Baran Lab GM 08/13/2011 Organic Chemistry from the Eastern Bloc 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". "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"

Chemistry Nobel Prize winners J. Chem. Educ. 1971, 48, 60; 1973, 50, 520. - 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 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; http://blog.pharmexec.com/2009/09/02/pharma-industry-booming-in-eastern-europe/ - importantly, the health care system is run by the government, so obviously there is little impetus for significant R&D programs. http://www.espicom.com/prodcat2.nsf/Product_ID_Lookup/00000396?OpenDocument https://www.mckinseyquarterly.com/Pharmas_generics_opportunity_in_Central_and_Eastern_Europe_2186#

Baran Lab GM 08/13/2011 Organic Chemistry from the Eastern Bloc Florina Voica Major Research Centers: O Institute of Organic Chemistry, Polish Academy of Sciences nBuLi, TMS Univ of Warsaw SO2Ph OH Adam Mickiewiecz Univ, Poznan then HClO4, MeOH Warsaw Univ of Technology Gdansk Technical Univ (+)DET, Ti(OiPr)4, TBHP Founding fathers: 1. TsCl, pyr Osman Achmatowicz (1899-1988) - alkaloids isolation 2. (nC9H19)2CuLi (O. Achmatowicz Jr - sugar chemistry, name rxn) Jerzy Suszko (1889-1972) - polycyclic aromatics C9H19 OH Edwin Plazek - heterocyclic chemistry O O Henryk Kuczynski (1909-1991) - terpene chemistry (+)-disparlure Tet. Lett. 1989, 30, 2845 Prof. Jerzy Wicha O O Me Me - born on February 14, 1936, Warsaw, Poland; O - education: Me Me 1. NaOMe, 40% Me H M. Sc.: Moscow State University, 1958 2. H2, Pd/SrSO3 Ph. D.: The University of Warsaw, 1964 OH D. Sc.: The University of Warsaw, 1970 O - positions: O O O 1958-1960 Research Associate, Institute of Pharmaceutical Industry, Warsaw 1960 -1970 Instructor - reader, the University of Warsaw H2, Pd/C 1970 - 1978 Docent, Institute of Organic Chemistry, Polish Academy of Sciences I I Me O 1978 - Professor, the same Institute Me Me - 184 publications (Scifinder) 1. L-selectride Me H - major research topics: steroid synthesis, some guanacastepene, Me H Me H 2. N2H4 prostaglandins research, some methods based on the Julia olefination N2H2 3. I2 reaction. OH OH OH HO HO O H H H SO2Ph TMS OSitBuPh TMS 2 1. tBuNC, NaCNBH nBuLi OSitBuPh2 3 Bu SnCl, AIBN O then MsCl dr 3:1 3 H 2. DHP PhO2S OMs O 86% (over 2 steps) 3. MeLi, PhH O LDA, THF Me 89% O Me Me 1. LDA, MoOHPy Me H 2. Ph3P • • O Me H TBAF TMS 41% PhO S OH OH 2 OSitBuPh2 OH THPO THPO Tet. Lett. 1991, 32, 531 H J. Org. Chem. 1988, 53, 4855 H

Baran Lab GM 08/13/2011 Organic Chemistry from the Eastern Bloc Florina Voica

EtO2C Br O CO2Et Me Me HO Me LDA/THF, -78 °C then Me Br Br TMS TMS Me nBuLi, BF •Et O Me Me Me 3 2 Br iPr H 93% H 80% THPO THPO H H OMe OMe

1.VO(acac)2, TBHP, 86% 1. DIBAL 2. mCPBA, 87% 2. TsCl, pyr 3. TFAA, pyr, 87% 3. Superhydride 80%

F3C O O O Br Br O Me Me Me Br Me Br TMS Me Me TBAF, H O, CHBr -50%NaOH 2 Me 3 Me THF, rt CETRIMID O O Me 50%, dr 1:1 Me H H (separable) THPO THPO H H

OMe OMe

MeLi/Et2O -78 °C to rt then MeI, -78 °C to rt 60% O O O Me Me Me OH Me Me Me Me Me Me Me Me TsOH/aq dioxane Me H OH OH THPO HO H H HO Digitoxigenin OMe 23-H-isocalysterol J. Org. Chem. 1995, 60, 1823 (both diastereoisomers are NPs) J. Am. Chem. Soc. 1995, 117, 1849

Baran Lab GM 08/13/2011 Organic Chemistry from the Eastern Bloc Florina Voica

For more on steroid functionalization: J. Org. Chem. 2010, 75, 5388, J. Org. Chem. 1990, 55, 3484, NO2 tBuOK DMF/THF DMDO, Ph Tetrahedron 1989, 45, 2223, Tet. Lett. 1988, 29, 4001, J. Org. Chem. 1973, 38, 1280. Ph aq. NH4Cl -70 °C H2O For some representative refs on formal syntheses of different vitamin Ds (20 papers published)- + NC OH Tet. Lett. 1998, 29, 885, Synthesis 1999, 1209; J. Org. Chem. 2007, 72, 5276. NC Me Me For work on terpene synthesis: Tet. Lett. 2005, 46, 1149, J. Org. Chem. 2010, 75, 8337. 83%

SO2Ph SO2Ph Prof. Mieczyslaw Makosza J. Org. Chem. 1998, 63, 4390 - born in 1934 N N N - education: Cl SO2Ph M. Sc : Univ.of Leningrad, 1958 66% Ph.D : Technical Univ. Warsaw, 1956 KOH, DMSO N D.Sc : Technical Univ. Warsaw, 1971 N N - positions: Chem. Lett. 1987, 61 1975-1977, Director, Institute of Organic Chemistry and Technology, SO2Ph Univ. of Warsaw TBSO O- NO + 1979-present, Director, Institute of Organic Chemistry, Polish Academy of 2 N Ph NO Ph Sciences. Ph DBU DBU - 420 publications (Scifinder) TBSCl -TBSOH - major research areas: phase transfer catalysis (chemistry of carbanions SO2 SO2 and carbenes), vicarious nucleophilic substitution. SO2 N N N Me Me Me Vicarious Nucleophilic Substitution of Hydrogen (VNS) - describes the reaction of a nucleophile with a electrophilic arene (nitroarenes, heteroarenes) or DBU alkene; TBSCl - the attack can occur ortho or para to the NO2 group but there are ways to achieve selectivity; DBU TBSO TBSO disubstituted prods are usually not observed; N N N - VNS is an "umpolung Friedel-Crafts" reaction and it complements the scope of the FC rxn since -TBSOH hν Ph it allows functionalization of arenes which are very poor nucleophiles in SEAr. General reaction scheme: SO2 SO2 SO2 N N N base Me Me Me base + R X solvent -HX H Acta Chem. Scand. 1992, 46, 689 + X OMe Y Y Y OH OH Y Me2SO4, MeO NO MeO NO MeO NO2 2 PhO CN 2 NaHCO3 NO NO - R NO - R NO R 2 2 2 2 83% tBuOK, DMF CN CN σH complex 80%

Z = F, Cl, Br, I, OMe, OPh, SMe, Et, tBu, Ph, NMe2, CF3, CN, SO2Me, CO2H. NO2 NO2 NO2 Y (EWG) = SO Ph, SO NH , CN, CO Et, Cl, Ar etc. 2 2 2 2 O OMe OMe CO Et X (good LG) = Cl, Br, OPh, SPh etc. H 2 O H H , Typical base: KOH, NaOH, tBuOK. N MeO N 2 MeO NO2 PdCl2-Fe Typical solvent : DMSO, DMF, THF, MeOH, NH3(l). Br 48% CN 69% Extensive reviews on the topic: Acc. Chem. Res. 1987, 20, 282; Synthesis 1991, 103; Chem. Soc. Rev. 2010, 39, 2855; HN HN NO2 for VNS examples on electrophilic olefins: Tetrahedron 1991, 47, 5001; CO2Et for an exhaustive review on VNS on heterocycles: Chem. Rev. 2004, 104, 2631. Damirone B O O Synthesis 1997, 1131

Baran Lab GM 08/13/2011 Organic Chemistry from the Eastern Bloc Florina Voica

Phase transfer catalysis: Me O A process in which a phase transfer catalyst (usually a tetraalkylammonium salt, QX++) facilitates the O OAc AcO reaction of inorganic and organic anions or carbenes with organic electrophiles. Practically, it Me O O consists of a two-phase mixture: the inorganic solution containing reacting anions or base that N MeO 3B will generate organic anions; the organic mixture containg the organic reactants and the phase 2 transfer catalyst (source of lipophilic cations). OH O General reaction scheme: MeO - reactive inorganic anions: TsOAc + - + - + - + - Na Y aq + Q X org Na Y aq + Q X org Ac2O, 70% O Me O Me + - + - AcO Q Y org + RX Q X org + RY HO AcO H HO H NaOH, MeOH - in situ generated organic anions: + - - + OH OAc PhCH2CNorg + Na OH aq PhCH CNorgNa int + H2Oaq MeO MeO PhCH-CN Na+ + Q+X- PhCH-CN Q+ + Na+X- org int org org org aq BF3•Et2O Ph acetone, then H2O 75% - + + - PhCH CNorgQ org + R-Xorg + Q X org R CNorg Me O Me O O For a general review and applications see: Pure Appl. Chem. 2000, 72, 1399 and refs therein. H H OMe TMSCF3 (1.2 equiv) OMe OMe KF (1.5 quiv) (s) CAN (2.2 equiv) H OH H H Ph3SnF (0.3 equiv) MeOH-H2O 4:1 MeO MeO DCM, rt, 24h 90% J. Org. Chem. 1975, 40, 3124, 3135 N+ N CF3 N CF3 Br- 76% O PMB PMB J. Org. Chem. 2007, 72, 5574 Me O O Me Andrzej Daniewski HBr, AcOH - Institute of Organic Chemistry, Polish Academy of Sciences MeO - Hoffman-La Roche, NJ - 89 publications (Scifinder) - major research areas: synthesis of cardiotonic steroids, vitamin D, bioactive sesquiterpenes. O MeO 1. conc HCl 1. TiCl4 14-dehydroequilenin 2. Ac2O, AcOH, 85% 2. Zn, 85% O O Cl 3. chiral resolution O Me O Cl Me O Me KOH, MeOH Me 4. SOCl2 80% + 5. CH2N2, 87% MeO O HClO4 O OMe HBr O estrone O MeO MeO Tet. Lett. 1982, 23, 2411

Baran Lab GM 08/13/2011 Organic Chemistry from the Eastern Bloc Florina Voica

Me O Me O Me O Prof. Janusz Jurczak tBuCu, DIBAL - Ph.D, Institute of Organic Chemistry, Univ of Warsaw, 1970 HMPA Br2 - Post-doc, V. Prelog, ETH Zurich, 1971-1972 57% - Habilitation, Institute of Organic Chemistry, Univ of Warsaw, 1979 O i-Bu AlO O - Professor, Dept of Chemistry, Univ of Warsaw, 1991 2 H H - 457 publications (Scifinder) Br - major research areas: sugar chemistry, high-pressure rxns (Polish specialty), supramolecular chemistry (criptands). Me HO Me OH Me 1. PDC, 65% OH 2. Wittig, 92% Me Me 3. LAH, 87% The case for high pressure DA reaction: O - negative volume of activation (i.e. the volume occupied by the transition state is smaller than that H O H of the reactants) OH H - high pressure effects on the DA rxn: vit D3 metabolite J. Org. Chem. 1988, 53, 5534 i) acceleration of the rxn ii) modification of regio- and diastereoselectivity OTBS iii) changes in chemical equilibria OH OAc - equation describing rate dependency: O δ ln k / δP = - δV / RT (k - rxn rate, P - pressure, V - transitions state volume, T - temp) TBSO H H - high pressure ~ 12-25 kbar O O - commonly used technique in industry and academic labs tBuCu, DIBAL 7 steps HO H - cases when high pressure does the job: hindered dienes/dienophiles, LA/temp sensitive 70% substrates, whenever you might want different product distribution. Me Me O Me O O Synthesis 1979, 41; Chem. Commun. 1983, 540; Synthesis 1985, 928. 1. mCPBA 2. Martin rgnt 15-20kbar 90% 1. MoO3, 30%H2O2 50-65 °C, C H C5H11 2. Ac2O, pyr C5H11 5 11 Et O + 2 3. 10% Pd/C OAc O OAc 1. LAH OAc O 28% 24% overall O 1. N H , H O 2 4 2 2 H 2. Ac O H H 2. SeO 2 OMe 2 3. Martin rgnt OMe O H 60% H 90% (3 steps) H J. Org. Chem. 1981, 46, 2230 OAc O O HO Me OAc Me 1. Martin rgnt Et NBocBzl 1. 15 kbar, 2% Eu(fod)3 NBocBzl NBocBzl 2. KOH H H 50 °C, Et2O O H 2. PPTS, rt, MeOH Me OH + Me Me Me 80%, dr 16:1 + OAc O O O Tet. Lett. 1990, OMe major H H 31, 5599 OMe OMe O O H H H J. Org. Chem. 1989, 54, 3759 compactin purpurosamine B Me OH Me

Baran Lab GM 08/13/2011 Organic Chemistry from the Eastern Bloc Florina Voica

Prof. Marek Chmielewski Prof. Bogdan Marciniec - Institute of Organic Chemistry, Polish Academy of Sciences, Warsaw - born 1941 - 298 publications (Scifinder) - Ph. D, 1970, Adam Mickiewicz Univ, Poznan - major research areas: sugar chemistry, β-lactam containing natural products, - Postdoc, 1971-1972, Kansas Univ high pressure reactions, asymmetric reactions. - 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:

R1 M H SiR O 1. CDCl , rt, SiR3 3 O • 3 O NBn O OH SiR R N 1 atm, 6h, 42% HO 3 + 2. steps O CCl O N H H TMSO 3 H H HO O Bn H SiR3 M OTMS 3 equiv OH M + M SiR3 1 equiv SiR R1 3 H H J. Org. Chem. 1986, 51, 2395 R H Tet. Lett. 1987, 28, 3035 H H 1

OBn M SiR BnO R1 3 CuI (0.1 equiv), O O O TMG (2 equiv), M = Ru, Rh, Co ACN, 44% + R = alkyl, aryl, alkoxy Acc. Chem. Res. 2007, 40, 943 O R = alkyl, pheyl, OR, SiR , -pyrrolidinone, carbazole N+ N 1 3 -O O F Si O RuHClCO(PPh3)3 (1 mol%) Si Si F H O/HCl 80 °C, 1h Si Si 2 O O 85% 88% O O Si Si O Si OBn OBn OH J. Org. Chem. 2005, 70, 370

F O Si(OEt)3

N TMSO TMSO N O RuHCl(CO)(PCy3) (1 mol%) Si(OEt)3 O + PhMe, 110 °C 92% Ezetimibe F F J. Org. Chem. 2011 ASAP Angew. Chem. Int. Ed. 2006, 45, 8180

Baran Lab GM Organic Chemistry from the Eastern Bloc 08/13/2011 Florina Voica

Other accomplished polish chemists: Me Me -Prof. Tadeusz Jagodzinki - Technical Univ. of Szczecin CsSO4F (1.1 equiv), ACN - main research areas: synthesis and reactivity of thioamide derivatives O rt, 1.5 h J. Org. Chem. 1992, 57, 5334 of benzene and 5-membered heterocyles (Chem. Rev. 2003, 103, 197) Ph 84% Ph F - 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 CsSO F (2 equiv), rt - main research areas: olefin metathesis. N 4 N F N OSO2F cyclohexane + Main research centers: Tet. Lett. 1990, 31, 775 Univ of Ljublijana (first chem PhD 1920) National Institute of Chemistry, Ljubljiana 70% 30% Founding fathers: O O Fritz Pregl (1869-1930) - quantitative organic microanalysis F Miha Tisler (1926-2001) - hetrocyclic chemistry Me F CsSO4F (1.3 equiv) Me F N MeOH, 40 ° C N Tetrahedron 1990, 46, 3093 Prof. Branko Stanovnik (Ph.D, 1964) - 583 publications - heterocyclic chemistry 72% O N O N OMe Prof. Marko Zupan Me Me - born - Ph. D. 1974, Faculty of Chemistry and Chemical Technology, Electrophilic fluorination with N-F reagents (Selectfluor, Accufluor) University of Ljubljana - Associate Professor, 1982-1987, University of Ljubljana F F O O O O - Professor, 1987-, University of Ljubljana + Selectfluor N N+ solvent free - 233 publications (Scifinder) Me Me - main research areas: chemistry of halosubstituted organic molecules, (BF -) - 4 2 (BF4 )2 F fluorination of organic molecules ( Sarlah says... " [M. Zupan] was the 87% N+ + first guy who started using XeF2 in organic synthesis") N OH F Cl OEt Selectfluor OEt Selectfluor Accufluor solvent free 61% Electrophilic fluorination with XeF2, CeSO4F XeF2 not an ideal fluorinating reagent... - no regioselectivity for aromatic substrates Tet. Lett. 2007, 48, 2671 1. Mg, Et2O - olefin/aromatic ring substitution very O O 2. CS2 Me Me 3. XeF important for reactivity... 2 - strong oxidant, minimal FG tolerance 77% - it usually requires an acid catalyst for Selectfluor (1.05 equiv) F F3C Br F3C CF3 activation H2O, 60 °C - product distribution very sensitive to rxn 74% Tet. Lett. 1990, 31, 3357 Org. Lett. 2004, 6, 4973 conditions HO O XeF 2 F NHAc 105 °C, 2.5h NHAc F + + Accufluor (1.1 equiv) ACN, 70 °C + 28% 42% F 30% 74% F F Bull. Chem. Soc. Jpn. 1986, 59, 1659 Chem. Commun. 1996, 2247 1 : 3

Baran Lab GM 08/13/2011 Organic Chemistry from the Eastern Bloc Florina Voica Main research centers: Main research centers: National Academy of Sciences, Kiev National Academy of Sciences of Belarus Kiev Polytechnic Institute Belorussian State Univ Karkow National Univ Founding fathers: Founding fathers: too close to Russia, difficult to define.. 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

Prof. Andrey A Fokin Prof. Oleg Kulinkovich - Dept. of Organic Chemistry, Kiev Polytechnic Institute - born 1948 in Estonia - 104 publications (Scifinder) - Ph. D, 1975, Belorussian State Univ, Minsk (prof. Tishchenko) - major research areas: nanodiamonds, cage structures, alkane - Professor, 1987, Belorussian State Univ, Minsk functionalization, computational chemistry of radicals and radical cations. - 174 publications (Scifinder) - major research areas: development of cat and noncatalytic methods based on transformations of strained organic and organometallic compounds

I Kulinkovich reaction: 50% NaOH/CBr NaOH, CHI3, 4 Br rt, 24h 1. EtMgBr (2 equiv) DCM, Et3BnNCl, 40 °C Ti(OiPr)4 (5-10 mol%) 37% 92% OH Et2O, rt, 1h R Synthesis, 1989, 234 2. 5% aq H SO , 5 °C CO Me 2 4 Chem. Rev. 2003, 103, 2597 NaOH, CHI , 2 3 I Et Et R 76-95% 50% NaOH/CBr4 rt, 24h Br + DCM, Et3BnNCl, 40 °C C5H12 92% nPr I 44% 4 : 1 1. ethyl stearate (1 equiv) Ti(OiPr)4 (1 equiv) Angew. Chem. Int. Ed. 1998, 37, 1895; 1999, 38, 2786 C H MgBr (6 quiv) 6 10 C17H35 2. H+, H O 8 OH N2H4, KOH, 190 °C O O 2 OH HO O 8 56% S 1. MeCO2Et (1.4 equiv) 1. P, I2 p-TSA, DCM Ti(OiPr)4 (1.4 equiv) 150 °C Me 2. KOtBu, Me NaH. DMSO 96% C6H10MgBr (7.1 equiv) + DMSO 130 °C, 12h 2. H , H2O, 64% C17H35 C17H35 96% 8 OH Org. Lett. 2007, 9, 2541 3. KOH, THF, 67% 7

HO 1. Ti(OiPr)5 (0.5 equiv) O Me Me Me O iPrMgBr (2 equiv), Et O, rt H2SO4 CF CO H C H Me OH 2 OH 3 3 17 35 2. H+, H O 80 °C MeMgBr TFA 7 2 65% 93% 80% O Me 72% Me 3, 11 - dimethylnonacosan-2-one 2 Synlett 2003, 967 Org. Lett. 2009, 11, 3068 Tet. Lett. 1998, 39, 1823 For more on red coupling, see Ian Young GM

Baran Lab GM 08/13/2011 Organic Chemistry from the Eastern Bloc Florina Voica

Czech Republic Founding fathers: Prof. Costin Nenitzescu ( 1902-1970) (Friedel-Crafts reaction, first to synthesize Main research centers: cyclobutadiene, oxidations of aliphatics with chromiun oxidants, Nenitzescu indole synthesis) Prague Institute of Chemical Technology; Prof. Alexandru Balaban (born 1931) (currently at UT, Austin) (theoy of aromaticity, pioneer of the Institute of Organic Chemistryvand Biochemistry (Prague) chemical graph theory)

Active researchers: Active researchers: not so much in organic chemistry... more in inorganic and analitical 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. Bulgaria

Slovakia Main reseach centers: Bulgarian Academy of Sciences, Institute of Organic Chemistry Main research centers: Plovdiv Univ Slovak Academy of Sciences; Institute of Organic Chemistry; Active researchers: Prof. Vladimir Dimitrov - organometallic chemistry, sythesis of asymmetric Slovak Technical Univ ligands

Main areas of research: sugars chemistry... Left uncovered.... Hungary(!!), Croatia(!), Serbia(!), Macedonia, Bosnia, Moldova, Albania, Russia(!!!!) 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