Issue in Honor of Prof. Joan Bosch ARKIVOC 2007 (iv) 84-91
Synthesis of new indolo[1,2-b]isoquinoline derivatives from N-(2-
bromobenzyl)indole
Roberto Sanz,*
,a
José M. Ignacio,
a
M. Pilar Castroviejo,
a
and Francisco J. Fañanás
b
a
Área de Química Orgánica, Departamento de Química, Facultad de Ciencias, Universidad de
Burgos, Pza. Misael Bañuelos s/n, E-09001, Burgos, Spain
b
Instituto de Química Organometálica “Enrique Moles” (Unidad Asociada al CSIC),
Universidad de Oviedo, C/ Julián Clavería 8, E-33006, Oviedo, Spain
E-mail: rsd@ubu.es
Dedicated to Prof. Dr. Joan Bosch on the occasion of his 60
th
birthday
Abstract
Optimal conditions have been established for the generation of N-(2-lithiobenzyl)-2-lithio-1H-
indole from easily available N-(2-bromobenzyl)-1H-indole. An efficient method was developed
for the synthesis of 6,11-dihydroindolo[1,2-b]isoquinoline derivatives by reaction of this indole
dianion with carboxylic esters. New and interesting fused indole derivatives have also been
synthesized.
Keywords: Indoles, organolithiums, dianions, isoquinolines, carboxylic esters
Introduction
Due to the potent biological activity exhibited by various indole derivatives, there is a continuous
demand for novel synthetic methods in this area, as well as for the preparation of new indole
derivatives.
1
Also, isoquinolines as well as their derivatives have received considerable attention
due to their interesting biological properties.
2
Indolo[1,2-b]isoquinoline derivatives are of
considerable pharmacological relevance because they represent C-analogues of tryptanthrin.
3
This kind of fused heterocyclic systems have been prepared mainly by radical cyclization,
4
palladium-catalyzed couplings,
5
and more recently, by a domino “cyclization-lactamization”
reaction of functionalized nitriles.
6
In the last years we have developed a new carbolithiation reaction of lithiated double bonds
which has allowed us the easy preparation of functionalized indole and pyrrole derivatives.
7
For
instance, N-(2-lithioallyl)-2-lithioanilines gave rise to 3-lithiomethylindoles that were trapped
with electrophiles (Scheme 1). Moreover, we and others have recently reported that carboxylic
ISSN 1424-6376 Page 84
©
ARKAT USA, Inc.