A new (3+3) annulation route to isoquinoline-3-carboxylates

Article abstract of DOI:10.1016/S0040-4039(02)01000-6

A new synthesis of isoquinoline-3-carboxylates based on the palladium(0)-catalysed Heck-type arylation of 2-amidoacrylates with the appropriate 2-substituted iodobenzene is reported.

Full text of DOI:10.1016/S0040-4039(02)01000-6

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 5079–5081
†
A new (3+3) annulation route to isoquinoline-3-carboxylates
Shital K. Chattopadhyay,* Susama Maity, Benoy K. Pal and Srikanta Panja
Department of Chemistry, University of Kalyani, Kalyani 741235, West Bengal, India
Received 15 April 2002; revised 15 May 2002; accepted 24 May 2002
Abstract—A new synthesis of isoquinoline-3-carboxylates based on the palladium(0)-catalysed Heck-type arylation of 2-ami-
doacrylates with the appropriate 2-substituted iodobenzene is reported. © 2002 Elsevier Science Ltd. All rights reserved.
The isoquinoline ring system is found in many
alkaloids and for this and other reasons the synthesis
demonstrated that Pd(0)-catalysed olefination of
haloaromatics with 2-amidoacrylates gives the corre-
sponding 2-amidocinnamates with very high stereose-
lectivity. In this communication, we wish to disclose
how this selectivity can be exploited for a cyclo-func-
tionalisation leading to a new synthesis of isoquinoline-
3-carboxylates.
1
of isoquinoline derivatives has received considerable
2
attention. Most of the classical methods employ com-
paratively harsh conditions, and therefore have obvious
limitations. A few milder approaches have also been
3
reported. In recent years, a number of heterocyclic ring
4
systems have been conveniently prepared using palla-
8
dium(0)-catalysed reactions, and annulation strategies
based on such catalysis have recently been reported for
We argued that a Heck-type olefination of a 2-substi-
tuted iodoarene of type 1 (Fig. 1) with the 2-amido-
acrylate 2 should give a substrate 3 containing an
5
6
7
the synthesis of isoquinolines. We, and others, have
Figure 1.
Keywords: Heck reaction; 2-amidoacrylates; isoquinoline-3-carboxylates.
*
Corresponding author. Fax: (+) 91 (033) 582 8282; e-mail: skc@klyuniv.ernet.in
This paper is dedicated to Professor T. Frejd, University of Lund, Sweden.
†
0
040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)01000-6

5
080
S. K. Chattopadhyay et al. / Tetrahedron Letters 43 (2002) 5079–5081
electrophilic and a nucleophilic partner for a CꢀN bond
with each of the olefins 2a and 2b, the intermediate
cinnamates 3d–e were obtained in 87 and 91% yields,
respectively. Simple treatment of these products 3d–e
with pyridinium p-toluenesulfonate (PPTS) or p-toluene-
sulphonic acid resulted in the formation of the desired
isoquinoline-3-carboxylates (5a–b) in greater than 95%
6,7
forming ring closing reaction. The known Z-selectivity
of the reaction delivers these complementary functional-
ities in the proximity necessary for a facile cyclisation.
This proved to be a realistic proposition when methyl
2
-iodobenzoate was reacted with methyl 2-acetami-
11
yield (Scheme 2).
doacrylate 2a using a catalytic amount of palladium
acetate under Jeffery’s conditions for Heck-type cou-
9
Isoquinoline-3-carboxylates and 1,2-dihydroisoquino-
line-3-carboxylates are important compounds in view of
pling. Methyl isoquinolin-1-one-3-carboxylate 4 was the
only product isolated (61%). The cinnamate 3a, possibly
formed as an intermediate (not isolated) must have
undergone in situ cyclisation with the loss of the N-acetyl
group (Scheme 1).
1
2
their use in the synthesis of designed peptidomimetics.
13
Several syntheses including two recent ones have been
reported for the synthesis of isoquinoline-3-carboxylates.
The simplicity of our method may complement those
14
existing in the literature.
Oxoquinoline-3-carboxylic acids (ciprofloxacin, nali-
daxic acid, norfloxacin and others) are well known
10
antibacterial agents and therefore synthesis of the
corresponding isoquinoline analogues is of significance.
On the other hand, the analogous reaction of 2-iodobenz-
aldehyde with the same olefin 2a under identical condi-
tions did not provide the expected methyl isoquinoline-3-
carboxylate; instead the product was characterised as the
Acknowledgements
Financial assistance from the CSIR, New Delhi (Grant
No. 01/1676/00/EMR-II) is gratefully acknowledged.
2
-substituted benzyl alcohol 3b (62%). Olefin 2b similarly
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