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S. Naskar et al. / Tetrahedron Letters 52 (2011) 1527–1531
Table 3 (continued)
Entrya Isoquinoline Phenacyl bromide/bromoacetic
acid ester
Chromone-3-carboxal-
dehyde
Pyrrolo[2,1-a] isoquinoline
Yieldb
(%)
R3 = Ph)
14
15
1a
1a
2e
2e
3b
3c
4n (R1 = R2 = H, R4 = Me,
94
90
R
3 = Ph)
4o (R1 = R2 = H, R4 = Cl,
R3 = Ph)
16
17
18
1a
1a
2f (R2 = R3 = Cl)
2f
2a
3a
3c
3a
4p (R1 = R4 = H, R2 = R3 = Cl)
4q (R1 = H, R2 = R3 = R4 = Cl)
4r (R1 = NO2,
90
90
92
1b
(R1 = NO2)
R2 = R3 = R4 = H)
19
20
1b
2a
3b
3a
4s (R1 = NO2, R2 = R3 = H,
94
90
R
4 = Me)
1b
2g (R2 = H, R3 = Cl)
4t (R1 = NO2, R2 = R4 = H,
R3 = Cl)
R1
O
O
R2
Br
O
R1O
N
OH
O
21
22
23
24
1a
1a
1a
1a
2h (R1 = Me)
2i (R1 = Et)
2i
3a
3a
3c
3a
4u (R1 = Me, R2 = H)
4v (R1 = Et, R2 = H)
4w (R1 = Et, R2 = Cl)
4x (R1 = tBu, R2 = H)
92
92
90
90
2j (R1 = tBu)
a
Reaction conditions: isoquinoline (1 mmol), phenacyl bromide/bromoacetic acid ester (1 mmol), chromone-3-carboxaldehyde
(1 mmol), water (50 ml), DBU (1 mmol), CTAB (4 mmol), 1 h in air.
b
Yield of isolated pure products.
olinium ylide (B) by reacting with a base. A regioselective 1,3-dipo-
lar cycloaddition reaction occurs between the electron deficient
336033; or deposit@ccdc.cam.ac.uk)) associated with this article
C2–C3
p bond of chromone-3-carboxaldehyde (3a) and the isoquin-
oline ylide (B), forming an unstable intermediate C, which after
deformylation11a and ring opening14 leads to dihydro-pyrrol-
o[2,1-a]isoquinoline derivative D, which readily aromatizes to give
4a.
In order to establish the generality and scope of this new meth-
odology, we used different derivatives of isoquinoline, phenacyl
bromide/bromoacetic acid ester and chromone-3-carboxaldehyde.
The results are summarized in Table 3.
In summary, we have developed an environmentally benign
protocol for the synthesis of pyrrolo[2,1-a]isoquinolines15,16 with
excellent yields and in a short reaction time using easily available
starting materials in aqueous micellar medium. The study demon-
strates the feasibility of preparation of libraries of biologically ac-
tive pyrrolo[2,1-a]isoquinoline analogues for lead discovery and/
or optimization in medicinal chemistry.
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Acknowledgements
The authors express their gratitude to the Director, IICB for lab-
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(CSIR) for providing the funding and fellowships to S.N., A.H.,
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and Mr. K. Sarkar for recording the spectra and Dr. B. Achari, Emer-
itus Scientist, CSIR, for his valuable suggestions.
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Supplementary data
Supplementary data (1H and 13C NMR spectra of all new com-
pounds. Crystallographic data in CIF format are available free of
charge via the Internet at CCDC 796010 & 796011. These data
tre, 12, Union Road, Cambridge CB2 1EZ, UK; fax: +44 1223