new enamine - fluorinated diazoalkanes: synthesis and application · 2016. 3. 23. · 13 no...
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Fluorinated diazoalkanes:synthesis and application
Pavel Mykhailiuk2016
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World's largestproducer of building blocks
~100.000 compounds on stock(gram-scale)
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500 chemists 10 own buildings private company
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50 papers
www.enamine.net 5H. Gilman, R. G. Jones JACS, 1943, 1458.
Until 2006 CF3CHN2was rarely used in chemistry.
Ethyl diazoacetate is extremely popular (> 100 reactions).
T. Curtius Chem. Ber. 1883, 2230.
Liquid
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19F-label for Proline
2008
P. Mykhailiuk et al. Angew. Chem. Int. Ed. 2008, 5765.
19F
www.enamine.net 7P. Mykhailiuk et al. Angew. Chem. Int. Ed. 2008, 5765.
Synthesis of 19F-label for Proline
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Ar
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Advanced CF3-amines fordrug discovery
O. Artamonov et al. EurJOC 2014, 3592.
www.enamine.net 10O. Artamonov et al. EurJOC 2014, 3592.
Synthesis of CF3-amines
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CF3-cyclopropanation of alkenes
O. Artamonov et al. EurJOC 2014, 3592.P. Mykhailiuk et al. Synthesis 2008, 1741.P. Mykhailiuk et al. ACIE 2008, 5765.
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Do we need dry CF3CHN2 here?
Do we need to isolate it then?
CF3-cyclopropanation of alkenes
[3+2]-cycloaddition with alkenes
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No purification
Scalable (500 g)
one-pot, RT, no inert atmosphere, no catalysts,common solvents,no gaseous reagents,no side products,97% yield
[3+2]-cycloaddition with alkenes
E. Slobodyanyuk et al. EurJOC 2014, 2487.
www.enamine.net 14E. Slobodyanyuk et al. EurJOC 2014, 2487.
CF3-pyrazolines
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Bioaktive CF3-pyrazoles
www.enamine.net 16E. Slobodyanyuk et al. EurJOC 2014, 2487.
CF3-pyrazoles
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CF3
NH2
*HCl NaNO2CF3
N2
in situ-generated
CH2Cl2/H2ORT RT
EWG EWG
Base
EWG EWG
NHN
CF3
Japp-Klingemann reaction
17Unpublished results
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2014: unknown
www.enamine.net 19P. Mykhailiuk Chem. Eur. J. 2014, 4942.P. Mykhailiuk Beilstein J. Org. Chem. 2015, 16.
C2F5-pyrazolines
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C2F4H-pyrazoles
Unpublished results
www.enamine.net 21P. Mykhailiuk Chem. Eur. J. 2014, 4942; P. Mykhailiuk Beilstein J. Org. Chem. 2015, 16; P. Mykhailiuk Org. Biomol. Chem. 2015, 3438.
C2F5-pyrazoles
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2015: not usedproperly
T. Curtius Chem. Ber. 1898, 2490.
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CN-pyrazoles
P. Mykhailiuk EurJOC 2015, 7235.
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P. Mykhailiuk Chem. Eur. J. 2014, 4942. P. Mykhailiuk Beilstein J. Org. Chem. 2015, 16. P. Mykhailiuk Org. Biomol. Chem. 2015, 3438.P. Mykhailiuk EurJOC 2015, 7235.P. Mykhailiuk Angew. Chem. Int. Ed. 2015, 6558.
Scope
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2015: unknown
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In-situ generation of CHF2CHN2
non-aqueous conditions?
P. Mykhailiuk Angew. Chem. Int. Ed. 2015, 6558.
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CHF2-pyrazoles
P. Mykhailiuk Angew. Chem. Int. Ed. 2015, 6558.
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popular (> 4000 reactions)
2014:
in situ-generated RCHN2
>70 papers
2015: 2015:
2014:
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500 chemists
Alekseenko A.
Artamonov O.
Artemenko A.
Andrushko O.
Arkhipov A.
Arkhipov V.
Bilenko V.
Chalyk B.
Datcenko O.
Denisenko O.
Dmitriv U.
Druzhenko T.
Granat D.
Gorulia O.
Garbuz P.
Gavrilenko K.
Martirosov R.
Moroz U.
Mituk A.
Mikhalchuk V.
Gryshuk S.
Iminov R.
Komarov I.
Kokhan S.
Kondratov V.
Kubyshkin V.
Khutorianskii A.
Levchenko K.
Logvinenko V.
Ostapchuk E.
Pasternak A.
Parhomenko L.
Pervak I.
Pustovit U.
Radchenko D.
Savich V.
Scherbatiuk A.
Shyshlik O.
Slobodianuk E.
Tkachenko A.
Tkachuk G.
Tolmacheva N.
Tolmachev A.
Trofimchuk S.
Tverdokhlebov A.
Tymtsunik A.
Volochnyuk D.
Yakovenko N.
Yarmolchuk V.
Yarmoluk D.
Thank you!
Enamine: world's largest supplier of building blocks
2016