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".
"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/
http://www.espicom.com/prodcat2.nsf/Product_ID_Lookup/00000396?OpenDocument
- importantly, the health care system is run by the government, so obviously there is little impetus for significant R&D programs.
https://www.mckinseyquarterly.com/Pharmas_generics_opportunity_in_Central_and_Eastern_Europe_2186#
Organic Chemistry from the Eastern Bloc
Baran Lab GM
08/13/2011
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
Florina Voica
O
nBuLi,
SO2Ph
TMS
(+)DET, Ti(OiPr)4,
TBHP
1. TsCl, pyr
2. (nC9H19)2CuLi
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
OH
C9H19
O
O
(+)-disparlure
Tet. Lett. 1989, 30, 2845
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:
O
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.
Me
O
PhO2S
Me
1. L-selectride
2. N2H4
3. I2
H
HO
Me
OH
O
H
H
O
O
Me
O
Me
Me
1. LDA, MoOHPy
2. Ph3P • • O
H
Me
THPO
OH
THPO
J. Org. Chem. 1988, 53, 4855
H
H
Organic Chemistry from the Eastern Bloc
Me HO
Me
Me
iPr
H
THPO
80%
H
OMe
OMe
1.VO(acac)2, TBHP, 86%
2. mCPBA, 87%
3. TFAA, pyr, 87%
F3C
O
Me
Br
Me
THPO
Me
H
OMe
OMe
MeLi/Et2O -78 °C to rt
then
MeI, -78 °C to rt
60%
O
O
O
Me
Me
THPO
Me
Me
OH
Me
H
HO
H
Me
Me
Me
Me
Me
Me
OH
OH
HO
23-H-isocalysterol
(both diastereoisomers are NPs)
OMe
J. Org. Chem. 1995, 60, 1823
J. Am. Chem. Soc. 1995, 117, 1849
Organic Chemistry from the Eastern Bloc
Ph
+
N
83%
Cl
N
66%
N
SO2Ph
TBSO
O-
N+
+
X
TBSO
DBU
-TBSOH
MeO
-
NO2
-
NO2 R
TBSO
NO2
N
Me
MeO
NO2
CN
OMe
H
N
MeO
HN
NO2
CO2Et
Synthesis 1997, 1131
O
OAc
Me
Q+Y-org
+
Na+Y-aq
AcO
O
O
3B
MeO
OH
+
MeO
Me O
HO
RY
Na+OH-aq
PhCH-CNorgNa+int
+
Q+X-
+
int
PhCH-CN
org
org
Q+
OAc
OH
H2Oaq
Na+X-
+
org
MeO
BF3•Et2O
acetone, then H2O
75%
aq
Ph
PhCH-CNorgQ+org
+
R-Xorg
R
Q+X-org
+
CNorg
H
AcO
NaOH, MeOH
MeO
Na+
TsOAc
Ac2O,
70%
Me O
AcO
H
HO
- in situ generated organic anions:
+
Me O
Q+X-org
+
Q+X-org
RX
PhCH2CNorg
Florina Voica
O
Q+X-org
+
Me O
Me O
O
For a general review and applications see: Pure Appl. Chem. 2000, 72, 1399 and refs therein.
TMSCF3 (1.2 equiv)
OMe
OMe
OMe
KF(s) (1.5 quiv)
CAN (2.2 equiv)
Ph3SnF (0.3 equiv)
MeOH-H2O 4:1
90%
DCM, rt, 24h
N
CF3
+
N
CF
3
N
76%
BrPMB
PMB
J. Org. Chem. 2007, 72, 5574
H
H
H
OH
MeO
J. Org. Chem. 1975, 40, 3124, 3135
Me O
O
Me
O
HBr, AcOH
MeO
O
MeO
1. TiCl4
2. Zn, 85%
14-dehydroequilenin
Me O
Me O
HClO4
HBr
O
estrone
MeO
MeO
Tet. Lett. 1982, 23, 2411
Organic Chemistry from the Eastern Bloc
Baran Lab GM
08/13/2011
Me O
Me O
tBuCu, DIBAL
HMPA
O
57%
O
H
H
Br
HO
Me
Me
OH
Me
1. PDC, 65%
2. Wittig, 92%
3. LAH, 87%
Me
Me OH
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.
O
H
O
vit D3 metabolite
OH
H
H
J. Org. Chem. 1988, 53, 5534
OTBS
O
OH
OAc
H
H
O
TBSO
tBuCu, DIBAL
70%
O
7 steps
Me O
H
HO
Me O
Me O
Synthesis 1979, 41; Chem. Commun. 1983, 540; Synthesis 1985, 928.
1. mCPBA
2. Martin rgnt
90%
C5H11
OAc
OAc
1. N2H4, H2O2
2. SeO2
H
H
60%
H
Me
O
28%
O
1. 15 kbar, 2% Eu(fod)3
50 °C, Et2O
2. PPTS, rt, MeOH
80%, dr 16:1
NBocBzl
+
OH
H
Me
O
H
Me
O
H
H
OH
H
Me
+
O
O
major
OMe
O
J. Org. Chem. 1989, 54, 3759
purpurosamine B
Organic Chemistry from the Eastern Bloc
Baran Lab GM
08/13/2011
NBocBzl
Me
OMe
compactin
Me
NBocBzl
H
OMe
Tet. Lett. 1990,
31, 5599
H
O
O
OAc
H
O
J. Org. Chem. 1981, 46, 2230
Me
O
C5H11
OMe
Et
Me
1. MoO3, 30%H2O2
2. Ac2O, pyr
3. 10% Pd/C
24% overall
C5H11
OMe
H
OAc
1. Martin rgnt
2. KOH
15-20kbar
50-65 °C,
Et2O
O
H
90% (3 steps)
OAc
+
OAc
1. LAH
2. Ac2O
3. Martin rgnt
H
Florina Voica
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).
Me O
Br2
i-Bu2AlO
H
H
MeO
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.
1. conc HCl
2. Ac2O, AcOH, 85%
O
Cl
O
3. chiral resolution
Cl
O 4. SOCl
Me
KOH, MeOH
Me
2
80%
+
5. CH2N2, 87%
MeO
O
OMe
O
O
HO
Br
69%
CN
NO2
Damirone B
General reaction scheme:
- reactive inorganic anions:
org
CO2Et
H2,
MeO
PdCl2-Fe
48%
HN
Phase transfer catalysis:
O
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
N2
will generate organic anions; the organic mixture containg the organic reactants and the phase
transfer catalyst (source of lipophilic cations).
NO2
CN
Organic Chemistry from the Eastern Bloc
Baran Lab GM
08/13/2011
PhCH-CN
MeO
NO2
OMe
H
N
O
OMe
Me2SO4,
NaHCO3
83%
NO2
O
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.
SO2
OH
NO2
O
Ph
N
Me
CN
PhO
tBuOK, DMF
80%
σH complex
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).
N
hν
SO2
NO2 R
NO2 R
SO2
N
Me
N
N
Me
Acta Chem. Scand. 1992, 46, 689
OH
Y
Y
Ph
DBU
-TBSOH
SO2
N
Me
SO2
N
H+
Y
Y
NO
Ph
DBU
TBSCl
SO2
base
-HX
N
DBU
TBSCl
General reaction scheme:
base
solvent
SO2Ph
N
SO2Ph
Ph
OH
SO2Ph
NO2
N
Me
Ph
NC
Me
aq. NH4Cl
KOH, DMSO
N
Chem. Lett. 1987, 61
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.
X
DMDO,
H2O
Me
NC
Florina Voica
J. Org. Chem. 1998, 63, 4390
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.
R
tBuOK
DMF/THF
-70 °C
NO2
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.
Na+Y-aq
Me
TsOH/aq dioxane
H
Digitoxigenin
Baran Lab GM
08/13/2011
Br
Me
CHBr3-50%NaOH
CETRIMID
50%, dr 1:1
(separable)
Me
O
H
H
Br
Br
Me
Me
O
H
O
TMS
TBAF, H2O,
THF, rt
Me
1. DIBAL
2. TsCl, pyr
3. Superhydride
80%
O
Me O
Me
Br
Me
Br
H
EtO2C
Me
Me
93%
H
Florina Voica
CO2Et LDA/THF, -78 °C then
Br
TMS
Br
TMS
nBuLi, BF3•Et2O
Me
THPO
H
OH
OSitBuPh2
Me O
H
1. tBuNC, NaCNBH3
Bu3SnCl, AIBN
2. DHP
3. MeLi, PhH
Tet. Lett. 1991, 32, 531
Baran Lab GM
08/13/2011
THPO
Me O
OH
H
Me
OH
Me
N2H2
OH
TMS
PhO2S
O
Me I
H
LDA, THF
89%
TBAF
41%
H
OH
Me I
dr 3:1
OMs
Me
H2, Pd/C
OSitBuPh2
nBuLi
1. NaOMe, 40%
2. H2, Pd/SrSO3
Me
O
TMS
then MsCl
86% (over 2 steps)
H
O
Me O
O
HO
OSitBuPh2 TMS
O
Me
SO2Ph
OH
then HClO4, MeOH
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.
Florina Voica
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:
R1
O
N
O 1. CDCl3, rt,
1 atm, 6h, 42%
2. steps
•
+
OTMS
1 equiv
NBn
HO
3 equiv
OH
O
HO
Bn
O
OH
J. Org. Chem. 1986, 51, 2395
Tet. Lett. 1987, 28, 3035
M
+
R1
+
-O
O
N+
M
SiR3
M SiR3
M = Ru, Rh, Co
R = alkyl, aryl, alkoxy
R1 = alkyl, pheyl, OR, SiR3, -pyrrolidinone, carbazole
N
SiR3
H H
R1
O
O
H H
R1 H
H H
OBn
BnO
O
SiR3
H H
H SiR3
M
CuI (0.1 equiv),
TMG (2 equiv),
ACN, 44%
M H
SiR3
SiR3 R
N
O
CCl3
O
TMSO
O
Acc. Chem. Res. 2007, 40, 943
O
F
O
F
O
OBn
OBn
OH
Si
RuHClCO(PPh3)3 (1 mol%)
80 °C, 1h
85%
O
O
Si
O
H2O/HCl
88%
Si
Si
Si
Si
O
Si(OEt)3
N
N
TMSO
+
F
F
Angew. Chem. Int. Ed. 2006, 45, 8180
J. Org. Chem. 2011 ASAP
Organic Chemistry from the Eastern Bloc
Baran Lab GM
08/13/2011
Other accomplished polish chemists:
Me
-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) Ph
- 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
N
- 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
O
CsSO4F (2 equiv), rt
cyclohexane
77%
Br
F3C
CF3
Tet. Lett. 1990, 31, 3357
XeF2
105 °C, 2.5h
Ph
N
J. Org. Chem. 1992, 57, 5334
F
F
N
Me
+
Tet. Lett. 1990, 31, 775
30%
N
F
Me
F CsSO4F (1.3 equiv)
MeOH, 40 ° C
72%
N
O
OSO2F
O
N
N
O
F
Tetrahedron 1990, 46, 3093
OMe
Me
Me
Electrophilic fluorination with N-F reagents (Selectfluor, Accufluor)
F
O
F
N+
O
N+
(BF4
-)
N+
O
Selectfluor
solvent free
Me
(BF4-)2
2
Me
F
87%
F
OH
OEt
Accufluor
Selectfluor
solvent free
OEt
61%
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 rxn
conditions
HO
Tet. Lett. 2007, 48, 2671
Me O
Me O
Selectfluor (1.05 equiv)
H2O, 60 °C
74%
F
Org. Lett. 2004, 6, 4973
O
NHAc
F
F
+
NHAc
Accufluor (1.1 equiv)
ACN, 70 °C
+
28%
42%
F
30%
+
74%
Chem. Commun. 1996, 2247
Bull. Chem. Soc. Jpn. 1986, 59, 1659
F
F
1 : 3
Organic Chemistry from the Eastern Bloc
Baran Lab GM
08/13/2011
Main research centers:
National Academy of Sciences, Kiev
Kiev Polytechnic Institute
Karkow National Univ
Founding fathers:
too close to Russia, difficult to define..
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/CBr4
DCM, Et3BnNCl, 40 °C
44%
Br
I
NaOH, CHI3,
rt, 24h
92%
NaOH, CHI3,
rt, 24h
C5H12
92%
nPr
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
Et
I
+
4:1
Et
Kulinkovich reaction:
1. EtMgBr (2 equiv)
Ti(OiPr)4 (5-10 mol%)
Et2O, rt, 1h
2. 5% aq H2SO4, 5 °C
CO2Me
R
76-95%
I
Angew. Chem. Int. Ed. 1998, 37, 1895; 1999, 38, 2786
O
O
8
S
96%
HO
O
H2SO4
80 °C
MeMgBr
65%
93%
Me
CF3CO3H
TFA
80%
Org. Lett. 2009, 11, 3068
Baran Lab GM
08/13/2011
Me
O
OH
Main research centers:
Prague Institute of Chemical Technology;
Institute of Organic Chemistryvand Biochemistry (Prague)
C17H35
OH
8
Me
OH
72%
Me
Synlett 2003, 967
For more on red coupling, see Ian Young GM
Organic Chemistry from the Eastern Bloc
Czech Republic
Me
1. Ti(OiPr)5 (0.5 equiv)
iPrMgBr (2 equiv),
Et2O, rt
OH
2. H+, H2O
Me
Tet. Lett. 1998, 39, 1823
N2H4, KOH, 190 °C
7
7
O
3, 11 - dimethylnonacosan-2-one
OH
1. P, I2
150 °C
2. KOtBu,
DMSO
C17H35
Me
C17H35
Synthesis, 1989, 234
Chem. Rev. 2003, 103, 2597
8
Me
3. KOH, THF, 67%
Org. Lett. 2007, 9, 2541
R
1. ethyl stearate (1 equiv)
Ti(OiPr)4 (1 equiv)
C6H10MgBr (6 quiv)
C17H35
2. H+, H2O
OH
HO
56%
1. MeCO2Et (1.4 equiv)
Ti(OiPr)4 (1.4 equiv)
C6H10MgBr (7.1 equiv)
2. H+, H2O, 64%
p-TSA, DCM
NaH. DMSO
130 °C, 12h
96%
Florina Voica
Main research centers:
National Academy of Sciences of Belarus
Belorussian State Univ
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
50% NaOH/CBr4
DCM, Et3BnNCl, 40 °C
37%
O
N+
Cl
Selectfluor
1. Mg, Et2O
2. CS2
3. XeF2
Me
CsSO4F (1.1 equiv), ACN
rt, 1.5 h
84%
O
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
Florina Voica
70%
Prof. Branko Stanovnik (Ph.D, 1964)
- 583 publications - heterocyclic chemistry
O
TMSO
Si(OEt)3 RuHCl(CO)(PCy3) (1 mol%)
PhMe, 110 °C
92%
O
O
F3C
O
Si
J. Org. Chem. 2005, 70, 370
F
Ezetimibe
Si
Florina Voica
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:
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 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
2
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(!!!!)