et3N
HO
N
+
+
H
H
COOMe
N
1a
N
3a
N
R2
ClHH2.
N
COOMe
R2
2 = 4-Me-C6H4
R2
4a
2a
R
Entry
Solvent
Catalyst (mol %)
T (°C)
Time (h)
Yield (%)b
3a
4a
1
2
3
4
5
6
7
8
9
11
12
13
14
15
16
17
18
19
20
21
22
CH2Cl2
CH2Cl2
CH2Cl2
CHCl3
CHCl3
DCE
AgNO3/10
AgNO3/10
AgNO3/15
AgNO3/15
AgOTf /10
AgOTf/10
AgOTf/10
AgOTf/10
AgOTf/10
AgOTf/15
AgOTf/10
AgOTf/10
AgOTf/10
AgOTf/5
AgOAc/10
AuCl/10
AuCl3/10
CuI/10
Cu(OTf)2/10
InCl3/10
—
25
40
40
60
60
70
90
70
70
70
70
70
50
70
50
70
70
70
70
70
70
2.0
4.0
6.0
6.0
6.0
6.0
6.0
6.0
6.0
6.0
3.0
2.0
3.0
3.0
3.0
3.0
3.0
3.0
3.0
3.0
3.0
08
12
18
21
55
55
10
58
75
75
75
61
49
54
37
17
25
10
23
5
05
09
15
17
33
40
00
00
00
00
00
00
00
00
12
32
62
00
45
18
00
H2O
MeOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
00
Bold value indicates the best reaction condition.
a
Reactions were performed using 0.6 mmol of 2a, 0.5 mmol of 1a and 0.6 mmol of NEt3 in 2.0 mL solvent. DCE = 1,2 dichloroethane.
Isolated yield.
b

R. R. Jha et al. / Tetrahedron Letters 55 (2014) 2603–2608
2605
no nOe
Hy
no nOe
Hy
Hx
bH
O
bH
O
(A)
Me
Ha
nOe
nOe
Ha
COOMe
N
N
COOMe
N
N
NOESY
3a
(S, S isomer)
cH
3h
cH
Me
Me
(S, R, S isomer)
zH
zH
nOe
nOe
O1
C5
C19
C20
C7
C25
C24
C18
C6
C26
C21
C8
C9
C4
C23
C22
N2
C1
C3
C10
(B)
C2
N1
C11
C12
C13
C14
C15
C17
C16
3h (5-exo-dig)
3l (5-exo-dig)
Figure 1. (A) NOESY interactions of 3h and 3a. (B) ORTEP drawings of 3h and 3l.
Table 2
Silver-catalyzed diastereoselective synthesis of 5-exo-dig oxazolo-fused pyrroloquinolinesa
Entry
Substrate
Amine
HO
Product
Yield (%)b
CHO
H
O
H
H
N
N
HCl.H2N
COOMe
COOMe
N
N
2a
1
75
76
Me
H
Me
1a
3a
H O
CHO
H
N
COOMe
N
2
2a
H
OMe
OMe
3b
1b
CHO
H O
H
N
COOMe
N
N
3
4
5
2a
2a
2a
77
72
68
H
Et
Et
3c
H O
1c
CHO
H
N
COOMe
N
N
N
H
3d
H
S
S
1d
CHO
O
H
N
COOM
N
H
3e
1e
CHO
H O
H
N
COOMe
N
c
N
6
2a
—
H
NO2
NO2
3f
1f
(continued on next page)

2606
R. R. Jha et al. / Tetrahedron Letters 55 (2014) 2603–2608
Table 2 (continued)
Entry
Substrate
Amine
Product
MeO
Yield (%)b
MeO
CHO
H O
H
N
COOMe
N
N
H
7
8
2a
72
H
1g
3g
HO
HCl.H2N
Me
H
COOMe
Me
O
H
N
COOMe
1a
78
N
2b
H
Me
3h
Me
H
O
H
N
COOMe
9
10
11
1e
2b
2b
70
N
H
3i
CHO
Me
H
O
H
N
N
COOMe
65
N
H
3j
1h
HO
H
O
H
Ph
N
H2N
H
1a
75d
2c
N
H
Me
3k
H
O
N
H
12
1e
2c
72d
N
H
3l
a
Reactions were performed using 0.5 mmol of 1, 1.1 equiv of 2, 1.1 equiv of Et3N, 10 mol % AgOTf in 2.0 mL of EtOH at 70 °C for 3–4 h.
Isolated yield.
Inseparable complex mixture.
Using without Et3N.
b
c
d
Having determined the optimal conditions (Table 1, entry 12),
To validate the possible participation of the pyridine ring in the
regioselective formation of 5-exo-dig cyclized products, we carried
out a controlled experiment, which involved the reaction of alkyne
1i with phenyl glycinol 2c under optimized reaction conditions
(Scheme 3). It is interesting to note that only 6-endo-dig cyclized
product 4m was obtained in 65% yields under standardized condi-
tion (Scheme 3, i). To additionally support the above controlled
experiment, we performed another set of reaction; we reacted al-
kyne 1i with amino alcohol 2a under standardized condition and
as expected only 6-endo-dig cyclized product 4n was obtained in
43% yield (Scheme 3, ii). The above two controlled experiments
support the participation of pyridyl nitrogen in the regioselective
formation of 5-exo-dig cyclized products.
A plausible mechanism for the designed approach is shown in
Scheme 4. The reaction of alkyne 1 and amino alcohol 2 generates
intermediate P via possible hydrogen bonding with pyridyl nitro-
gen and ethanol in the presence of AgOTf. The intermediates Q
can be generated by the intramolecular attack of the OH on the
imine carbon, which leads to the regioselective formation of com-
pound 3 by 5-exo-dig attack.19
we investigated the scope of the developed chemistry using a vari-
ety of o-alkynylquinoline-3-carbaldehydes 1a–h and amino alco-
hols 2a–c for the selective synthesis of 5-exo-dig cyclized
products 3a–l (Table 2). Alkynes bearing electron-rich substituents
at R2 reacted well with substrate 2a to afford the desired products
3a–d in 72–77% yields (entries 1–4). Substrates 1e and 1g, which
bear a phenyl substituent at R2, provided the products 3e and 3g
in 68% and 72% yields, respectively (entries 5 and 7). However,
when alkyne 1f bearing an electron-withdrawing-substituted
was employed, an inseparable mixture of compounds was obtained
(entry 6). The reaction of L-threonine methyl ester hydrochloride
2b with alkyne 1a and 1e afforded the products 3h and 3i in 78%
and 70% yields, respectively (entries 8 and 9). The cyclohexyl-
substituted alkyne 1h was also found to be compatible, furnishing
the desired product 3j in 65% yield (entry 10). The reaction of sub-
strates 1a and 1e with (S)-phenylglycinol (2c) provided the diaste-
reoselective products 3k and 3l in 75% and 72% yields, respectively
(entries 11 and 12).
It is evident from the results of Table 2 that substrate 1a–h un-
der Ag(I) catalysis afforded the 5-exo-dig cyclized products 3a–l
regioselectively in good yields (Table 2).18
In summary, we have described a regio- and stereoselective
synthesis of oxazolo-fused pyrroloquinolines by the reaction o-

R. R. Jha et al. / Tetrahedron Letters 55 (2014) 2603–2608
2607
H
O
N
H
Ph
CHO
O
Ph
H
H
HO
i)
AgOTf (10 mol %)
EtOH, 70 °C
+
N
H
Ph
+
H2N
Ph
Ph
Ph
H
1i
2c
4m, 65%
3m
, 0%
O
H
H
O
H
COOMe
CHO
AgOTf (10 mol %)
H
HO
ClH.H2N
N
Et N
N
ii)
(1.1 equiv)
3
COOMe
+
H
+
Ph
COOMe
EtOH, 70 °C
Ph
3n, 0%
Scheme 3. Controlled experiment confirming the participation of pyridyl nitrogen in the regioselective formation of 5-exo-dig cyclized products.
Ph
4n
, 43%
H
2a
1i
HO
H
OMe
HO
H2N
2
H
N
O
CO2Me
N
H
R1
P
O
H
OMe
Ag
CHO
O
AgOTf/EtOH
N
H2O
O
Et
N
1
N
H
g
i
R1
d
-
R1
o
x
e
-
5
Ag
Q
O
H
O
H
Et
N
COOMe
N
R1
3
H
Scheme 4. Plausible mechanism.
3. (a) Ghosh, A. K.; Mathivanan, P.; Cappiello, J. Tetrahedron: Asymmetry 1998, 9, 1;
(b) Gómez, M.; Muller, G.; Rocamora, M. Coord. Chem. Rev. 1999, 193, 769; (c)
Johnson, J. S.; Evans, D. A. Acc. Chem. Res. 2000, 33, 325; (d) Braunstein, P.;
Naud, F. Angew. Chem., Int. Ed. 2001, 40, 680; (e) Rechavi, D.; Lemaire, M. Chem.
Rev. 2002, 102, 3467; (f) McManus, H. A.; Guiry, P. J. Chem. Rev. 2004, 104, 4151.
4. Ariens, E. J. Med. Res. Rev. 1986, 6, 451.
5. (a) Jin, Z. Nat. Prod. Rep. 2003, 20, 584; (b) Lewis, J. R. Nat. Prod. Rep. 2002, 19,
223; (c) Roy, R. S.; Gehring, A. M.; Milne, J. C.; Belshaw, P. J.; Walsh, C. T. Nat.
Prod. Rep. 1999, 16, 249; (d) Wipf, P.; Venkatraman, S. Synlett 1997, 1; (e) Gant,
T. G.; Meyers, A. I. Tetrahedron 1994, 50, 2297.
alkynylaldehydes with inexpensive chiral amino esters under mild
reaction conditions. The stereochemistry and structures of the 5-
exo-dig cyclized products were supported by NOESY and X-ray
crystallography studies. The possible participation of the pyridine
ring in the regioselective formation of 5-exo-dig cyclized products
was well supported by the controlled experiments. Further inves-
tigations using this synthetic protocol are in progress and will be
reported in due course.
6. (a) Juhász, M.; Lázár, L.; Fülöp, F. Tetrahedron: Asymmetry 2011, 22, 2012; (b)
Fukuhara, T.; Hasegawa, C.; Hara, S. Synthesis 2007, 10, 1528; (c) Graham, T. H.
Org. Lett. 2010, 12, 3614.
Acknowledgments
7. (a) Gaumont, A.-C.; Gulea, M.; Levillain, J. Chem. Rev. 2009, 109, 1371; (b)
Calmes, M.; Escale, F.; Paolini, F. Tetrahedron: Asymmetry 1997, 8, 3691.
8. (a) Seechurn, C. C. C. J.; Kitching, M. O.; Colacot, T. J.; Snieckus, V. Angew. Chem.,
Int. Ed. 2012, 51, 5062; (b) Magano, J.; Dunetz, J. R. Chem. Rev. 2011, 111, 2177;
(c) Gladysz, J. A. Chem. Rev. 2011, 111, 1167; (d) Cahiez, G.; Moyeux, A. Chem.
Rev. 2010, 110, 1435; (e) Jiang, B.; Rajale, T.; Wever, W.; Tu, S.-J.; Li, G. Chem.
Asian J. 2010, 5, 2318; (f) Akritopoulou-Zanze, I.; Djuric, S. W. Top. Heterocycl.
Chem. 2010, 25, 231; (g) Wessjohann, L. A.; Rivera, D. G.; Vercillo, O. E. Chem.
Rev. 2009, 109, 796; (h) Ackermann, L.; Vicente, R.; Kapdi, A. R. Angew. Chem.,
Int. Ed. 2009, 48, 9792; (i) Chen, X.; Engle, K. M.; Wang, D.; Yu, J. Q. Angew.
Chem., Int. Ed. 2009, 48, 5094; (j) Arndtsen, B. A. Chem. Eur. J. 2009, 15, 302; (k)
Roglans, A.; Quintana, A. P.; Moreno-Manas, M. Chem. Rev. 2006, 106, 4622; (l)
Nakamura, I.; Yamamoto, Y. Chem. Rev. 2004, 104, 2127; (m) Hassan, J.;
Sevignon, M.; Gozzi, C.; Schulz, E.; Lemaire, M. Chem. Rev. 2002, 102,
1359.
9. (a) Yu, X.; Wu, J. J. Comb. Chem. 2010, 12, 238; (b) Patil, N. T.; Mutyala, A. K.;
Lakshmi, P. G. V. V.; Raju, P. V. K.; Sridhar, B. Eur. J. Org. Chem. 2010, 1999; (c)
Yanada, R.; Obika, S.; Kono, H.; Takemoto, Y. Angew. Chem., Int. Ed. 2006, 45,
3822.
10. (a) Pellissier, H. Chem. Rev. 2013, 113, 442; (b) Friedman, A. A.; Panteleev, J.;
Tsoung, J.; Huynh, V.; Lautens, M. Angew. Chem., Int. Ed. 2013, 52, 9755; (c)
Tietze, L. F.; Hungerland, T.; Eichhorst, C.; Dufert, A.; Maab, C.; Stalke, D. Angew.
Chem., Int. Ed. 2013, 52, 3668; (d) Grossmann, A.; Enders, D. Angew. Chem., Int.
Ed. 2012, 51, 314; (e) Liu, H.; El-Salfiti, M.; Lautens, M. Angew. Chem., Int. Ed.
2012, 51, 9846; (f) Tietze, L. F.; Brasche, G.; Gericke, K. M. Angew. Chem., Int. Ed.
2007, 46, 2977; (g) Tietze, L. F. Chem. Rev. 1996, 96, 115.
We thank DST and DU-DST PURSE Grant for the financial sup-
port and USIC University of Delhi for Instrumentation facility. R.
R. J. and T. A. are thankful to CSIR for the fellowships.
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2014.
02.103.
References and notes
1. (a) Antoniotti, S.; Dunach, E. Tetrahedron Lett. 2002, 43, 3971; (b) Dua, R.;
Shrivastava, S.; Sonwane, S. K.; Srivastava, S. K. Adv. Biol. Res. 2011, 5, 120; (c)
Gil, C.; Bräse, S. J. Comb. Chem. 2009, 11, 175; (d) Bhadra, K.; Kumar, S. Med. Res.
Rev. 2011, 31, 821; (e) Fan, H.; Peng, J.; Hamann, M. T.; Hu, J.-F. Chem. Rev. 2008,
108, 264; (f) Vincent, G.; Williams, R. M. Angew. Chem., Int. Ed. 2007, 46, 1517;
(g) Bentley, K. W. Nat. Prod. Rep. 2006, 23, 444; (h) McGrane, P. L.; Livinghouse,
T. J. Am. Chem. Soc. 1993, 115, 11485; (i) Kwan, J. C.; Ratnayake, R.; Abboud, K.
A.; Paul, V. J.; Luesch, H. J. Org. Chem. 2010, 75, 8012; (j) Agarwal, S.; Cämmerer,
S.; Filali, S.; Fröhner, W.; Knöll, J.; Krahl, M. P.; Reddy, K. R.; Knolker, H.-N. Curr.
Org. Chem. 2005, 9, 1601.
11. (a) Hu, Y.; Yi, R.; Wu, F.; Wan, B. J. Org. Chem. 2013, 78, 7714; (b) Ishida, T.;
Kikuchi, S.; Yamada, T. Org. Lett. 2013, 15, 3710; (c) Ishida, T.; Kikuchi, S.;
Yamada, T. Org. Lett. 2013, 15, 848; (d) Yamamoto, Y. Chem. Rev. 2008, 108,
3199.
2. (a) Saravanan, P.; Corey, E. J. J. Org. Chem. 2003, 68, 2760; (b) Cardillo, G.;
Gentilucci, L.; Tolomelli, A. Aldrichim. Acta 2003, 36, 39; (c) Meyers, A. I. J. Org.
Chem. 2005, 70, 6137; (d) Gnas, Y.; Glorius, F. Synthesis 2006, 1899.

2608
R. R. Jha et al. / Tetrahedron Letters 55 (2014) 2603–2608
12. (a) Jha, R. R.; Saunthwal, R. K.; Verma, A. K. Org. Bio. Chem. 2014, 12, 552; (b)
Jha, R. R.; Danodia, A. K.; Kumar, S.; Verma, A. K. Tetrahedron Lett. 2014, 55, 610;
(c) Verma, A. K.; Choudhary, D.; Saunthwal, R. K.; Rustagi, V.; Patel, M.; Tiwari,
R. K. J. Org. Chem. 2013, 78, 6657; (d) Verma, A. K.; Kotla, S. K. R.; Choudhary, D.;
Patel, M.; Tiwari, R. K. J. Org. Chem. 2013, 78, 4386; (e) Shukla, S. P.; Tiwari, R.;
Verma, A. K. Tetrahedron 2012, 68, 9035; (f) Aggarwal, T.; Jha, R. R.; Tiwari, R.
K.; Kumar, S.; Kotla, S. K. R.; Kumar, S.; Verma, A. K. Org. Lett. 2012, 14, 5184; (g)
Verma, A. K.; Rustagi, V.; Aggarwal, T.; Singh, A. P. J. Org. Chem. 2010, 75, 7691;
(h) Rustagi, V.; Tiwari, R. K.; Verma, A. K. Eur. J. Org. Chem. 2012, 4590; (i)
Rustagi, V.; Aggarwal, T.; Verma, A. K. Green Chem. 2011, 13, 1640; (j) Aggarwal,
T.; Kumar, S.; Dhaked, D. K.; Tiwari, R. K.; Bharatam, P. V.; Verma, A. K. J. Org.
Chem. 2012, 77, 8562; (k) Aggarwal, T.; Imam, M.; Kaushik, N. K.; Chauhan, V.
S.; Verma, A. K. ACS Comb. Sci. 2011, 13, 530; (l) Verma, A. K.; Aggarwal, T.;
Rustagi, V.; Larock, R. C. Chem. Commun. 2010, 4064.
13. (a) Ouyang, H.-C.; Tang, R.-Y.; Zhong, P.; Zhang, X.-G.; Li, J.-H. J. Org. Chem.
2011, 76, 223; (b) Ohta, Y.; Kubota, Y.; Watabe, T.; Chiba, S.; Oishi, H.; Fujii, S.;
Ohno, H. J. Org. Chem. 2009, 74, 6299; (c) Yu, M.; Wang, Y.; Li, C.-J.; Yao, X.
Tetrahedron Lett. 2009, 50, 6791; (d) Ye, Y.; Ding, Q.; Wu, J. Tetrahedron 2008,
64, 1378; (e) Gao, K.; Wu, J. J. Org. Chem. 2007, 72, 8611; (f) Ding, Q.; Wu, J. Org.
Lett. 2007, 9, 4959; (g) Asao, N.; Iso, K.; Salprima, Y. S. Org. Lett. 2006, 8, 4149;
(h) Asao, N.; Salprima, Y. S.; Nogami, T.; Yamamoto, Y. Angew. Chem., Int. Ed.
2005, 44, 5526; (i) Yue, D.; Della Ca, N.; Larock, R. C. Org. Lett. 2004, 6, 1581; (j)
Yao, T.; Campo, M. A.; Larock, R. C. Org. Lett. 2004, 6, 2677.
16. Crystallographic data of compounds 3h and 3l have been deposited at the
Cambridge Crystallographic data centre with file number 931654, 946913
respectively, and Copies of these data can be obtained free of charge on
application to CCDC, email: deposit@ccdc.cam.ac.
17. See Supporting information.
18. General procedure for the synthesis of Oxazolo fused pyrrolo[3,4-b]quinolines (3a).
An oven-dried Schlenk tube with a Teflon screw valve was charged with
1.1 equiv of
L
(ꢀ)Serine methyl ester hydrochloride 2a, EtOH (2.0 mL), 1.1 equiv
Et3N, 0.5 mmol of the 2-alkanylaldehyde 1a, and AgOTf (10 mol %). The Schlenk
tube was capped with a rubber septum and then evacuated and backfilled with
nitrogen. The septum was then replaced with a Teflon screw valve, and the
Schlenk tube was sealed. The reaction mixture was heated to 70 °C until 2-
alkanylaldehyde 1a had been completely consumed (as determined by TLC)
and was allowed to cool to room temperature. The reaction mixture was
diluted with ethyl acetate (10 mL) and water (15 mL). Organic layer was
concentrated under reduced pressure. The crude material so obtained was
purified by column chromatography on silica gel. (3S,11bS,Z)-Methyl–5-(4-
methylbenzylidene)–2,3,5,11b
tetrahydrooxazolo
[3’,2’:1,5]pyrrolo[3,4-
b]quinoline–3-carboxylate(3a). The product was obtained as a yellow needles
(DCM/Ether), mp: 161–163 °C;
½
a 3D2
ꢁ
= ꢀ143.4 (c 0.1, MeOH): 1H NMR
(400 MHz, CDCl3) d: 8.22 (s, 1H), 8.07 (d, J = 8.8 Hz, 1H), 7.80 (d, J = 8.1 Hz,
1H), 7.68 (t, J = 8.1 Hz, 1H), 7.49–7.45 (m, 3H), 7.08 (d, J = 8.0 Hz, 2H), 6.96 (s,
1H), 6.35 (s, 1H), 4.25–4.22 (m, 1H), 4.00–3.97 (m, 1H), 3.76 (s, 3H), 3.67–
3.63(m, 1H), 2.49 (s, 3H); 13C NMR (100 MHz, CDCl3) d: 171.9, 156.5, 149.9,
143.4, 136.7, 132.4, 132.1, 130.4, 129.4, 129.3, 129.1, 128.9, 128.5, 128.0, 126.5,
105.5, 95.3, 69.0, 64.6, 52.5, 21.3. HRMS (ESI) (M)+ calcd for C23H20N2O3:
372.1474, found 372.1474.
14. (a) Katritzky, A. R.; He, H.-Y.; Verma, A. K. Tetrahedron: Asymmetry 2002, 13,
933; (b) Katritzky, A. R.; Xu, Y.-J.; He, H.-Y.; Steel, P. J. J. Chem. Soc., Perkin Trans.
1 2001, 1767.
15. The stereochemistry of the products 3a_l was assigned based on the NOESY and
X-ray structure of 3h, 3l and the similarity in the 1H NMR spectral pattern of
3a_l.
19. Godet, T.; Vaxelaire, C.; Michel, C.; Milet, A.; Belmont, P. Chem. Eur. J. 2007, 13,
5632.