Organic Chemistry from the Eastern Bloc · PDF fileBaran Lab GM Organic Chemistry from the...
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Organic Chemistry from the Eastern Bloc Baran Lab GM 08/13/2011 Florina Voica Major Research Centers: Institute of Organic Chemistry, Polish Academy of Sciences Univ of Warsaw Adam Mickiewiecz Univ, Poznan Warsaw Univ of Technology Gdansk Technical Univ Founding fathers: Osman Achmatowicz (1899-1988) - alkaloids isolation (O. Achmatowicz Jr - sugar chemistry, name rxn) Jerzy Suszko (1889-1972) - polycyclic aromatics Edwin Plazek - heterocyclic chemistry Henryk Kuczynski (1909-1991) - terpene chemistry O OSitBuPh 2 H TMS SO 2 Ph nBuLi then MsCl 86% (over 2 steps) TMS PhO 2 S OSitBuPh 2 OMs dr 3:1 PhO 2 S OSitBuPh 2 TMS LDA, THF 89% TBAF 41% OH Tet. Lett. 1991, 32, 531 SO 2 Ph O TMS nBuLi, then HClO 4 , MeOH OH OH O (+)DET, Ti(OiPr) 4 , TBHP 1. TsCl, pyr 2. (nC 9 H 19 ) 2 CuLi C 9 H 19 O (+)-disparlure Tet. Lett. 1989, 30, 2845 O O Me Me O O Me O Me O H Me O OH 1. NaOMe, 40% 2. H 2 , Pd/SrSO 3 H 2 , Pd/C Me O H Me O OH H 1. L-selectride 2. N 2 H 4 3. I 2 Me H Me HO OH H I N 2 H 2 Me H Me HO OH H I Me H Me THPO OH H O Me 1. tBuNC, NaCNBH 3 Bu 3 SnCl, AIBN 2. DHP 3. MeLi, PhH Me H Me THPO OH H O O 1. LDA, MoOHPy 2. Ph 3 P • • O J. Org. Chem. 1988, 53, 4855 Prof. Jerzy Wicha - born on February 14, 1936, Warsaw, Poland; - education: M. Sc.: Moscow State University, 1958 Ph. D.: The University of Warsaw, 1964 D. Sc.: The University of Warsaw, 1970 - positions: 1958-1960 Research Associate, Institute of Pharmaceutical Industry, Warsaw 1960 -1970 Instructor - reader, the University of Warsaw 1970 - 1978 Docent, Institute of Organic Chemistry, Polish Academy of Sciences 1978 - Professor, the same Institute - 184 publications (Scifinder) - major research topics: steroid synthesis, some guanacastepene, prostaglandins research, some methods based on the Julia olefination reaction. Organic Chemistry from the Eastern Bloc Baran Lab GM 08/13/2011 Florina Voica Me Me H H THPO O Me Me H H THPO HO TMS Br TMS nBuLi, BF 3 •Et 2 O 93% Me Me H H THPO O TMS O O F 3 C O Me Me H H THPO O O Me Me H H THPO O OH OH Me Me OH H HO O O Digitoxigenin 1.VO(acac) 2 , TBHP, 86% 2. mCPBA, 87% 3. TFAA, pyr, 87% TBAF, H 2 O, THF, rt J. Org. Chem. 1995, 60, 1823 Me OMe Me CO 2 Et Me OMe Me EtO 2 C Br Br Br Me OMe Me Me Br Me OMe Me Me Br Br Br Me OMe Me Me Me Me Me Me Me HO LDA/THF, -78 °C then iPr 80% 1. DIBAL 2. TsCl, pyr 3. Superhydride 80% CHBr 3 -50%NaOH CETRIMID 50%, dr 1:1 (separable) MeLi/Et 2 O -78 °C to rt then MeI, -78 °C to rt 60% TsOH/aq dioxane 23-H-isocalysterol (both diastereoisomers are NPs) J. Am. Chem. Soc. 1995, 117, 1849 Organic Chemistry from the Eastern Bloc Baran Lab GM 08/13/2011 Florina Voica For more on steroid functionalization: J. Org. Chem. 2010, 75, 5388, J. Org. Chem. 1990, 55, 3484, Tetrahedron 1989, 45, 2223, Tet. Lett. 1988, 29, 4001, J. Org. Chem. 1973, 38, 1280. For some representative refs on formal syntheses of different vitamin Ds (20 papers published)- Tet. Lett. 1998, 29, 885, Synthesis 1999, 1209; J. Org. Chem. 2007, 72, 5276. For work on terpene synthesis: Tet. Lett. 2005, 46, 1149, J. Org. Chem. 2010, 75, 8337. Prof. Mieczyslaw Makosza - born in 1934 - education: M. Sc : Univ.of Leningrad, 1958 Ph.D : Technical Univ. Warsaw, 1956 D.Sc : Technical Univ. Warsaw, 1971 - positions: 1975-1977, Director, Institute of Organic Chemistry and Technology, Univ. of Warsaw 1979-present, Director, Institute of Organic Chemistry, Polish Academy of Sciences. - 420 publications (Scifinder) - major research areas: phase transfer catalysis (chemistry of carbanions and carbenes), vicarious nucleophilic substitution. Vicarious Nucleophilic Substitution of Hydrogen (VNS) - describes the reaction of a nucleophile with a electrophilic arene (nitroarenes, heteroarenes) or alkene; - the attack can occur ortho or para to the NO 2 group but there are ways to achieve selectivity; disubstituted prods are usually not observed; - VNS is an "umpolung Friedel-Crafts" reaction and it complements the scope of the FC rxn since it allows functionalization of arenes which are very poor nucleophiles in S E Ar. General reaction scheme: NO 2 X R Y base solvent + NO 2 - Y R X base -HX Y R NO 2 - NO 2 Y R H + Z = F, Cl, Br, I, OMe, OPh, SMe, Et, tBu, Ph, NMe 2 , CF 3 , CN, SO 2 Me, CO 2 H. Y (EWG) = SO 2 Ph, SO 2 NH 2 , CN, CO 2 Et, Cl, Ar etc. X (good LG) = Cl, Br, OPh, SPh etc. Typical base: KOH, NaOH, tBuOK. Typical solvent : DMSO, DMF, THF, MeOH, NH 3 (l). Extensive reviews on the topic: Acc. Chem. Res. 1987, 20, 282; Synthesis 1991, 103; Chem. Soc. Rev. 2010, 39, 2855; for VNS examples on electrophilic olefins: Tetrahedron 1991, 47, 5001; for an exhaustive review on VNS on heterocycles: Chem. Rev. 2004, 104, 2631. NO 2 NC Me Ph + OH Me Ph NC tBuOK DMF/THF -70 °C DMDO, H 2 O aq. NH 4 Cl 83% J. Org. Chem. 1998, 63, 4390 N N N N SO 2 Ph N N SO 2 Ph SO 2 Ph Cl SO 2 Ph KOH, DMSO 66% OH MeO NO 2 NO 2 Synthesis 1997, 1131 OH MeO NO 2 NO 2 CN OMe MeO NO 2 NO 2 CN OMe MeO NO 2 NO 2 CN CO 2 Et PhO CN tBuOK, DMF 80% Me 2 SO 4 , NaHCO 3 83% Br CO 2 Et 69% H N HN O OMe MeO H 2 , PdCl 2 -Fe 48% H N HN O O O Damirone B Chem. Lett. 1987, 61 NO 2 N Me SO 2 Ph N Me SO 2 N + Ph TBSO O - N Me SO 2 Ph NO N Me SO 2 Ph N TBSO N N Me SO 2 TBSO N N Me SO 2 DBU TBSCl DBU -TBSOH DBU TBSCl hν DBU -TBSOH Acta Chem. Scand. 1992, 46, 689 Organic Chemistry from the Eastern Bloc Baran Lab GM 08/13/2011 Florina Voica Phase transfer catalysis: A process in which a phase transfer catalyst (usually a tetraalkylammonium salt, QX ++ ) facilitates the reaction of inorganic and organic anions or carbenes with organic electrophiles. Practically, it consists of a two-phase mixture: the inorganic solution containing reacting anions or base that will generate organic anions; the organic mixture containg the organic reactants and the phase transfer catalyst (source of lipophilic cations). General reaction scheme: - reactive inorganic anions: Na + Y - aq + Q + X - org Na + Y - aq + Q + X - org Q + Y - org + RX Q + X - org + RY - in situ generated organic anions: PhCH 2 CN org + Na + OH - aq PhCH - CN org Na + int + H 2 O aq PhCH - CN org Na + int + Q + X - org PhCH - CN org Q + org + Na + X - aq PhCH - CN org Q + org + R-Xorg R Ph CN org + Q + X - org For a general review and applications see: Pure Appl. Chem. 2000, 72, 1399 and refs therein. N + OMe PMB Br - TMSCF 3 (1.2 equiv) KF (s) (1.5 quiv) Ph 3 SnF (0.3 equiv) DCM, rt, 24h 76% N OMe CF 3 PMB CAN (2.2 equiv) MeOH-H2O 4:1 90% N OMe CF 3 J. Org. Chem. 2007, 72, 5574 Andrzej Daniewski - Institute of Organic Chemistry, Polish Academy of Sciences - Hoffman-La Roche, NJ - 89 publications (Scifinder) - major research areas: synthesis of cardiotonic steroids, vitamin D, bioactive sesquiterpenes. Cl OMe O O O Me O O Me Cl O MeO O O Me OAc O N 2 MeO B 3 MeO Me O OH AcO O Me O OAc AcO AcO H MeO + Me OH HO HO H MeO O Me OH O H MeO O H Me H H MeO O H TsOAc Ac 2 O, 70% NaOH, MeOH BF 3 •Et 2 O acetone, then H 2 O 75% J. Org. Chem. 1975, 40, 3124, 3135 KOH, MeOH 80% 1. conc HCl 2. Ac 2 O, AcOH, 85% 3. chiral resolution 4. SOCl 2 5. CH 2 N 2 , 87% MeO O O O Me Me O MeO HBr, AcOH 14-dehydroequilenin O Me MeO O Me O MeO estrone 1. TiCl 4 2. Zn, 85% HClO 4 HBr Tet. Lett. 1982, 23, 2411 Organic Chemistry from the Eastern Bloc Baran Lab GM 08/13/2011 Florina Voica O Me O O Me i-Bu 2 AlO H O Me O H Br Me OH H O Me H OH Me H O Me OH Me HO tBuCu, DIBAL HMPA 57% 1. PDC, 65% 2. Wittig, 92% 3. LAH, 87% J. Org. Chem. 1988, 53, 5534 Br 2 Me O O Me O O H OH OTBS TBSO O H Me O H HO OAc H H OAc O Me O H H OAc OAc H H OAc Me OAc HO H H OAc Me OH H H Me O H OH tBuCu, DIBAL 70% 7 steps 1. mCPBA 2. Martin rgnt 90% 1. LAH 2. Ac 2 O 3. Martin rgnt 90% (3 steps) 1. N 2 H 4 , H 2 O 2 2. SeO 2 60% 1. Martin rgnt 2. KOH O Et Me O compactin Tet. Lett. 1990, 31, 5599 Prof. Janusz Jurczak - Ph.D, Institute of Organic Chemistry, Univ of Warsaw, 1970 - Post-doc, V. Prelog, ETH Zurich, 1971-1972 - Habilitation, Institute of Organic Chemistry, Univ of Warsaw, 1979 - Professor, Dept of Chemistry, Univ of Warsaw, 1991 - 457 publications (Scifinder) - major research areas: sugar chemistry, high-pressure rxns (Polish specialty), supramolecular chemistry (criptands). The case for high pressure DA reaction : - negative volume of activation (i.e. the volume occupied by the transition state is smaller than that of the reactants) - high pressure effects on the DA rxn: i) acceleration of the rxn ii) modification of regio- and diastereoselectivity iii) changes in chemical equilibria - equation describing rate dependency: δ ln k / δP = - δV / RT (k - rxn rate, P - pressure, V - transitions state volume, T - temp) - high pressure ~ 12-25 kbar - commonly used technique in industry and academic labs - cases when high pressure does the job: hindered dienes/dienophiles, LA/temp sensitive substrates, whenever you might want different product distribution. Synthesis 1979, 41; Chem. Commun. 1983, 540; Synthesis 1985, 928. OMe C 5 H 11 O + O OMe C 5 H 11 O O C 5 H 11 15-20kbar 50-65 °C, Et 2 O 28% 1. MoO 3 , 30%H 2 O 2 2. Ac 2 O, pyr 3. 10% Pd/C 24% overall J. Org. Chem. 1981, 46, 2230 OMe + H O Me NBocBzl O Me OMe NBocBzl H O Me OMe NBocBzl H 1. 15 kbar, 2% Eu(fod) 3 50 °C, Et 2 O 2. PPTS, rt, MeOH 80%, dr 16:1 major + J. Org. Chem. 1989, 54, 3759 purpurosamine B Organic Chemistry from the Eastern Bloc Baran Lab GM 08/13/2011 Florina Voica Prof. Marek Chmielewski - Institute of Organic Chemistry, Polish Academy of Sciences, Warsaw - 298 publications (Scifinder) - major research areas: sugar chemistry, β-lactam containing natural products, high pressure reactions, asymmetric reactions. O TMSO N • O + 1 equiv 3 equiv 1. CDCl 3 , rt, 1 atm, 6h, 42% 2. steps OTMS CCl 3 O O HO OH NBn N O Bn O OH HO J. Org. Chem. 1986, 51, 2395 Tet. Lett. 1987, 28, 3035 N + - O BnO F O O + N O O O OBn F CuI (0.1 equiv), TMG (2 equiv), ACN, 44% N O O OBn F N O OBn F OH F J. Org. Chem. 2011 ASAP Ezetimibe O Prof. Bogdan Marciniec - born 1941 - Ph. D, 1970, Adam Mickiewicz Univ, Poznan - Postdoc, 1971-1972, Kansas Univ - Habilitation, 1975, Adam Mickiewicz Univ, Poznan - Professor, 1986, Adam Mickiewicz Univ, Poznan - 298 publications (Scifinder) - major research areas: organosilicon chemistry , catalysis, macromolecular organosilicon structures. General reaction mechanism for the sylilative coupling of olefins with vinyl silanes: SiR 3 M H H SiR 3 H H M SiR 3 M H R 1 M R 1 H SiR 3 H H M H H R 1 H SiR 3 + SiR 3 R 1 R SiR 3 M = Ru, Rh, Co R = alkyl, aryl, alkoxy R 1 = alkyl, pheyl, OR, SiR 3 , -pyrrolidinone, carbazole Acc. Chem. Res. 2007, 40, 943 O O Si Si RuHClCO(PPh 3 ) 3 (1 mol%) 80 °C, 1h 85% Si O O Si Si O Si Si O Si TMSO + Si(OEt) 3 TMSO Si(OEt) 3 92% H 2 O/HCl 88% RuHCl(CO)(PCy3) (1 mol%) PhMe, 110 °C J. Org. Chem. 2005, 70, 370 Angew. Chem. Int. Ed. 2006, 45, 8180 Organic Chemistry from the Eastern Bloc Baran Lab GM 08/13/2011 Florina Voica Other accomplished polish chemists: -Prof. Tadeusz Jagodzinki - Technical Univ. of Szczecin - main research areas: synthesis and reactivity of thioamide derivatives of benzene and 5-membered heterocyles (Chem. Rev. 2003, 103, 197) - Prof. Maria Rozwadowska - Adam Michiewicz Univ, Poznan - main research areas: synthesis of isoquinoline alkaloids, chiral amines and sulfoxides. (Chem. Rev. 2004, 104, 3341) - Prof. Karol Grela - Institute of Organic Chemistry, Polish Academy of Sciences - main research areas: olefin metathesis. Main research centers: Univ of Ljublijana (first chem PhD 1920) National Institute of Chemistry, Ljubljiana Founding fathers: Fritz Pregl (1869-1930) - quantitative organic microanalysis Miha Tisler (1926-2001) - hetrocyclic chemistry Prof. Marko Zupan - born - Ph. D. 1974, Faculty of Chemistry and Chemical Technology, University of Ljubljana - Associate Professor, 1982-1987, University of Ljubljana - Professor, 1987-, University of Ljubljana - 233 publications (Scifinder) - main research areas: chemistry of halosubstituted organic molecules, fluorination of organic molecules ( Sarlah says... " [M. Zupan] was the first guy who started using XeF 2 in organic synthesis") Electrophilic fluorination with XeF 2 , CeSO 4 F F 3 C Br 1. Mg, Et 2 O 2. CS 2 3. XeF 2 F 3 C CF 3 77% Tet. Lett. 1990, 31, 3357 F F F XeF 2 105 °C, 2.5h 28% 42% 30% + + Bull. Chem. Soc. Jpn. 1986, 59, 1659 XeF 2 not an ideal fluorinating reagent... - no regioselectivity for aromatic substrates - olefin/aromatic ring substitution very important for reactivity... - strong oxidant, minimal FG tolerance - it usually requires an acid catalyst for activation - product distribution very sensitive to rxn conditions Ph Me O CsSO 4 F (1.1 equiv), ACN rt, 1.5 h 84% Ph F Me J. Org. Chem. 1992, 57, 5334 N N N F OSO 2 F + CsSO 4 F (2 equiv), rt cyclohexane 70% 30% Tet. Lett. 1990, 31, 775 N N Me Me O O CsSO 4 F (1.3 equiv) MeOH, 40 ° C F N N Me Me O O F F OMe 72% Tetrahedron 1990, 46, 3093 Electrophilic fluorination with N-F reagents (Selectfluor, Accufluor) N + N + Cl F Selectfluor N + N + F (BF 4 - ) 2 Accufluor O O Me Selectfluor solvent free 87% O O Me F Me O HO Me O O F Selectfluor (1.05 equiv) H 2 O, 60 °C 74% OEt OEt F Selectfluor solvent free 61% Tet. Lett. 2007, 48, 2671 Org. Lett. 2004, 6, 4973 Accufluor (1.1 equiv) ACN, 70 °C NHAc F F NHAc + 1 : 3 74% Chem. Commun. 1996, 2247 (BF 4 - ) 2 Organic Chemistry from the Eastern Bloc Baran Lab GM 08/13/2011 Florina Voica Main research centers: National Academy of Sciences, Kiev Kiev Polytechnic Institute Karkow National Univ Prof. Andrey A Fokin - Dept. of Organic Chemistry, Kiev Polytechnic Institute - 104 publications (Scifinder) - major research areas: nanodiamonds, cage structures, alkane functionalization, computational chemistry of radicals and radical cations. Br 50% NaOH/CBr 4 DCM, Et 3 BnNCl, 40 °C 37% 50% NaOH/CBr 4 DCM, Et 3 BnNCl, 40 °C 44% I NaOH, CHI 3 , rt, 24h 92% nPr Et Et I I NaOH, CHI 3 , rt, 24h 92% Br + 4 : 1 Angew. Chem. Int. Ed. 1998, 37, 1895; 1999, 38, 2786 O O S O NaH. DMSO 130 °C, 12h 96% p-TSA, DCM 96% Org. Lett. 2007, 9, 2541 O Me HO O H 2 SO 4 80 °C 65% MeMgBr 93% CF 3 CO 3 H TFA 80% Org. Lett. 2009, 11, 3068 Main research centers: National Academy of Sciences of Belarus Belorussian State Univ Founding fathers: too close to Russia, difficult to define.. Prof. Oleg Kulinkovich - born 1948 in Estonia - Ph. D, 1975, Belorussian State Univ, Minsk (prof. Tishchenko) - Professor, 1987, Belorussian State Univ, Minsk - 174 publications (Scifinder) - major research areas: development of cat and noncatalytic methods based on transformations of strained organic and organometallic compounds Kulinkovich reaction: R CO 2 Me R OH 1. EtMgBr (2 equiv) Ti(OiPr) 4 (5-10 mol%) Et 2 O, rt, 1h 2. 5% aq H 2 SO 4 , 5 °C 76-95% Synthesis, 1989, 234 Chem. Rev. 2003, 103, 2597 OH 8 OH 8 HO C 17 H 35 OH Me C 17 H 35 8 Me C 17 H 35 7 Me C 17 H 35 7 Me Me O 1. ethyl stearate (1 equiv) Ti(OiPr) 4 (1 equiv) C 6 H 10 MgBr (6 quiv) 2. H + , H 2 O N 2 H 4 , KOH, 190 °C 56% 1. P, I 2 150 °C 2. KOtBu, DMSO 1. MeCO 2 Et (1.4 equiv) Ti(OiPr) 4 (1.4 equiv) C 6 H 10 MgBr (7.1 equiv) 2. H + , H 2 O, 64% 3, 11 - dimethylnonacosan-2-one 3. KOH, THF, 67% Tet. Lett. 1998, 39, 1823 Me OH Me OH 2 1. Ti(OiPr) 5 (0.5 equiv) iPrMgBr (2 equiv), Et 2 O, rt 2. H + , H 2 O 72% Synlett 2003, 967 For more on red coupling, see Ian Young GM C 5 H 12 Organic Chemistry from the Eastern Bloc Baran Lab GM 08/13/2011 Florina Voica σ H complex vit D 3 metabolite Organic Chemistry from the Eastern Bloc Baran Lab GM 08/13/2011 Florina Voica The goal of this presentation is to offer a detailed perspective on the state of art in organic chemistry research in the major academic centers in former Eastern Bloc countries (Poland, Czech Republic, Slovakia, Hungary, Slovenia, Croatia, Serbia, Macedonia, Albania, Bulgaria, Romania, Moldova, Ukraine, Belarus, Lithuania, Latvia, Estonia). The analysis for each individual country consists in identifying the researchers who have made significant contributions to the field. Historic context: - The Eastern Bloc refers to the region in Europe which entered under Soviet influence after WWII (Yalta conferene, 1945); - These were communist countries, either directly reporting to Moscow, or having more "independent" communist regimes; - Under the strict, totalitarian policies, the economic development was "extensive rather than intensive", with chracteristic shortages of goods and minimal innovation; - After the fall of USSR (1989-1991), these countries adopted the free market economic model (and democratic governments), but in most cases the '90s remain a period of slow development (transition period/lost generation); - Nov 1993, The Maastricht Treaty established The European Union; - WIth the exception of Albania, Serbia, Montenegro, Croatia and Russia, all former communist countries are now part of the EU; General aspects: The scientist in society: During the almost half a century of soviet cultural influence, science and technology served an important part of national politics and identity. However, significant efforts were focused on pure science and theoretical research, with little practical applications or economic impact. The educational system "In spite of all the apparent shortcomings and faults, the Russian secondary schools seem to prepare the students relatively well for life and for higher education, especially in the sciences and mathematics. The intensity of the work and the student's motivation to succeed is a big factor. Admission to higher education is a crucial, life-long decision and it is made while the student in still in the secondary school." "In general, the Soviet Educators in higher educational institutions receive and work with a better motivated and selected student than their American counterparts. However, the rigid requirements and screenings have an already built-in weakness due to over-specialization." "The earned Doctor degree is supposed to be based on research work containing a theoretical utilization and the solution of a major scientific problem representing a considerable contribution to science and to practical work. It should have a serious impact". J. Chem. Educ. 1971, 48, 60; 1973, 50, 520. The pharmaceutical industry: - generic drugs account for more than half of the total market (in value) and almost 3/4 in volume (july 2011); - major generic companies: KrKa (Slovenia), Gedeon Richter (Hungary), PolPharma (Poland), Zentiva (Romania), Pharmstandard (Russia). - highest sales in cardiovascular market, followed by alimentary canal and metabolic disorders; - importantly, the health care system is run by the government, so obviously there is little impetus for significant R&D programs. http://blog.pharmexec.com/2009/09/02/pharma-industry-booming-in-eastern-europe/ http://www.espicom.com/prodcat2.nsf/Product_ID_Lookup/00000396?OpenDocument https://www.mckinseyquarterly.com/Pharmas_generics_opportunity_in_Central_and_Eastern_Europe_2186# Chemistry Nobel Prize winners - awarded from 1945-2011; chemists who were residents in their countries of birth when they received the award: Nikolay Semyonov (Russia), 1956 - for work on the mechanism of chain reactions; Jaroslav Heyrousky (Czech Republic), 1959 - for developing the polarographic method of analysis; Vladimir Prelog (Croatia), 1975 - for research into the stereochemistry of molecules and reactions; - awarded from 1945-2011; eastern european born chemists who led their research in other countries: Ilya Prigogine (born Russia), 1977 - for his work on dissipative structures, complex systems, and irreversibility; Roald Hoffmann (born Ukraine), 1981 - for the Woodward-Hoffman rule; Aaron Klug (born Lithuania), 1982 - for his development of crystallographic electron microscopy and his structural elucidation of biologically important nucleic acid-protein complexes George Olah (born Hungary), 1994 - for work on carbocations generated with superacids; Avram Hershko (born Hungary), 2004 - for the discovery of ubiquitin-mediated protein degradation. "The earned Doctor degree is not a degree in the American sense, but a sign of recongition which could be compared to our post-doctoral experience. Too many Russians remain in one place to work and study under the same man in one field. This creates inbreeding and an educational system that lacks imagination and produces research contributions not up to the level of effort exerted and manpower used" Prof. Branko Stanovnik (Ph.D, 1964) - 583 publications - heterocyclic chemistry Founding fathers: I.K.Matsurevich (active in '30-'40) - nat prod synthesis V.P.Yavorskii - chemical transformations of aliphatic compounds V.G.Shaposhnikov - aromatic and heterocyclic chemistry Czech Republic Main research centers: Prague Institute of Chemical Technology; Institute of Organic Chemistryvand Biochemistry (Prague) Active researchers: Prof. Srogl Jiri (currently at Emory Univ) - bioactive inspired metal coupling rxns (Ni and Pd catalyzed coupling of thio-esters with boronic acids) Prof. Petr Beier (currently at Univ. of Southern California) - organic sulfur, phosphorus, silicon and fluorine chemistry. Slovakia Main research centers: Slovak Academy of Sciences; Institute of Organic Chemistry; Slovak Technical Univ Main areas of research: sugars chemistry... Estonia Main research centers: Tallin Univ of Technology Active researchers: Prof. Margus Lopp - asymmetric synthesis (asymmetric Bayer Villiger ...) Latvia Main research centers: Latvian Institute of Organic Synthesis (Riga), Latvian Academy of Sciences, Riga Technical Institute Active researchers: Prof. Edgars Suna (32 publications) - asymmetric reductions Prof. E. Lukevics (1936-2009) - chemistry of organosulfur, silicon, germaniun compounds Lithuania Main research centers: Vilnius Univ Active researchers: undetectable... Romania Main research centers: Bucharest Univ Polytechnic Institute (Bucharest) Technical Univ, Cluj-Napoca Founding fathers: Prof. Costin Nenitzescu ( 1902-1970) (Friedel-Crafts reaction, first to synthesize cyclobutadiene, oxidations of aliphatics with chromiun oxidants, Nenitzescu indole synthesis) Prof. Alexandru Balaban (born 1931) (currently at UT, Austin) (theoy of aromaticity, pioneer of the chemical graph theory) Active researchers: not so much in organic chemistry... more in inorganic and analitical Bulgaria Main reseach centers: Bulgarian Academy of Sciences, Institute of Organic Chemistry Plovdiv Univ Active researchers: Prof. Vladimir Dimitrov - organometallic chemistry, sythesis of asymmetric ligands Left uncovered.... Hungary(!!), Croatia(!), Serbia(!), Macedonia, Bosnia, Moldova, Albania, Russia(!!!!) OH
Transcript of Organic Chemistry from the Eastern Bloc · PDF fileBaran Lab GM Organic Chemistry from the...
Organic Chemistry from the Eastern BlocBaran Lab GM08/13/2011 Florina Voica
Major Research Centers:Institute of Organic Chemistry, Polish Academy of SciencesUniv of WarsawAdam Mickiewiecz Univ, PoznanWarsaw Univ of TechnologyGdansk Technical Univ
Founding fathers:Osman Achmatowicz (1899-1988) - alkaloids isolation (O. Achmatowicz Jr - sugar chemistry, name rxn)Jerzy Suszko (1889-1972) - polycyclic aromatics Edwin Plazek - heterocyclic chemistryHenryk Kuczynski (1909-1991) - terpene chemistry
O
OSitBuPh2
H
TMSSO2Ph
nBuLithen MsCl
86% (over 2 steps)
TMS
PhO2S
OSitBuPh2
OMsdr 3:1
PhO2S OSitBuPh2
TMS
LDA, THF89%
TBAF41%
OHTet. Lett. 1991, 32, 531
SO2PhO
TMSnBuLi,
then HClO4, MeOH OH
OHO
(+)DET, Ti(OiPr)4, TBHP
1. TsCl, pyr2. (nC9H19)2CuLi
C9H19O
(+)-disparlureTet. Lett. 1989, 30, 2845
O
OMe
Me O
O
Me
O
Me O
HMe
OOH
1. NaOMe, 40%2. H2, Pd/SrSO3
H2, Pd/C
Me O
HMe
OOH
H
1. L-selectride2. N2H4
3. I2
Me
HMe
HOOH
H
I
N2H2
Me
HMe
HOOH
H
I
Me
HMe
THPOOH
H
OMe
1. tBuNC, NaCNBH3 Bu3SnCl, AIBN2. DHP3. MeLi, PhH
Me
HMe
THPOOH
H
O
O
1. LDA, MoOHPy2. Ph3P • • O
J. Org. Chem. 1988, 53, 4855
Prof. Jerzy Wicha
- born on February 14, 1936, Warsaw, Poland;- education: M. Sc.: Moscow State University, 1958 Ph. D.: The University of Warsaw, 1964 D. Sc.: The University of Warsaw, 1970- positions: 1958-1960 Research Associate, Institute of Pharmaceutical Industry, Warsaw1960 -1970 Instructor - reader, the University of Warsaw1970 - 1978 Docent, Institute of Organic Chemistry, Polish Academy of Sciences1978 - Professor, the same Institute- 184 publications (Scifinder) - major research topics: steroid synthesis, some guanacastepene, prostaglandins research, some methods based on the Julia olefination reaction.
Organic Chemistry from the Eastern BlocBaran Lab GM08/13/2011 Florina Voica
Me
Me
H
HTHPO
OMe
Me
H
HTHPO
HOTMSBr TMS
nBuLi, BF3•Et2O93%
Me
Me
H
HTHPO
OTMS
O
O
F3C O
Me
Me
H
HTHPO
O
O
Me
Me
H
HTHPO
O
OH
OH
Me
Me
OH
HHO
O O
Digitoxigenin
1.VO(acac)2, TBHP, 86%2. mCPBA, 87%3. TFAA, pyr, 87%
TBAF, H2O, THF, rt
J. Org. Chem. 1995, 60, 1823
Me
OMe
MeCO2Et
Me
OMe
MeEtO2C Br
Br
Br
Me
OMe
MeMe Br
Me
OMe
MeMe Br Br
Br
Me
OMe
MeMe
Me
Me
MeMe
Me
HO
LDA/THF, -78 °C then
iPr80%
1. DIBAL2. TsCl, pyr3. Superhydride 80%
CHBr3-50%NaOHCETRIMID50%, dr 1:1(separable)
MeLi/Et2O -78 °C to rtthen
MeI, -78 °C to rt60%
TsOH/aq dioxane
23-H-isocalysterol(both diastereoisomers are NPs)
J. Am. Chem. Soc. 1995, 117, 1849
Organic Chemistry from the Eastern BlocBaran Lab GM08/13/2011 Florina Voica
For more on steroid functionalization: J. Org. Chem. 2010, 75, 5388, J. Org. Chem. 1990, 55, 3484, Tetrahedron 1989, 45, 2223, Tet. Lett. 1988, 29, 4001, J. Org. Chem. 1973, 38, 1280.For some representative refs on formal syntheses of different vitamin Ds (20 papers published)-Tet. Lett. 1998, 29, 885, Synthesis 1999, 1209; J. Org. Chem. 2007, 72, 5276.For work on terpene synthesis: Tet. Lett. 2005, 46, 1149, J. Org. Chem. 2010, 75, 8337.
Prof. Mieczyslaw Makosza- born in 1934- education: M. Sc : Univ.of Leningrad, 1958 Ph.D : Technical Univ. Warsaw, 1956 D.Sc : Technical Univ. Warsaw, 1971- positions: 1975-1977, Director, Institute of Organic Chemistry and Technology, Univ. of Warsaw 1979-present, Director, Institute of Organic Chemistry, Polish Academy of Sciences.- 420 publications (Scifinder)- major research areas: phase transfer catalysis (chemistry of carbanions and carbenes), vicarious nucleophilic substitution.
Vicarious Nucleophilic Substitution of Hydrogen (VNS)- describes the reaction of a nucleophile with a electrophilic arene (nitroarenes, heteroarenes) or alkene;- the attack can occur ortho or para to the NO2 group but there are ways to achieve selectivity; disubstituted prods are usually not observed;- VNS is an "umpolung Friedel-Crafts" reaction and it complements the scope of the FC rxn since it allows functionalization of arenes which are very poor nucleophiles in SEAr.General reaction scheme:
NO2
XR
Y
basesolvent
+
NO2-
Y
R
Xbase-HX
Y
RNO2- NO2
Y
R
H+
Z = F, Cl, Br, I, OMe, OPh, SMe, Et, tBu, Ph, NMe2, CF3, CN, SO2Me, CO2H.Y (EWG) = SO2Ph, SO2NH2, CN, CO2Et, Cl, Ar etc. X (good LG) = Cl, Br, OPh, SPh etc.Typical base: KOH, NaOH, tBuOK.Typical solvent : DMSO, DMF, THF, MeOH, NH3(l).
Extensive reviews on the topic: Acc. Chem. Res. 1987, 20, 282; Synthesis 1991, 103; Chem. Soc.Rev. 2010, 39, 2855;for VNS examples on electrophilic olefins: Tetrahedron 1991, 47, 5001;for an exhaustive review on VNS on heterocycles: Chem. Rev. 2004, 104, 2631.
NO2
NC Me
Ph+ OH
Me
PhNC
tBuOKDMF/THF
-70 °CDMDO,
H2O aq. NH4Cl
83%J. Org. Chem. 1998, 63, 4390
N
N
N
N
SO2Ph
N
N
SO2Ph
SO2Ph
Cl SO2Ph
KOH, DMSO 66%
OHMeO NO2
NO2
Synthesis 1997, 1131
OHMeO NO2
NO2
CN
OMeMeO NO2
NO2
CN
OMeMeO NO2
NO2
CN
CO2Et
PhO CNtBuOK, DMF
80%
Me2SO4, NaHCO3
83%
Br
CO2Et
69%
HN
HN
O
OMeMeO H2,
PdCl2-Fe48%
HN
HN
O
OO
Damirone B
Chem. Lett. 1987, 61
NO2
NMe
SO2
Ph
NMe
SO2
N+ PhTBSO O-
NMe
SO2
PhNO
NMe
SO2
PhNTBSO
N
NMe
SO2
TBSON
NMe
SO2
DBUTBSCl
DBU-TBSOH
DBUTBSCl
hνDBU
-TBSOH
Acta Chem. Scand. 1992, 46, 689
Organic Chemistry from the Eastern BlocBaran Lab GM08/13/2011 Florina Voica
Phase transfer catalysis: A process in which a phase transfer catalyst (usually a tetraalkylammonium salt, QX++) facilitates the reaction of inorganic and organic anions or carbenes with organic electrophiles. Practically, itconsists of a two-phase mixture: the inorganic solution containing reacting anions or base thatwill generate organic anions; the organic mixture containg the organic reactants and the phasetransfer catalyst (source of lipophilic cations).General reaction scheme:- reactive inorganic anions:
Na+Y-aq + Q+X-org Na+Y-aq + Q+X-org
Q+Y-org + RX Q+X-org + RY
- in situ generated organic anions:PhCH2CNorg + Na+OH-aq PhCH-CNorgNa+int + H2Oaq
PhCH-CNorgNa+int + Q+X-org PhCH-CNorgQ+org + Na+X-aq
PhCH-CNorgQ+org + R-XorgR
Ph
CNorg+ Q+X-org
For a general review and applications see: Pure Appl. Chem. 2000, 72, 1399 and refs therein.
N+
OMe
PMBBr-
TMSCF3 (1.2 equiv)KF(s) (1.5 quiv)
Ph3SnF (0.3 equiv)DCM, rt, 24h
76% N
OMe
CF3
PMB
CAN (2.2 equiv)MeOH-H2O 4:1
90%N
OMe
CF3
J. Org. Chem. 2007, 72, 5574
Andrzej Daniewski- Institute of Organic Chemistry, Polish Academy of Sciences- Hoffman-La Roche, NJ- 89 publications (Scifinder)- major research areas: synthesis of cardiotonic steroids, vitamin D, bioactive sesquiterpenes.
Cl
OMeO
O
O
Me O
O
MeClO
MeO
O
O
MeOAcO
N2MeO B3
MeO
Me O
OH
AcOO
Me O
OAc
AcOAcO
H
MeO
+
Me
OH
HOHO
H
MeO
O
Me
OH
OH
MeO
O
H
Me
H
H
MeO
O
H
TsOAcAc2O,70%
NaOH, MeOH
BF3•Et2Oacetone, then H2O
75%
J. Org. Chem. 1975, 40, 3124, 3135
KOH, MeOH80%
1. conc HCl2. Ac2O, AcOH, 85%3. chiral resolution4. SOCl25. CH2N2, 87%
MeO
O O
O
Me
Me O
MeO
HBr, AcOH
14-dehydroequilenin
OMe
MeO
O
Me O
MeO
estrone
1. TiCl42. Zn, 85%
HClO4HBr
Tet. Lett. 1982, 23, 2411
Organic Chemistry from the Eastern BlocBaran Lab GM08/13/2011 Florina Voica
OMe
O
OMe
i-Bu2AlOH
OMe
OH
Br
Me OH
H
O
Me
HOH
Me
HO
Me
OH
Me
HO
tBuCu, DIBALHMPA
57%
1. PDC, 65%2. Wittig, 92%3. LAH, 87%
J. Org. Chem. 1988, 53, 5534
Br2
Me O
O
Me O
OHOH
OTBS
TBSOO H
Me O
HHO
OAc
H
H
OAc
OMe
O
H
H
OAc
OAc
H
H
OAc
Me OAcHO
H
H
OAc
Me OH
H
HMe
OH
OH
tBuCu, DIBAL70%
7 steps
1. mCPBA2. Martin rgnt 90%
1. LAH2. Ac2O3. Martin rgnt90% (3 steps)
1. N2H4, H2O22. SeO2
60%
1. Martin rgnt2. KOH
OEt
Me
O
compactin
Tet. Lett. 1990, 31, 5599
Prof. Janusz Jurczak- Ph.D, Institute of Organic Chemistry, Univ of Warsaw, 1970- Post-doc, V. Prelog, ETH Zurich, 1971-1972- Habilitation, Institute of Organic Chemistry, Univ of Warsaw, 1979- Professor, Dept of Chemistry, Univ of Warsaw, 1991- 457 publications (Scifinder)- major research areas: sugar chemistry, high-pressure rxns (Polish specialty), supramolecular chemistry (criptands).
The case for high pressure DA reaction:- negative volume of activation (i.e. the volume occupied by the transition state is smaller than that of the reactants)- high pressure effects on the DA rxn: i) acceleration of the rxn ii) modification of regio- and diastereoselectivity iii) changes in chemical equilibria- equation describing rate dependency: δ ln k / δP = - δV / RT (k - rxn rate, P - pressure, V - transitions state volume, T - temp)- high pressure ~ 12-25 kbar- commonly used technique in industry and academic labs- cases when high pressure does the job: hindered dienes/dienophiles, LA/temp sensitive substrates, whenever you might want different product distribution.
Synthesis 1979, 41; Chem. Commun. 1983, 540; Synthesis 1985, 928.
OMe
C5H11
O+
O
OMe
C5H11
O
O
C5H11
15-20kbar50-65 °C,
Et2O28%
1. MoO3, 30%H2O22. Ac2O, pyr3. 10% Pd/C
24% overall
J. Org. Chem. 1981, 46, 2230
OMe
+H
OMe
NBocBzl
OMe
OMe
NBocBzlH
OMe
OMe
NBocBzlH
1. 15 kbar, 2% Eu(fod)350 °C, Et2O
2. PPTS, rt, MeOH80%, dr 16:1
major
+
J. Org. Chem. 1989, 54, 3759 purpurosamine B
Organic Chemistry from the Eastern BlocBaran Lab GM08/13/2011 Florina Voica
Prof. Marek Chmielewski- Institute of Organic Chemistry, Polish Academy of Sciences, Warsaw- 298 publications (Scifinder)- major research areas: sugar chemistry, β-lactam containing natural products,high pressure reactions, asymmetric reactions.
O
TMSO
N• O
+
1 equiv3 equiv
1. CDCl3, rt, 1 atm, 6h, 42%2. steps
OTMSCCl3O
O
HOOH
NBn
NO Bn
O OHHO
J. Org. Chem. 1986, 51, 2395Tet. Lett. 1987, 28, 3035
N+-O
BnO
F
OO
+N
O
OO
OBn
F
CuI (0.1 equiv), TMG (2 equiv),
ACN, 44%
NO
O
OBn
F
NO
OBn
F
OH
F
J. Org. Chem. 2011 ASAPEzetimibe
O
Prof. Bogdan Marciniec- born 1941- Ph. D, 1970, Adam Mickiewicz Univ, Poznan- Postdoc, 1971-1972, Kansas Univ - Habilitation, 1975, Adam Mickiewicz Univ, Poznan- Professor, 1986, Adam Mickiewicz Univ, Poznan- 298 publications (Scifinder)- major research areas: organosilicon chemistry , catalysis, macromolecular organosilicon structures.
General reaction mechanism for the sylilative coupling of olefins with vinyl silanes:
SiR3
M
H HSiR3
H H
M SiR3
M H
R1
M
R1 HSiR3
H HM
H HR1
H SiR3+
SiR3
R1
RSiR3
M = Ru, Rh, CoR = alkyl, aryl, alkoxyR1 = alkyl, pheyl, OR, SiR3, -pyrrolidinone, carbazole
Acc. Chem. Res. 2007, 40, 943
O
O
Si
Si
RuHClCO(PPh3)3 (1 mol%)80 °C, 1h
85%SiO O
SiSi
OSi Si
OSi
TMSO
+Si(OEt)3
TMSO
Si(OEt)3
92%
H2O/HCl88%
RuHCl(CO)(PCy3) (1 mol%)PhMe, 110 °C
J. Org. Chem. 2005, 70, 370
Angew. Chem. Int. Ed. 2006, 45, 8180
Organic Chemistry from the Eastern BlocBaran Lab GM08/13/2011 Florina Voica
Other accomplished polish chemists:-Prof. Tadeusz Jagodzinki - Technical Univ. of Szczecin - main research areas: synthesis and reactivity of thioamide derivatives of benzene and 5-membered heterocyles (Chem. Rev. 2003, 103, 197) - Prof. Maria Rozwadowska - Adam Michiewicz Univ, Poznan - main research areas: synthesis of isoquinoline alkaloids, chiral amines and sulfoxides. (Chem. Rev. 2004, 104, 3341)- Prof. Karol Grela - Institute of Organic Chemistry, Polish Academy of Sciences - main research areas: olefin metathesis.
Main research centers:Univ of Ljublijana (first chem PhD 1920)National Institute of Chemistry, LjubljianaFounding fathers:Fritz Pregl (1869-1930) - quantitative organic microanalysisMiha Tisler (1926-2001) - hetrocyclic chemistry
Prof. Marko Zupan- born- Ph. D. 1974, Faculty of Chemistry and Chemical Technology, University of Ljubljana- Associate Professor, 1982-1987, University of Ljubljana- Professor, 1987-, University of Ljubljana- 233 publications (Scifinder)- main research areas: chemistry of halosubstituted organic molecules, fluorination of organic molecules ( Sarlah says... " [M. Zupan] was the first guy who started using XeF2 in organic synthesis")
Electrophilic fluorination with XeF2, CeSO4F
F3C Br
1. Mg, Et2O2. CS23. XeF2
F3C CF377%
Tet. Lett. 1990, 31, 3357
FF
F
XeF2105 °C, 2.5h
28% 42% 30%
+ +
Bull. Chem. Soc. Jpn. 1986, 59, 1659
XeF2 not an ideal fluorinating reagent...- no regioselectivity for aromatic substrates- olefin/aromatic ring substitution very important for reactivity...- strong oxidant, minimal FG tolerance- it usually requires an acid catalyst for activation- product distribution very sensitive to rxnconditions
Ph
MeO
CsSO4F (1.1 equiv), ACNrt, 1.5 h
84% Ph F
MeJ. Org. Chem. 1992, 57, 5334
N N NF OSO2F+
CsSO4F (2 equiv), rtcyclohexane
70% 30%
Tet. Lett. 1990, 31, 775
N
NMe
Me
O
OCsSO4F (1.3 equiv)
MeOH, 40 ° CF N
NMe
Me
O
O
FF
OMe72%Tetrahedron 1990, 46, 3093
Electrophilic fluorination with N-F reagents (Selectfluor, Accufluor)
N+
N+
Cl
F
Selectfluor
N+
N+F
(BF4-)2
Accufluor
O O
MeSelectfluorsolvent free
87%
O O
MeF
Me O
HO
Me O
O
FSelectfluor (1.05 equiv)H2O, 60 °C
74%
OEt OEtF
Selectfluorsolvent free
61%
Tet. Lett. 2007, 48, 2671
Org. Lett. 2004, 6, 4973
Accufluor (1.1 equiv)ACN, 70 °C
NHAc
F F
NHAc
+
1 : 374%
Chem. Commun. 1996, 2247
(BF4-)2
Organic Chemistry from the Eastern BlocBaran Lab GM08/13/2011 Florina Voica
Main research centers: National Academy of Sciences, KievKiev Polytechnic InstituteKarkow National Univ
Prof. Andrey A Fokin- Dept. of Organic Chemistry, Kiev Polytechnic Institute- 104 publications (Scifinder)- major research areas: nanodiamonds, cage structures, alkane functionalization, computational chemistry of radicals and radical cations.
Br50% NaOH/CBr4DCM, Et3BnNCl, 40 °C
37%
50% NaOH/CBr4DCM, Et3BnNCl, 40 °C
44%
INaOH, CHI3,
rt, 24h92%
nPr
Et EtI
I
NaOH, CHI3, rt, 24h92%
Br +
4 : 1
Angew. Chem. Int. Ed. 1998, 37, 1895; 1999, 38, 2786O O
SO
NaH. DMSO130 °C, 12h
96%
p-TSA, DCM
96%
Org. Lett. 2007, 9, 2541
O MeHOO
H2SO480 °C65%
MeMgBr93%
CF3CO3HTFA80%
Org. Lett. 2009, 11, 3068
Main research centers:National Academy of Sciences of BelarusBelorussian State Univ
Founding fathers: too close to Russia, difficult to define..
Prof. Oleg Kulinkovich- born 1948 in Estonia- Ph. D, 1975, Belorussian State Univ, Minsk (prof. Tishchenko)- Professor, 1987, Belorussian State Univ, Minsk- 174 publications (Scifinder)- major research areas: development of cat and noncatalytic methods basedon transformations of strained organic and organometallic compounds
Kulinkovich reaction:
RCO2Me
ROH
1. EtMgBr (2 equiv)Ti(OiPr)4 (5-10 mol%)
Et2O, rt, 1h2. 5% aq H2SO4, 5 °C
76-95%
Synthesis, 1989, 234Chem. Rev. 2003, 103, 2597
OH8
OH8HO
C17H35
OH
MeC17H35
8
MeC17H35
7
MeC17H35
7
MeMe
O
1. ethyl stearate (1 equiv)Ti(OiPr)4 (1 equiv)
C6H10MgBr (6 quiv)2. H+, H2O N2H4, KOH, 190 °C
56%
1. P, I2150 °C2. KOtBu, DMSO
1. MeCO2Et (1.4 equiv)Ti(OiPr)4 (1.4 equiv)
C6H10MgBr (7.1 equiv)2. H+, H2O, 64%
3, 11 - dimethylnonacosan-2-one
3. KOH, THF, 67%
Tet. Lett. 1998, 39, 1823
Me
OH
Me
OH
2
1. Ti(OiPr)5 (0.5 equiv)iPrMgBr (2 equiv),
Et2O, rt2. H+, H2O
72%
Synlett 2003, 967For more on red coupling, see Ian Young GM
C5H12
Organic Chemistry from the Eastern BlocBaran Lab GM08/13/2011 Florina Voica
σH complex
vit D3 metabolite
Organic Chemistry from the Eastern BlocBaran Lab GM08/13/2011 Florina Voica
The goal of this presentation is to offer a detailed perspective on the state of art in organic chemistry research in the major academic centers in former Eastern Bloc countries (Poland, Czech Republic, Slovakia, Hungary, Slovenia, Croatia, Serbia, Macedonia, Albania, Bulgaria, Romania, Moldova, Ukraine, Belarus, Lithuania, Latvia, Estonia). The analysis for each individual country consists in identifying the researchers who have madesignificant contributions to the field.
Historic context:- The Eastern Bloc refers to the region in Europe which entered under Soviet influence after WWII (Yalta conferene, 1945);- These were communist countries, either directly reporting to Moscow, or having more "independent" communist regimes;- Under the strict, totalitarian policies, the economic development was "extensive rather than intensive", with chracteristic shortages of goods and minimal innovation; - After the fall of USSR (1989-1991), these countries adopted the free market economic model (and democratic governments), but in most cases the '90s remain a period of slow development (transition period/lost generation);- Nov 1993, The Maastricht Treaty established The European Union; - WIth the exception of Albania, Serbia, Montenegro, Croatia and Russia, all former communist countries are now part of the EU;
General aspects:
The scientist in society:During the almost half a century of soviet cultural influence, science and technology served an important part of national politics and identity. However, significant efforts were focused on pure science and theoretical research, with little practical applications or economic impact.
The educational system"In spite of all the apparent shortcomings and faults, the Russian secondary schools seem to prepare the students relatively well for life and for higher education, especially in the sciences and mathematics. The intensity of the work and the student's motivation to succeed is a big factor. Admission to higher education is a crucial, life-long decision and it is made while the student in still in the secondary school."
"In general, the Soviet Educators in higher educational institutions receive and work with a better motivated and selected student than their American counterparts. However, the rigid requirements and screenings have an already built-in weakness due to over-specialization."
"The earned Doctor degree is supposed to be based on research work containing a theoretical utilization and the solution of a major scientific problem representing a considerable contribution to science and to practical work. It should have a serious impact".
J. Chem. Educ. 1971, 48, 60; 1973, 50, 520.
The pharmaceutical industry: - generic drugs account for more than half of the total market (in value) and almost 3/4 in volume (july 2011);- major generic companies: KrKa (Slovenia), Gedeon Richter (Hungary), PolPharma (Poland), Zentiva (Romania), Pharmstandard (Russia).- highest sales in cardiovascular market, followed by alimentary canal and metabolic disorders; - importantly, the health care system is run by the government, so obviously there is little impetus for significant R&D programs.
http://blog.pharmexec.com/2009/09/02/pharma-industry-booming-in-eastern-europe/http://www.espicom.com/prodcat2.nsf/Product_ID_Lookup/00000396?OpenDocument
https://www.mckinseyquarterly.com/Pharmas_generics_opportunity_in_Central_and_Eastern_Europe_2186#
Chemistry Nobel Prize winners - awarded from 1945-2011; chemists who were residents in their countries of birth when they received the award: Nikolay Semyonov (Russia), 1956 - for work on the mechanism of chain reactions; Jaroslav Heyrousky (Czech Republic), 1959 - for developing the polarographic method of analysis; Vladimir Prelog (Croatia), 1975 - for research into the stereochemistry of molecules and reactions;- awarded from 1945-2011; eastern european born chemists who led their research in other countries: Ilya Prigogine (born Russia), 1977 - for his work on dissipative structures, complex systems, and irreversibility; Roald Hoffmann (born Ukraine), 1981 - for the Woodward-Hoffman rule; Aaron Klug (born Lithuania), 1982 - for his development of crystallographic electron microscopy and his structural elucidation of biologically important nucleic acid-protein complexes George Olah (born Hungary), 1994 - for work on carbocations generated with superacids; Avram Hershko (born Hungary), 2004 - for the discovery of ubiquitin-mediated protein degradation.
"The earned Doctor degree is not a degree in the American sense, but a sign of recongition which could be compared to our post-doctoral experience. Too many Russians remain in one place to work and study under the same man in one field. This creates inbreeding and an educational system that lacks imagination and produces research contributions not up to the level of effort exerted and manpower used"
Prof. Branko Stanovnik (Ph.D, 1964)- 583 publications - heterocyclic chemistry
Founding fathers:I.K.Matsurevich (active in '30-'40) - nat prod synthesisV.P.Yavorskii - chemical transformations of aliphatic compoundsV.G.Shaposhnikov - aromatic and heterocyclic chemistry
Czech Republic
Main research centers: Prague Institute of Chemical Technology;Institute of Organic Chemistryvand Biochemistry (Prague)
Active researchers: Prof. Srogl Jiri (currently at Emory Univ) - bioactive inspired metal coupling rxns (Ni and Pd catalyzed coupling of thio-esters with boronic acids)Prof. Petr Beier (currently at Univ. of Southern California) - organic sulfur, phosphorus, silicon andfluorine chemistry.
Slovakia
Main research centers: Slovak Academy of Sciences;Institute of Organic Chemistry; Slovak Technical Univ
Main areas of research: sugars chemistry...
Estonia
Main research centers: Tallin Univ of Technology
Active researchers: Prof. Margus Lopp - asymmetric synthesis (asymmetric Bayer Villiger ...)
Latvia
Main research centers: Latvian Institute of Organic Synthesis (Riga), Latvian Academy of Sciences,Riga Technical Institute
Active researchers: Prof. Edgars Suna (32 publications) - asymmetric reductionsProf. E. Lukevics (1936-2009) - chemistry of organosulfur, silicon, germaniun compounds
Lithuania
Main research centers: Vilnius UnivActive researchers: undetectable...
Romania
Main research centers: Bucharest UnivPolytechnic Institute (Bucharest)Technical Univ, Cluj-Napoca
Founding fathers:Prof. Costin Nenitzescu ( 1902-1970) (Friedel-Crafts reaction, first to synthesizecyclobutadiene, oxidations of aliphatics with chromiun oxidants, Nenitzescu indole synthesis)Prof. Alexandru Balaban (born 1931) (currently at UT, Austin) (theoy of aromaticity, pioneer of the chemical graph theory)
Active researchers: not so much in organic chemistry... more in inorganic and analitical
Bulgaria
Main reseach centers: Bulgarian Academy of Sciences, Institute of Organic ChemistryPlovdiv Univ
Active researchers: Prof. Vladimir Dimitrov - organometallic chemistry, sythesis of asymmetric ligands
Left uncovered....Hungary(!!), Croatia(!), Serbia(!), Macedonia, Bosnia, Moldova, Albania, Russia(!!!!)
OH
