UNIVERSIDAD AUTÒNOMA DEL ESTADO DE MÉXICO

Facultad de Química

Research Protocol

ENANTIOSELECTIVE SYNTHESIS OF HETEROCYCLIC DERIVATIVES OF

PYRROLO [1,2-a] ISOQUINOLINES THROUGH INTERMEDIARIES TRAINING
ISOINDOLONES
Academic advisor: David Corona Becerril
Student: Juan Javier Mejía Vega

SUMMARY

The need to resolve racemic mixtures when an asymmetric center is produced

has been a serious limitation in synthetic chemistry. In industry, where usually
required a single isomer, the problem is particularly severe with purification
methods racemic mixtures, as they are highly expensive processes. Use of
enantioselectivity in asymmetric catalytic reactions became an area of interest for
its applications in synthesis of enantiomeric pure compounds currently is a highly
profitable industrial scale method. As part of this study, a new synthetic route
which includes the formation of an intermediary isoindolone will be developed
and from which carrying out enantioselective reactions is obtained pyrrolo [1,2-a]
isoquinolines analogous to corresponding structures biologically active alkaloids
found in nature.

JUSTIFICATION

The idea of developing a synthesis method that allows access to enantiomerically

pure compounds as obtaining pyrrolo [2,1-a] isoquinolines through isoindolone
intermediaries has as its foundation the more effectively conceive and economic
products of pharmaceutical interest. In this context, the proposed methodology
for the realization of this project, it also seeks an important role in the generation
of new knowledge and experience for the benefit of society contribution. The
advantages associated with the use of this synthetic route is the availability of
materials and high selectivity in obtaining the desired products and thus the
generation of byproducts is minimal, making this methodology is highly desirable
academic and industrially. It is believed that enantiomeric pure compounds
obtained during this project will have some biological activity and although this
study will not be addressed here, the availability of these new structures for
knowledge of their reactivity can be a long-term goal opening the way to further
studies.

HYPOTHESIS

It is possible to carry out the formation of heterocyclic derivatives of pyrrolo [1,2-

a] isoquinolines through a synthesis strategy as important step involving
stereoselective reduction of isoindolones intermediaries.

OBJECTIVES

General objective

Elaborate derivatives of heterocyclic compounds pyrrolo [1,2-a] isoquinolines

stereoselectively through intermediaries isoindolones.

Specific objectives

 Carry out the formation of vinyl azides through an aldol condensation

reaction between aldehydes corresponding derivatives and their reaction
with ethyl azidoacetate.
 Get vinyl iminophosphorane derivatives using as starting material the vinyl
azides from the last step and its reaction with triphenylphosphine using
Staudinger strategy.
 Get isoindolone intermediaries from the reaction of ortho-vinyl
iminophosphoranes with aromatic dialdehydes.
 Reduce enantioselectively the portion of alkene present in isoindolone
intermediaries through employment of a chiral catalyst derived from
rhodium.
  Synthesis of pyrrolo [1,2-a] isoquinoline derivatives through a cyclization
process of enantiomerically pure compounds of isoindolones
intermediaries by a α-amidoalquilación reaction.
 Characterize each of the intermediates and the final products of the
synthesis route by spectroscopic and spectrometric media.

METHODOLOGY

Synthetic route for the formation of pyrrolo [1,2-a] isoquinoline derivatives.

(1) R1= (3,4 –OCH3), (2) R1=H, (3) R1=(4 –NMe2), (4) R1=(4 –CO2Et), (5)
R1=(4 –NO2)

=
 SCHEDULE
Period Year 2016 2017 2018
Activity Month 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
Literature review
Synthesis and
characterization of
isoindolone
intermediaries
Isoindolone
enantioselective
reduction derivatives
and their
characterization
Synthesis and
characterization of
pyrrolo [1,2-a]
isoquinoline
Method A
Synthesis and
characterization of
pyrrolo [1,2-a]
isoquinoline
Method B
Article
Thesis
Obtaining Degree
 BIBLIOGRAPHY
13
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NMR and reaction mechanism studies of novel isoindolones derivatives, obtained
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of a Pyridine Ring into a Preformed Pyridine One: Synthesis of
Naphthyridine, Pyrido[1,2-c] pyrimidine and Pyrido[1,2-clquinazoline
Derivatives. Tetrahedron Letters 48 (22), pp: 4601-4616.
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Org. Chem., 73, pp: 3928-3930.
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Synthesis of Pyrrolo[2,1-a]isoquinolines. J. Org. Chem., 70, pp: 10368-10374.
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Reagents. Ready Access to Isoquinoline Derivatives via N-Acyliminium Ions and
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