AFM, SPM
A. Green Lee
3. Advanced Methods of Organic Synthesis: Plenary lecture PL-8 APPROACHES TO THE SYNTHESIS OF SOME
BIOLOGICALLY ACTIVE COMPOUNDS
The University of Manchester, The School of Chemistry, Manchester, UK
A. Green
3. Advanced Methods of Organic Synthesis: Plenary lecture PL-9 THE NATURE OF THE CATALYST IN TRANSITION- METAL-CATALYZED CARBON-HETEROATOM AND
CARBON-CARBON BONDS FORMATION REACTION
Zelinsky Institute of Organic Chemistry, Moscow, Russia V.P. Ananikov val@ioc.ac.ru
Recently we have developed a series of catalytic reactions to accomplish carbon- heteroatom (C-I, C-P, C-S, and C-Se) bonds formation reactions leading to functionalized alkenes and carbon-carbon (C-C) bond formation as a route to functionalized dienes [1].
The synthetic approach involves atom-economic addition reactions of easily available regents – alkynes, thiols, disulfides, diselenides, iodine, and H-phosphonates. Transition metal catalysts furnish multistep highly regio- and stereoselective transformations under mild conditions, thus resulting in design of practical one-pot procedures.
The question of principal importance is the nature of catalytic transition metal species. Our mechanistic NMR, ESI-MS studies and theoretical [1] showed that homogeneous and nanoparticle catalysts may both be present under studied conditions and connected by leaching/agglomeration. The techniques will be presented and discussed to distinguish the metal species under catalytic conditions and to determine their role in the reaction.
Complex nature of catalyst active centers interconversion between different metal complexes and particles points out for supramolecular organization of catalytic systems in solution.
References:
[1] (a) Chem. Rev., 2011, 111, 1596; (b) Dalton Trans., 2011, 40, 4011; (c) Curr. Org. Synth., 2011, 8, 2; (d) Chem. Asian J. 2011, 6, 306; (e) J. Organomet. Chem. 2011, 696, 400; (f) Chem. Eur. J. 2010, 16, 2063; (g) Adv. Synth. Catal. 2010, 352, 2979; (h) Organometallics 2010, 29, 5098; (i) Mendeleev Commun.
2010, 20, 125; (j) J. Mol. Cat. A: Chem. 2010, 324, 104; (k) Eur. J. Inorg. Chem. 2009, 1149; (l) Chem.
Eur. J. 2008, 14, 2420; (m) J. Am. Chem. Soc. 2007, 129, 7252; (n) J.Am.Chem.Soc, 2002, 124, 2839.
3. Advanced Methods of Organic Synthesis: Plenary lecture PL-10 MULTIPLE Pd-CATALYZED TRANSFORMATIONS
FOR THE SYNTHESIS OF NATURAL PRODUCTS, DRUGS AND MATERIALS
Institute of Organic and Biomolecular Chemistry, Georg-August- University Gottingen, Gottingen, Germany
L.F. Tietze ltietze@gwdg.de
The development of novel highly efficient procedures for the synthesis of natural products, drugs, agrochemicals and materials is an important topic in academic and industrial chemistry.
These procedures must not only be compatible with our environment and allow the preservation of our resources but they should also have economical advantages. In such an approach the proportion of the number of steps and the increase of complexity is a valuable standard for the quality of a synthesis.
A general way to improve synthetic efficiency and also address the above mentioned criteria is the design of multiple transition metal catalyzed transformations either in a sequential or a domino fashion. This methodology allows the formation of complex compounds starting from simple substrates in very few steps.1
α-Tocopherol HO
O
8ґ 4ґ
2
Molecular Switches O
O OH O
O
O
O O H
H H
H O MeO OMe MeO
O NMe
2
Spinosyn A
Desogestrel
O
OH OH
OH O OH
Diversonol OH
H H
H H
In the lecture the use of multiple Pd-catalyzed transformations for the efficient synthesis of α-tocopherol2, spinosyns3, steroids4, diversonol5 and molecular switches6 will be presented.
References:
(1) a) Tietze, L. F.; Brasche, G.; Gericke, K. Domino Reactions in Organic Synthesis, Wiley VCH, Weinheim 2006;
b) Tietze, L. F. Chem. Rev. 1996, 96, 115–136; c) Tietze, L. F.; Beifuss, U. Angew. Chem. Int. Ed. Engl. 1993, 32, 131-163; d) Tietze, L. F.; Levy, L. The Mizoroki-Heck Reaction in Domino Processes in "The Mizoroki-Heck Reaction" (Ed.: M. Oestreich) Wiley-VCH, Chichester, 2009, p. 281-344; Tietze, L. F.; Düfert, A. Pure Appl.
Chem. 2011, 82, 1375-1392.
(2) Tietze, L. F.; Stecker, F.; Zinngrebe, J.; Sommer, K. M. Chem. Eur. J. 2006, 12, 8770-8776.
(3) Tietze, L. F.; Brasche, G.; Stadler, C.; Grube, A.; Böhnke, N. Angew. Chem., Int. Ed. 2006, 45, 5015-5018 and unpublished work.
(4) Tietze, L. F.; Krimmelbein, I. Chem. Eur. J. 2008, 14, 1541-1551.
(5) Tietze, L. F.; Spiegl, D. A.; Stecker, F.; Major, J.; Raith, C.; Grosse, C. Chem. Eur. J. 2008, 14, 8956-8963 and unpublished work.
(6) Tietze, L. F.; Düfert, A.; Lotz F.; Sölter, L.; Oum, K.; Lenzer, T.; Beck, T.; Herbst-Irmer, R. J. Am. Chem. Soc.
2009, 131, 17879-17884. Tietze, L. F.; Düfert, A.; Hungeland,T; Oum, K.; Lenzer, Chem. Eur. J. 2011, on line and unpublished work.
3. Advanced Methods of Organic Synthesis: Oral report O-13 DOPED π-CONJUGATED ORGANIC EMITTERS:
SYNTHESIS, PROPERTIES AND SUPRAMOLECULAR ORGANIZATION University of Namur (FUNDP), Department of Chemistry, Namur, Belgium
D. Bonifazi davide.bonifazi@fundp.ac.be
The development of organic-based polymers and of their hybrid derivatives paves the way to materials with a continuously tunable energy gap from the IR to the deep UV.
Specifically, there is a growing demand for light-emitting devices (LEDs) in the deep UV region, for a variety of applications where high photon energy is necessary for either processing or sensing/characterisation purposes (UV lamps for photodynamic therapy, water sterilization systems, "solar-blind" photodetectors, to name a few). A possible engineering strategy meeting these requirements would be to tune the electronic properties of the material by combining molecules with a similar carbon-based structures replacing every pair of carbon atoms rings by boron and nitrogen atoms. In this respect, borazine rings (Stock in 1926) are good candidates. However, the sensitivity toward water has hampered their exploitation in current technologies. In this report, we will describe the synthetic efforts toward the synthesis of water-stable borazine derivatives. Fluorescence studies in solution and at the solid state showed the presence of a strong UV-emission band in the UV region (300 nm, Φ = 7.5%). The synthesis of unprecedent unsymmetrical borazine derivatives and borazene linear modules will be shown as well. Novel H-bonding interactions involving boronic acids will be also discussed showing their potentials as alternative molecular synthones in molecular recognitions.
References:
Unpublished results; S. Kervyn and D. Bonifazi, EU patent EP11158909, filed 18.3.2011, pending ; Pure Appl. Chem., 2011, 83, 899-912 ; L. Maggini and D. Bonifazi* Chem. Soc. Rev. 2011, DOI:10.1039/C1CS15031F ; S. Mohnani and D. Bonifazi* Coord. Chem. Rev., 2010, 254, 2342- 2362. D. Bonifazi,* S. Mohnani and A. Llanes-Pallas Chem. Eur. J., 2009, 15, 7004-7015.
3. Advanced Methods of Organic Synthesis: Oral report O-14 SYNTHESIS OF CYCLIC PEROXIDES
N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, Russia
A.O. Terentyev terentev@ioc.ac.ru
In the past two decades, organic peroxides have come to the attention of chemists and researchers in the field of drug design because certain representatives of these compounds exhibit antimalarial and antitumor activities. This has stimulated the development of methods for the synthesis of these compounds.
Nowadays, cyclic compounds, such as tetraoxanes, ozonides, and trioxanes, are considered as the most promising synthetic peroxides having such activities. Some of these compounds exhibit high activity comparable to or higher than that of the natural peroxide artemisinin, which is widely used for the treatment of malaria. The design of explosives based on cyclic peroxides is of particular interest. For example, triacetone triperoxide is one of the most sensitive known explosives, whose power is similar to that of trinitrotoluene.
This report describes the synthesis of cyclic organic, organosilicon and organogermanium peroxides.
O O O O R3 R2 R1 R2
R1
O O O O
R3 R4
O O
O O O
O 9 R3
R4
R2 R1 R1 R2
O O
O O Si O O 9
R3 R4
R2
R1 R1 R2
O O
O O Ge O O 9
R3 R4
R2
R1 R1 R2 R2
R1
O O O O
Si R3
R4 O
O O O SiR3
R4
R1 R2
R1 R2 7
This work is supported by the Program for Support of Leading Scientific Schools of the Russian Federation (Grant NSh 4945.2010.3) and the Grant of the Russian Foundation for Basic Research (Grant 11-03-00857-a).
3. Advanced Methods of Organic Synthesis: Oral report O-15 CYCLIZATION OF FUNCTIONALIZED (BUTA-1,3- DIYNYL)ARENES IN THE SYNTHESIS OF ENDIYNE
SYSTEMS FUSED TO HETEROCYCLES Saint-Petersburg State University, Department of Chemistry, Saint-Petersburg, Russia
I.A. Balova irinabalova@pobox.spbu.ru
Enediyne antitumor antibiotics, belonging to a small family of natural compounds, are among the most potent antineoplastic agents ever discovered1. Natural enediynes are too scarce for practical use, additionally, have low antitumor selectivity, therefore, there is a significant interest in developing syntheses of artificial enediyne compounds.
Heterocycles possessing an enediyne system are promising objects for the investigation of general patterns of action and structure-activity relationships. However there is no general method to construct (Z)-3-ene-1,5-diyne system attached to a variety of heterocycles. Reported syntheses of such systems usually include transformation of functional groups to the ethynyl moieties or double cross-coupling of terminal acetylenes with dihaloheteroarenes,which are not widely accessible.
Recently we demonstrated the cyclization of ortho-functionalized (buta-1,3-diynyl)arenes to be a short route towards heterocycles, having ethynyl moieties and halogen at neighboring atoms2,3. This cyclization and followed Pd/Cu catalyzed cross-coupling with terminal acetylenes is promising approach to enediyne systems fused to various heterocycles. Moreover this synthetic methodology can get these connections to advance clearly defined position of substituents at both triple bonds which is important for further enediynes modification.
The proposed methodology for obtaining of cinnolines, benzannulated S,N,O-five- membered heterocycles, isocumarines will be discussed as well as examples of enediyne systems synthesis.
References:
1. K.C. Nicolaou, G. Zuccarello, C. Riemer, V.A. Estevez, W.M. Dai. J. Am. Chem. Soc., 1992, 114, 7360; R.-G. Shao. Curr. Mol. Pharm., 2008, 1, 50.
2. O. V. Vinogradova, V. N. Sorokoumov, I. A. Balova. Tetrahedron Lett. 2009, 6358.
3. N. A. Danilkina,S. Bräse, I. A. Balova. Synlett, 2011, 517.
This project is supported by Saint-Petersburg State University (grants 12.38.14.2011, 12.41.246.2011 ) and RFBR (grant 11-03-00048-а).
3. Advanced Methods of Organic Synthesis: Oral report O-16 SYNTHESIS, INTRA- AND INTERMOLECULAR
TRANSFORMATIONS OF N-AMINOAZIRIDINE DERIVATIVES
Saint-Petersburg State University, Organic Chemistry Department, Saint-Petersburg, Russia
M.A. Kuznetsov A.S. Pankova
V.V. Voronin mak@mail.wplus.net
Oxidative addition of various N-aminoheterocycles to diverse unsaturated compounds is a general way to prepare a wide range of N-aminoaziridine derivatives. We have shown recently that, along with a traditionally used N-aminophthalimide (API) and 3-aminoquinazolinones, the easily available unsaturated cage N-aminoimides can be used in this reaction successfully, affording the corresponding N-aminoaziridines in good yields.
API oxidation in the presence of different 5-membered aromatic alkenylheterocycles (pyrazoles, 1,2,4- and 1,3,4-oxadiazoles, thiophenes) leads to adducts on exocyclic double bonds, aziridinylheterocycles. But furanes (both with alkenyl substituents, and without them) provide 5-membered ring opening products – (Z)-alk-2-en-1,4-diones monohydrazones – under the same conditions. The very special case is the oxidative addition of API to thiophene and selenophene, that provides bis-adducts, trans-fused 5- thia(seleno)-3,7-diazatricyclo[4.1.0.02,4]heptanes, only.
A strained three-membered ring causes a high activity of aziridines, and most of its transformations include a cleavage of C-N bonds or C-C bond (the latter one leads to octet- stabilized 1,3-dipoles, azomethyne ylides) for strain energy relief. As a result, the heating of N-aminoaziridine derivatives can cause its isomerization to corresponding hydrazones and imines. Thermolysis of aziridines with unsaturated substituents (>C=C<, >C=O, -N=N-) on carbon atoms leads to pyrrolines, 1,3-oxazoles and 1,2,3-triazoles. Intra- and intermolecular 1,3-dipolar cycloaddition of intermediate azomethine ylides on C=C, C≡C, and even C≡N bonds gives the corresponding 5-membered nitrogen heterocycles and polycyclic compounds.
3. Advanced Methods of Organic Synthesis: Oral report O-17 CHEMISTRY OF STERICALLY HINDERED O-QUINONES. FUNCTIONALIZATION WITH
ANNELATED DITHIOL, THIAZOLE, IMIDAZOLE AND TETRATHIAFULVALENE MOIETIES
G.A. Razuvaev Institute of Organometallic Chemistry of RAS, Nizhny Novgorod, Russia
V.A. Kuropatov viach@iomc.ras.ru
o-Quinone is a stronger acceptor as compared with p-quinone, in addition it can act as a chelating ligand to form stable complexes with various transition and non-transition metals. Moreover, transition metals in such complexes can change their oxidation state when the metal environment is altered. Modification of quinone skeleton is required to tune steric and redox characteristics, or to add auxiliary functionalities such as coordination sites or redox active centers.
We have studied 1,4-addition and substitution reactions in 3,6-di-tert-butyl-o- quinones and developed the methods for selective preparation of o-quinones annelated with 1,3-imidazole, thiazole, dithiole and dithiete ring. A variety of functionalized o-quinone derivatives have been synthesized. Several of these compounds such as TTF and dithiete derivatives are promising as bridging and redox amphotheric ligands
t-Bu
t-Bu O
O (X)
S S
t-Bu t-Bu
O S O
S t-Bu
t-Bu O
O
NR NR t-Bu
t-Bu
Z O
O
NR S
t-Bu
t-Bu Z
O
O S
S t-Bu
t-Bu
Z O
O S
S
t-Bu t-Bu
O O
R=H, Ph, Me; Z=O, NH, N+R2
Synthetic methods used in preparation of these compounds do not require complicated protection-deprotection procedures. Chemical properties of new quinones and their reduced and oxidized forms will be discussed.
We gratefully acknowledge the financial support of the Russian Foundation for Basic Research, grant 10-03-00788-a and the Program for support of Leading Scientific Schools NSh-7065.2010.3.
This work was made according to FSP “Scientific and scientific-pedagogical cadres of innovation Russia” for 2009–2013 years (GK-P839 from 25.05.2010).
3. Advanced Methods of Organic Synthesis: Oral report O-18 SYNTHESIS OF SULTAMS BY CYCLOALKYLATION
OF ALPHA-SUBSTITUTED METHANESULFONAMIDES St. Perersburg State University, Department of Chemistry, St. Petersburg, Russia
V.V. Sokolov vsokolo@mail.ru
Acyclic sulfonamides can commonly be prepared by sulfonylation of amines, but synthesis of sultams is not so easy. One of the possible solutions is the intramolecular cycloalkylation (arylation) of sulfonamides. In this connection sulfonamides bearing an additional C-nucleophilic center possess obvious potential.
EWG SO2Cl N S
O O EWG Ar
N S
O O
Ar
S N Ar
O O EWG
N I PMB
S O O
EWG S
N O
O EWG
I N S PMP
O O
EWG
S N
O EWGO EWG
( )n
( )n N S
( )m MeO2C
O O
( )n
( )n
n = 1−3 n = 1, 2
n = 1, 2
n = 1, 2; m = 1−3 EWG = MeOCO, Ar
PMB PMP
Therein we report intermolecular cycloalkylations of (methoxycarbonyl)methanesulfonanilides in K2CO3/DMF system and α-
toluenesulfonamides under wide range of the conditions by 1,ω-dihaloalkanes to give monocyclic sultams with various ring sizes. The intramolecular variant of the same reaction allows to obtain bicyclic sultams with sulfonylcyclopropane moiety.
For all the obtained sultams 4-methoxyphenyl (PMP) or 4-methoxybenzyl (PMB) group was removed from the nitrogen with CAN under mild condition. To the best of our knowledge, there have been no reports concerning the analogous cleavage of N-PMP- sulfonamides.
The cycloalkylation of the sultams bearing a secondary amide function leads to bicyclic compounds with the sulfur atom in the apex position. At the present time in literature only one sultam from this new class is represented. Our method shows a possibility to create a wide range of different bicyclic systems based on simple variations of the alkylation agents and starting material.
The intramolecular C-arylation of (methoxycarbonyl)methanesulfonamides with Pd(OAc)2/Ph3P/NaH allowed to synthesize benzo-annelated sultams.
3. Advanced Methods of Organic Synthesis: Oral report O-19 3,4-DICHLORO-2(5H)-FURANONES: USEFUL
SYNTHONS FOR THE PREPARATION OF A VARIETY OF O-, N- AND S-HETEROCYCLES 1 - A.M. Butlerov Chemical Institute, Kazan Federal University, Kazan, Russia
2 - A.E. Arbuzov Institute of Organic and Physical Chemistry, Russian Academy of Sciences, Kazan, Russia
A.R. Kurbangalieva1 A.S. Ezhova1 O.A. Lodochnikova2