synthesis, characterization and biological screening of...
TRANSCRIPT
Synthesis, Characterization and Biological Screening of Some Heterocyclic Compounds
PRATAPSINHA B. GOREPATIL 1
INTRODUCTION
Therapeutic/ Biological Importance of Heterocycles:
Heterocyclic compounds hold a special place among the pharmaceutically
significant natural products and synthetic compounds. Syntheses of various heterocycles
have been research objective for over a century. The chemistry of heterocyclic
compounds and their synthetic routes form the platform of medicinal, chemical and
pharmaceutical research. The remarkable ability of heterocyclic nuclei to serve both as
biomimetic and reactive pharmacophores made them key elements of numerous drugs.
Heterocyclic compounds are an integral part of organic synthesis. Nearly more than
half of the known organic compounds contain at least one heterocyclic ring. Many
heterocyclic compounds occur naturally and are actively involved in biological processes,
like nucleic acid bases, which are derivatives of the pyrimidine and purine rings systems,
as being crucial to the mechanism of replication. Many dyestuffs and pigments such as
indigo (1.1), strychnine (1.2), hemoglobin (1.3) and chlorophyll (1.4) are also having
heterocyclic moiety.1 Vitamins, penicillin and some amino acids like histidine,
tryptophan, proline are also having heterocyclic compounds.
Synthesis, Characterization and Biological Screening of Some Heterocyclic Compounds
PRATAPSINHA B. GOREPATIL 2
Among the various heterocycles oxygen, nitrogen and sulfur bearing heterocycles
are immense importance to researchers as they include highly stable aromatic compounds
exhibiting wide range of biological activities such as medicine,2 agriculture,
3 veterinary
products and also as sensitizers, developers, antioxidants, copolymers, etc. During the
past decades, compounds bearing heterocyclic nuclei have received much attention due to
their chemotherapeutic value in the development of novel antimicrobials.4-5
Most of the
heterocyclic compounds with oxygen, nitrogen and sulfur as heteroatoms from the classes
like benzimidazole, benzothiazole, benzoxazole, quinoline have displayed wide range of
bioactivities. These heterocycles have been studied extensively because of their ready
accessibility; diverse chemical reactivity’s and wide range of biological activities.
Synthesis, Characterization and Biological Screening of Some Heterocyclic Compounds
PRATAPSINHA B. GOREPATIL 3
In heterocyclic compounds fused heterocycles attract attention of researchers
because of its importance as building units in pharmaceuticals. Examples include
allopurinol (1.5) as a gout therapeutic,6 sildenafil (1.6) as Viagra, tubers din (1.7) as an
anticancer agent, abacavir (1.8) as an anti HIV agent, acyclovir (1.9) as an antiviral agent
for the treatment of Herpes.
Benzofused heteroaromatic compounds, in particular benzofused azoles, are
important building blocks in biologically and therapeutically active compounds, natural
products, and functional materials.7 In benzofused azoles- Benzo-1, 3-diazoles like
benzimidazole, benzoxazole and benzothiazole have attracted much interest in diverse
areas of chemistry.8
These heterocycles have shown different pharmacological activities.
The studies of structure–activity relationship interestingly reveal that change of the
structure of substituent groups commonly results the change of its bioactivity9-13
such as
antibacterial, antiulcer (1.10), antihypertensive, antivirals, antifungals, anticancer (1.11),
Synthesis, Characterization and Biological Screening of Some Heterocyclic Compounds
PRATAPSINHA B. GOREPATIL 4
and antihistamines (1.12).14–19
These compounds are also used as ligands for asymmetric
transformations,20
exhibit nonlinear optical21
and luminescent22
/fluorescent.23
There are large numbers of synthetic benzo-1, 3-diazole compounds with
additional important applications and many are valuable intermediates in synthesis which
increases the great interest in both fields, theoretical and classical organic synthesis.
Recent Synthetic Protocols:
Following is a brief review on alternative safer and coast effective synthetic protocols.
“Classical organic synthesis seems to be inefficient and is now under pressure because
of increasing environmental awareness. How can it be improved?”
Organic chemistry is a vibrant and growing scientific discipline that touches a
vast number of scientific areas. It’s started as the chemistry of life, when that was thought
to be different from the chemistry in the laboratory. A reasonable way to define organic
chemistry is the study of the relationship between the structure and properties of carbon
compounds. The function of organic synthesis is to provide this study with access to
these compounds in a pure form, either by extraction from natural resources or via
synthesis, hence, “Synthesis is the heart of Chemistry”.
Organic synthesis is one of the foundation stone of the natural sciences. Synthetic
organic chemistry provides efficient routes and novel methods to synthesize molecules.
The development of excellent synthetic reactions leads to the creation of new organic
Synthesis, Characterization and Biological Screening of Some Heterocyclic Compounds
PRATAPSINHA B. GOREPATIL 5
compounds, often opening up completely new areas of chemistry. Organic synthesis has
provided valuable materials in the form of medicines, food products, cosmetics, dyes,
paints, agrochemicals, biomolecules and high-tech substances like polymers. Chemists
have used their knowledge and skill to prepare a large number of new materials, which
are far better and more useful than the natural products such as high-tech polymers,
designer drugs, genetic materials and new energy sources.
Finally, organic synthesis is also undertaken with the goal of developing the most
economic route for the industrial synthesis of a product for which there is a definite need.
Nowadays, the green chemistry revolution is providing an enormous number of
challenges to those who practice chemistry in industry, education and research. With
these challenges however, there are an equal number of opportunities to discover and
apply new chemistry and to enhance the much-tarnished image of chemistry.24
In this
context would like to introduce the new image of chemistry, the challenge for today’s
organic chemists is not only synthesis of organic molecules but also to develop an
innovative, cleaner and greener process.
Green chemistry, also called sustainable chemistry, is a philosophy of chemical
research and engineering that encourages the design of products and processes that
minimize the use and generation of hazardous substances. Whereas environmental
chemistry is the chemistry of the natural environment, and of pollutant chemicals in
nature, green chemistry seeks to reduce and prevent pollution at its source. The focus is
on minimizing the hazard and maximizing the efficiency of any chemical choice. It is
distinct from environmental chemistry which focuses on chemical phenomena in the
environment. Examples of applied green chemistry are supercritical water oxidation, on
water reactions, and solvent free reactions. In 2005 Ryoji Noyori identified three key
developments in green chemistry: use of supercritical carbon dioxide as green solvent,
aqueous hydrogen peroxide for clean oxidations and the use of hydrogen in asymmetric
synthesis.25
The challenge for chemists and others is to develop new processes that allow to
achieve environmental benefits that are now required, in terms of safe chemistry. This
Synthesis, Characterization and Biological Screening of Some Heterocyclic Compounds
PRATAPSINHA B. GOREPATIL 6
requires a new approach which sets out to reduce the materials and energy intensity of
chemical processes and products, minimize or eliminate the dispersion of harmful
chemical in the environment, maximize the use of renewable resources and extend the
durability and recyclability of the products. Some of the challenges for chemists include
the discovery and development of new synthetic pathways using alternative feed stocks
or more selective chemistry, identifying alternative reaction conditions and the
preservation of resources and the avoidance of toxic reagents as well as toxic solvents26
for improved selectivity and energy minimization and designing less toxic and inherently
safer chemicals. In chemical synthesis, the ideal will be a combination of a number of
environmental, health and safety, and economic targets (Fig. 1.1).
That’s why organic chemists are focusing on one-pot procedures. Indeed,
effective organic synthesis is predicated on site-isolation, the physical separation of
reagents or catalysts from each other. Synthetic organic chemists typically achieve site-
isolation by using separate flasks or reactors. The main problem, related to this kind of
“multi-pots” processes is amenable to the waste of solvents, because each step requires an
extraction, so, formation of an aqueous layer that must be treated at all. Beyond solvent,
high yielding reactions often produce salts and other impurities that must be removed to
avoid deleterious effects on the downstream transformations. Serial reactions and
purifications require massive amounts of solvents and materials.
Figure 1.1
ATOM EFFICIENT
SIMPLE METHOD
MAXIMUM YIELD
AVAILABLE MATERIALS
ENVIRONMENTALLY
ACCEPTABLE
NO WASTE REAGENTS
ONE STEP
SAFE
IDEAL
SYNTHESIS
Synthesis, Characterization and Biological Screening of Some Heterocyclic Compounds
PRATAPSINHA B. GOREPATIL 7
Improving efficiency is one of the main pursuits of modern organic synthesis
research.27-28
This is further reinforced by the increasing concerns of environmental
protection and sustainability in past decades. To date the design, development, and
utilization of efficient environmentally benign synthetic process has become a
conscientious choice of synthetic chemists.29-30
One attractive strategy is to design and
develop a novel one-pot multistep synthesis that helps simplify reaction handling and
product purification, improve synthetic efficiency, and reduce solvent consumption and
disposal. This will ultimately help reduce consumption of natural resources, minimize the
potential, harmful impact of various chemicals on environment, and increase
sustainability.31
In contrast, modern synthesis management must seek procedures that
allow the formation of several bonds, whether C−C, C−O or C−N in one process. This
new approach is called “One-Pot” philosophy; it can be defined as, a strategy to improve
the efficiency of a chemical reaction whereby a reactant is subjected to successive
chemical transformation in just one reactor.
Multicomponent reactions (MCRs) have already created a stir among the organic
community and emerged as a powerful tool for the construction of novel and complex
molecular structures due to their advantages over conventional multistep synthesis;32
the
major advantages of MCRs include lower costs, shorter reaction times, high atom
economy, energy saving, and avoidance of time consuming expensive purification
processes.33
It is the fact that MCRs are generally much more environment friendly, and
offer instantaneous access to large compound libraries with diverse functionalities, with
the avoidance of protection and deprotection steps, for possible combinatorial surveying
of structural variations.34
Considering the need of incorporation of the green tools and to develop
convenient an efficient synthetic protocols for organic transformation that time catalyst
play an important role. Catalysis is broadly divided into homogenous and heterogeneous
catalysis. Homogenous catalytic reaction is one in which the reactant and catalyst are in
the same phase and if the reactants and catalyst are in different phase, it is heterogeneous
catalysis. However, many of these homogeneous catalytic processes suffered from a
Synthesis, Characterization and Biological Screening of Some Heterocyclic Compounds
PRATAPSINHA B. GOREPATIL 8
serious limitation, namely, the separation and recovery of the catalyst. Recently the use of
heterogeneous catalysts35-47
has received considerable importance in organic synthesis
because of ease of handling, enhanced reaction rates, greater selectivity, and simple
workup. Furthermore, the exploitation of heterogeneous catalysts permits the easy
separation and reuse of the catalysts. This methodology constitutes a powerful tool in
chemistry, allowing extremely complex chemical transformations to take place in a one
pot, cleaner, and more efficient process. Transition metal catalysis is one of the
research areas with the richest history and chemistry. A wide range of transition metal-
catalyzed reactions, including hydrogenation, cross-couplings, metathesis, and various
addition and oxidation reactions, are utilized on industrial scales to manufacture valuable
products such as polymers, pesticides and human pharmaceuticals.48-55
The importance of catalysis to the pharmaceutical industry has steadily increased
over the past two decades. This was due to several interrelated factors: the increasing
regulatory requirements, for example, policies on single enantiomer drugs56
and
environmental protection, the pressure to reduce drug development cost and time; the lost
revenue for even a modestly successful drug can easily reach millions of dollars per day,
and the continued discovery of new practical catalysts from both academia and industry.
The interplay of all these factors resulted in the current rapid uptake of catalysis in
pharmaceutical research, development and production.57
In view of the above biological and pharmaceutical significance of the
heterocyclic compounds chemists developed newer convenient and rapid synthetic routes
for these value added heterocycles. It is reviewed that the classical cyclocondensation
reported for obtaining therapeutically active heterocycles bearing S/O and N heteroatoms
are time consuming, low yielding, requiring toxic solvents and catalysts and to
accomplish these cyclocondensations the catalysts employed are non-recyclable and work
up procedures of the isolations of the products are found to be more tedious.
Since last two decades efforts are also found to be directed to employ some of the
green tools to accelerate and to make synthetic routes environmentally benign for getting
bioactive heterocycles.
Synthesis, Characterization and Biological Screening of Some Heterocyclic Compounds
PRATAPSINHA B. GOREPATIL 9
Keeping this object in mind the synthetic work for obtaining known and new
bioactive heterocycles and their precursors have been carried. While constructing the
molecules, successful attempts have been made to provide modified convenient and cost
effective synthetic routes for obtaining the required precursors and the desired products
with high yields.
Hence the present work entitled “Synthesis, characterization and biological
screening of some heterocyclic compounds” was undertaken and the details of the
synthetic work (carried using simple, efficient methods and also environmentally benign
green protocols like aqueous reaction media or nontoxic solvents, one pot synthesis and
reusable heterogeneous catalyst), characterizations of the intermediates and desired
products have been presented in the forthcoming four chapters of this thesis.
Synthesis, Characterization and Biological Screening of Some Heterocyclic Compounds
PRATAPSINHA B. GOREPATIL 10
References and notes:
1. Meth-Cohn O. Comprehensive Heterocyclic chemistry, Vol. 1, Pergamon
press, Oxford, 1984.
2. Czarnik A. W. Acc. Chem. Res. 1996, 29, 112.
3. Clough J. M. and Godfref C. R. A. Chem. Br. 1995, 466.
4. Dahiya R., Kumar A. and Yadav R. Molecules, 2008, 13, 958.
5. Arvanitis A., Rescinito J. T., Arnold C. R., Wilde R. G., Cain G. A., Sun J. H.,
Yan J.-S., Teleha C. A., Fitzgerald L. W., McElroy J., Zaczek R., Hartig P. R.,
Grossman S., Arneric S. P., Gilligan P. J., Olson R. E., Robertson D. W.
Bioorg. Med. Chem. Lett. 2003, 13, 125.
6. Tsutsui H., Narasaka K. Chem. Lett. 1999, 45.
7. (a) Katritzky A. R., Ramsden C. A., Scriven E. F. V., Taylor R. J. K.
Comprehensive Heterocyclic Chemistry III; Eds.; Pergamon: Oxford, New
York, USA, 2008, Vol. 4. (b) Katritzky A. R., Pozharskii A. F. Handbook of
Heterocyclic Chemistry, 2nd ed.; Pergamon: Oxford, UK, 2000.
8. Chen C., Chen Y.-J. Tetrahedron Lett. 2004, 45, 113.
9. (a) Zhang Y., Tocchetti C. G., Krieg T., Moens A. L. Free Radical Biol. Med.
2012, 53, 1531. (b) Dumont M., Beal M. F. Free Radical Biol. Med. 2011, 51,
1014. (c) Al Ghouleh I., Khoo N. K., Knaus U. G., Griendling K. K., Touyz
R. M., Thannickal V. J., Barchowsky A., Nauseef W. M., Kelley E. E., Bauer
P. M., Darley-Usmar V., Shiva S., Cifuentes-Pagano E., Freeman B. A.,
Gladwin M. T., Pagano P. J. Free Radical Biol. Med. 2011, 51, 1271. (d)
Wang H. Y., Chen G., Xu X. P., Ji S. J. Synth. Met. 2010, 160, 1065.
10. (a) Park M. J., Kwak J., Lee J., Jung I. H., Kong H., Lee C., Hwang D. H.,
Shim H. K. Macromolecules, 2010, 43, 1379. (b) Yao S., Ahn H. Y., Wang
X., Fu J., van Stryland E. W., Hagan D. J., Belfield K. D. J. Org. Chem. 2010,
75, 3965. (c) Cressier D., Prouillac C., Hernandez P., Amourette C., Diserbo
M., Lion C., Rima G. Bioorg. Med. Chem. 2009, 17, 5275. (d) Esashika K.,
Yoshizawa-Fujita M., Takeoka Y., Rikukawa M. Synth. Met. 2009, 159, 2184.
Synthesis, Characterization and Biological Screening of Some Heterocyclic Compounds
PRATAPSINHA B. GOREPATIL 11
(e) Sun Y., Duan L., Wei P., Qiao J., Dong G., Wang L., Qiu Y. Org. Lett.
2009, 11, 2069. (f) Zajac M., Hornbarik P., Magdolen P., Foltinova P.,
Zaharadnik P. Tetrahedron, 2008, 64, 10605. (g) Bahrami K., Khodaei M. M.,
Naali F. J. Org. Chem. 2008, 73, 6835.
11. (a) Gabriel N. V., Maria de Monserrat R. V., Lilian Y. M., Victor M., Lucia
G., Alicia H. C., Rafael C., Francisco H. L. Eur. J. Med. Chem. 2006, 41, 135.
(b) Lion C. J., Matthews C. S., Wells G., Bradshaw T. D., Stevens M. F. G.,
Westwell A. D. Bioorg. Med. Chem. 2006, 16, 5005. (c) VanVliet D. S.,
Gillespie P., Scicinski J. J. Tetrahedron Lett. 2005, 46, 6741. (d) Gabriel N.
V., Roberto C., Alicia H. C., Lilian Y., Francisco H. L., Juan V., Raul M.,
Rafael C., Manuel H., Rafael C. Bioorg. Med. Chem. Lett. 2001, 11, 187. (e)
Fonseca T., Gigante B., Gilchrist T. L. Tetrahedron 2001, 57, 1793. (f)
Bougrin K., Loupy A., Petit A., Daou B., Soufiaoui M. Tetrahedron, 2001, 57,
163. (g) Kamitori Y. Tetrahedron Lett. 2000, 41, 9267. (h) Chu Q. L., Wang
Y. L., Zhu S. Z. Synth. Commun. 2000, 30, 677.
12. Vicni P., Geronikaki A., Incerti M., Busonera B., Poni G., Cabras C. A., Colla
P. L. Bioorg. Med. Chem. 2003, 11, 4785. (b) Burkholder C. R., Dolbier W.
R. Jr., Medebielle M. J. Fluorine Chem. 2001, 109, 39. (c) Billard T., Langlois
B. R., Medebielle M. Tetrahedron Lett. 2001, 42, 3463. (d) Burkholder C. R.,
Dolbier W. R. Jr., Medebielle M. J. Fluorine Chem. 2000, 102, 369.
13. Spasov A. A., Yozhitsa I. N., Bugaeva L. I., Anisimova V. A. Pharm. Chem.
J. 1999, 33, 232. (b) Commandeur J. N. M., King L. J., Koymans L.,
Vermeulen N. P. E. Chem. Res. Toxicol. 1996, 9, 1092.
14. Spasov A. A., Yozhitsa I. N., Bugaeva L. I., Anisimova V. A. Pharm. Chem.
J. 1999, 33, 232.
15. Kim J. S., Gatto B., Yu C., Liu A., Liu L. F., LaVoie E. J. J. Med. Chem.
1996, 39 992.
16. Roth T., Morningstar M. L., Boyer P. L., Hughes S. H., Buckheit R. W. Jr.,
Michejda C. J. J. Med. Chem. 1997, 40, 4199.
Synthesis, Characterization and Biological Screening of Some Heterocyclic Compounds
PRATAPSINHA B. GOREPATIL 12
17. Hutchinson I., Bradshaw T. D., Matthews C. S., Stevens M. F. G., Westwell
A. D., Bioorg. Med. Chem. Lett. 2003, 13, 471.
18. Huang S. -T., Hsei I. -J., Chen C. Bioorg. Med. Chem. Lett. 2006, 14, 6106.
19. Alaimo R. J., Pelosi S. S., Freedman R. J. Pharm. Sci. 1978, 67, 281.
20. Figge A., Altenbach H. J., Brauer D. J., Tielmann P. Tetrahedron: Asymmetry,
2002, 13, 137.
21. Costa S. P. G., Batista R. M. F., Cardoso P., Belsley M., Raposo M. M. M.
Eur. J. Org. Chem. 2006, 3938.
22. Day J. C., Tisi L. C., Bailey M. J. Luminescence, 2004, 19, 8.
23. Batista R. M. F., Costa S. P. G., Raposo M. M. M. Tetrahedron Lett. 2004, 45,
2825.
24. Clark J. H. Green Chemistry, 1999, 1, 1.
25. Noyori R. Chem. Comm. 2005, 14, 1807.
26. (a) Sheldon R. A. Acad. Sci., Ser. IIc: Chim. 2000, 3, 541. (b) Sheldon, R. A.
Chem. Ind., (London, U. K.) 1997, 12.
27. Trost B. M. Science, 1991, 254, 1471.
28. Trost B. M. Science, 1983, 219, 245.
29. Song J. J., Reeves J. T., Fandrick D. R., Tan Z., Yee N. K., Senanayake C. H.
Green Chem. Lett. Rev. 2008, 1, 141.
30. Anastas P. T., Beach E. S. Green Chem. Lett. Rev. 2007, 1, 9.
31. Bienayme, H.; Hulme, C.; Oddon, G.; Schmitt, P. Chem. Eur. J. 2000, 6,
3321.
32. (a) Cariou C. C. A., Clarkson G. J., Shipman M. J. Org. Chem. 2008, 73,
9762. (b) Zhou L., Bohle D. S., Jiang H. F., Li C. J. Synlett, 2009, 937. (c)
Mukhopadhyay C., Tapaswi P. K., Drew M. G. B. Tetrahedron Lett. 2010, 51,
3944. (d) Kumaravel K., Vasuki G. Curr. Org. Chem. 2009, 13, 1820. (e)
Brauch S., Gabriel L., Westermann B. Chem. Commun. 2010, 46, 3387.
33. (a) Elders N., van der Born D., Hendrickx L. J. D., Timmer B. J. J., Krause A.,
Janssen E., de Kanter F. J. J., Ruijter E., Orru R. V. A. Angew. Chem., Int. Ed.
Synthesis, Characterization and Biological Screening of Some Heterocyclic Compounds
PRATAPSINHA B. GOREPATIL 13
2009, 48, 5856. (b) Bonfield E. R., Li C. J. Adv. Synth. Catal. 2008, 350, 370.
(c) Domling A. Chem. Rev. 2006, 106, 17. (d) Ramon, D. J., Yus M. Angew.
Chem., Int. Ed. 2005, 44, 1602. (e) Domling A., Ugi I. Angew. Chem., Int. Ed.
2000, 39, 3168. (f) Zhu J., Eur. J. Org. Chem. 2003, 1133. (g) Chapman C. J.,
Frost C. G. Synthesis, 2007, 1.
34. (a) Lieby-Muller F., Simon C., Constantieux T., Rodriguez J. QSAR Comb.
Sci. 2006, 25, 432. (b) Sharma G. V. M., Reddy K. L., Lakshmi P. S., Krishna
P. R. Synthesis, 2006, 1, 55. (c) Wang L. M., Sheng J., Zhang L., Han J. W.,
Fan Z. Y., Tian H., Qian C. T. Tetrahedron, 2005, 61, 1539.
35. Hashem S., Mona H. S., Fatemeh M. Can. J. Chem. 2008, 86, 1044.
36. Srinivas U., Srinivas Ch., Narender P., Rao V. J., Palaniappan S. Catal.
Commun. 2007, 8, 107.
37. Heravi M. M., Tajbakhsh M., Ahmadi A. N., Mohajerani B. Monatshefte fur
Chemie, 2006, 137, 175.
38. Mobinikhaledi A., Forughifar N., Zendehdel M., Jabbarpour M. Synth. React.
Inorg. Met.-Org. Nano-Metal Chem. 2008, 38, 390.
39. Kumar A., Maurya R. A., Ahmad P. J. Comb. Chem. 2009, 11, 198.
40. Sharghi H., Asemani O., Tabaei S. M. H. J. Heterocycl. Chem. 2008, 45,
1293.
41. Sharghi H., Aberi M., Doroodmand M. M. Adv. Synth. Catal. 2008, 350,
2380.
42. Khan A. T., Parvin T., Choudhury L. H. Synth. Commun. 2009, 39, 2339.
43. Maiti D. K., Halder S., Pandit P., Chatterjee N., De J. D., Pramanik N., Saima
Y., Patra A., Maiti P. K. J. Org. Chem. 2009, 74, 8086.
44. Ruiz R., Corma A., Sabater M. J. Tetrahedron, 2010, 66, 730.
45. Chari M. A., Shobha D., Zaidi S. M. J., Reddy B. V. S., Vinu A. Tetrahedron
Lett. 2010, 51, 5195.
46. Jin H., Xu X., Gao J., Zhong J., Wang Y. Adv. Synth. Catal. 2010, 352, 347.
Synthesis, Characterization and Biological Screening of Some Heterocyclic Compounds
PRATAPSINHA B. GOREPATIL 14
47. (a) Vinu A., Srinivasu P., Miyahara M., Ariga K. J. Phys. Chem. B 2006, 110,
801. (b) Vinu A., Hossain K. Z., Satish Kumar G., Ariga K. Carbon, 2006, 44,
530. ( (d) Chari M. A., Syamasundar K. Catal. Commun. 2005, 6, 67.
48. (a) Palmer A. M., Zanotti-Gerosa A. Current Opinion in Drug Discovery and
Development 2010, 13, 698. (b) Shang G., Li W., Zhang X. Transition Metal-
Catalyzed Homogeneous Asymmetric Hydrogenation, in: Catalytic
Asymmetric Synthesis, 3rd edn., (Ed.: I. Ojima), Wiley, Hoboken, 2010, 343.
(c) Lennon I. C., Moran P. H. Current Opinion in Drug Discovery and
Development, 2003, 61, 855. (d) Blaser H.-U., Malan C., Pugin B., Spindler
F., Steine H., Studer M. Adv. Synth. Catal. 2003, 345, 103.
49. (a) Longmire L. M., Wang B., Zhang X. J. Am. Chem. Soc. 2002, 124, 13400.
(b) Agbodjan A. A., Cooley B. E., Copley R. C. B., Corfield J. A., Flanagan
R. C., Glover B. N., Guidetti R., Haigh D., Howes P. D., Jackson M. M.,
Matsuoka R. T., Medhurst K. J., Millar A., Sharp M. J., Slater M. J., Toczko J.
F., Xie S. J. Org. Chem. 2008, 73, 3094.
50. (a) Ivin K. J., Mol J. C., Olefin Metathesis and Metathesis Polymerisation,
Academic Press, San Diego, 1997. (b) Reuben B., Wlttcoff H. J. Chem. Educ.
1988, 65, 605. (c) Magano J., Dunetz J. R. Chem. Rev. 2011, 111, 2177.
51. Handbook of Metathesis, (Ed.: R. H. Grubbs), Wiley- VCH, Weinheim, 2003.
52. Bonrath W., Letinois U., Netscher T., Schutz J. in: Mizoroki-Heck Reaction,
(Ed.: M. Oestreich), John Wiley and Sons Ltd., Chichester, UK, 2009.
53. Negishi E.-I., Hu Q., Huang Z., Wang G., Yin N. in: Chemistry of Organozinc
Compounds, (Part-I), (Eds.: Z. Rappoport, I. Marek), John Wiley and Sons
Ltd., Chichester, UK, 2006.
54. (a) Christmann U., Vilar R. Angew. Chem. 2005, 117, 370. (b) Christmann U.,
Vilar R. Angew. Chem. 2005, 44, 366. (c) Alonso F., Beletskaya I. P., Yus M.
Tetrahedron, 2008, 64, 3047. (d) Metal-Catalyzed Cross-Coupling Reactions,
Vol. 2, (Eds.: A. de Meijere F. Diederich), Wiley-VCH, Weinheim, 2004. (k)
Synthesis, Characterization and Biological Screening of Some Heterocyclic Compounds
PRATAPSINHA B. GOREPATIL 15
Modern Arylation Methods, (Ed.: L. Ackermann), Wiley-VCH, Weinheim,
2009.
55. (a) Hartwig J. F. Nature, 2008, 455, 314. (b) Surry D. S., Buchwald S. L.
Chem. Sci. 2011, 2, 27.
56. Anon, Chirality, 1992, 4, 338.
57. Farina V., Reeves J. T., Senanayake C. H., Song J. J. Chem. Rev. 2006, 106,
2734.