Functionalizationof OrganicMolecules byTransition-Metal ... · Functionalizationof OrganicMolecules...
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Functionalization of Organic Moleculesby Transition-Metal-CatalyzedC(sp3)-H Activation
Rodolphe Jazzar, Julien Hitce, Alice Renaudat, Julien Sofack-Kreutzer, and Olivier Baudoin
Vorgetragen im MCII-Seminar am 27.10.2011
von Stefanie Auras und Carina Ammerlahn
Chem. Eur. J. 2010, 16, 2654 – 2672
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Gliederung
� Grundlagen
� C-H Aktivierung
� Mechanismen
� Inner-Sphere
� Outer-Sphere
� Ausblick
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Funktionalisierung: Grundlagen
� Was ist Funktionalisierung?
FG1 = HalFG2 = FG = C-R, O-R, C-N,…
C-H Funktionalisierung
Traditionelle Funktionalisierung
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Funktionalisierung: Grundlagen
� Warum Übergangsmetall-katalysierte
Funktionalisierung?
� Schnellere und ökonomischere
Synthesewege
� Bessere Kontrolle über den Reaktionsverlauf
� Effizientere Nutzung der Alkanressourcen
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C-H Aktivierung
� Allgemeine Definition:
Komplexbildung in der die C-H-Bindung direkt
mit einem Metal oder Katalysator interagiert;
meist mit einer C-M-Zwischenstufe und ohne
radikalischen oder ionischen Zwischenprodukten
Robert G. Bergman, Nature 2007, 446, 391 - 506
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C-H Aktivierung
� Präzisere Definition:
Bildung einer C-M-Bindung durch Spaltung einer C-H-
Bindung
� Entstehung eines Metall-Kohlenwasserstoff-Komplex
Robert G. Bergman, Nature 2007, 446, 391 - 506
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Funktionalisierungsmechanismen
� Inner Sphere-Mechanismus
� Outer Sphere-Mechanismus
C H C [M]C X
CH
[M] [M]
XX
C
[M]
X[M]
CX[M]
H
C XH
H
X
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Funktionalisierungsmechanismen
� Inner Sphere-Mechanismus
� C-H Aktivierung
� Organometallische Spezies wird gebildet
(H-Abstraktio
n)
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Problematik der C(sp3)-H Bindung
� Unreaktiv
� Paraffin: Latein parum affinis »wenig reaktionsfähig«
� gesättigte, lokalisierte σ-Bindungen
� Bindungsenergie: 418 kJ/ mol
� nicht Acide
� pks-Wert > 35
� Regioselektivität & Chemoselektivität
� Wechselwirkung zwischen C-H-Bindung und ÜM muss
initiiert werden
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Heteroatom-dirigierteC-H Aktivierung
� Die dirigierende Gruppe ermöglicht die Koordinationdes ÜM- Katalysators an das Substrat.
DG = -COOH, NR3Y = z. B. OrganoboranreagentienFG = Einzuführendes Molekül
- Regioselektiv � 5-6-gliedriger Metallazyklus- C-C, C-Si, C-O, C-Hal Bindungen
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Heteroatom-dirigierteC-H Aktivierung
� C-C Kupplung
� Reaktion:
Ruthenium-kathalysierte C-H Aktivierung mit Dihydropyrrol als dirigierende Gruppe
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Heteroatom-dirigierteC-H Aktivierung
� C-C Kupplung
� Mechanismus:
S. J. Pastine, D. V. Gribkov, D. Sames, J. Am. Chem. Soc. 2006, 128, 14220 – 14221.
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Heteroatom-dirigierteC-H Aktivierung
� C-O Kupplung
(Lactonbildung)
� Reaktion:
Platin(II)-katalysierte C-H Aktivierung
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Heteroatom-dirigierteC-H Aktivierung
� C-O Kupplung
(Lactonbildung)
� Mechanismus:
D.-H. Wang, X.-S. Hao, D.-F. Wu, J.-Q. Yu, Org. Lett. 2006, 8, 3387 – 3390
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Mehrfachbindungs-dirigierteC-H Aktivierung
� C-C Doppel- oder Dreifachbindungen als
dirigierende Gruppe
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Mehrfachbindungs-dirigierteC-H Aktivierung
� Allylische C-H Aktivierung
� Reaktion:
� Reaktion allg.:
Angew. Chem. Int. Ed. Eng. 1982, 21, 366 –367
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Mehrfachbindungs-dirigierteC-H Aktivierung
� Allylische C-H Aktivierung� Reaktion:
� Mechanismus:
Angew. Chem. Int. Ed. Eng. 1982, 21, 366 –367
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Oxidative-Addition-dirigierteC-H Aktivierung
� Oxidative Addition:
Bildung neuer M-A & M-B Bindungen
� Metallinsertion
� Koordinationszahl & Oxidationsstufe um 2 erhöht
� Reduktive Eliminierung:
umgekehrter Vorgang; Bildung einer neuen A-B Bindung
� KZ & OZ um 2 erniedrigt
� in katalytischen Reaktionen führt sie zur Produktbildung
http://wwwuser.gwdg.de/~nmoesch/pdfs/metallorganik/Kapitel4.pdf (Georg-August-Universität Göttingen)
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Oxidative-Addition-dirigierteC-H Aktivierung
X [M]
H
H
R
R
R H
R FG
R
n n
n
n
n
nX= Austrittsgruppe
[M], Base
Base-H-X
Y-FG
Insertion
ReduktiveEliminierung
beta-Eliminierung
Trans-metallierung
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Oxidative-Addition-dirigierteC-H Aktivierung
� Insertion
� Reaktion:
J. L. Portscheller, S. E. Lilley, H. C. Malinakova, Organometallics 2003, 22, 2961 –2971
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Oxidative-Addition-dirigierteC-H Aktivierung
� Intermolekulare C-C
Kupplung
� Reaktion:
Indan-Synthese durch Palladium(0)-katalysierte C-H Aktivierung
CN
HBr
NC
Me
PH2F
F- TOTP=50%
single-Diastereoisomer
Pd(OAc)2 (5 mol%),
F-TOTP (20 mol%)
K2CO3, DMF, 100°C
3
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Oxidative-Addition-dirigierteC-H Aktivierung
� Mechanimus:
J. Hitce, P. Retailleau, O. Baudoin, Chem. Eur. J. 2007, 13, 792 – 799
PdII
PdII
BrR2
PdII
R3
Alk R1
Br
Alk R1H
R3
R2H
K2CO3
KBr, KHCO3
oder
Palladazyklus-
Bildung
Oxidative
Addition
Reduktive
Eliminierung
(R2 nicht 0 )
Pd0
R3
Alk R1
R2
H
Alk R1H
R2
R3
R2
H
R3
AlkR1
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Tandem C(sp2)-H / C(sp3)-H Aktivierung
� Reaktion:
Palladium(II)-katalysierte Tandem-Aktivierung
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Tandem C(sp2)-H / C(sp3)-H Aktivierung
� Mechanismus:
B. Liegault, K. Fagnou, Organometallics 2008, 27, 4841 –4843
H2O
HX, O2
PdX2
+ HX
- HX
- HX
Pd0Pd
schwarz
Reduktive
EliminierungC(sp3)-H
Palladazyklus-
Bildung
(langsam)
Katalysator-
regeneration
Verlust
N
N
N
N
H
Ar
H
O
R
O
Ar
O
RPdX
O
H
Pd
Ar
O
R
OAr
O
R
O
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Funktionalisierungsmechanismus
� Outer-Sphere-Mechanismus:
� Koordinationschemie
� C-H-Insertion, C-H-Oxidation
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Funktionalisierungsmechanismus
� Outer-Sphere-Mechanismus:
� Metal-Carbenoid Funktionalisierung
MLn
MLn
R2
R1
N2
R2
R1
N2
C
R2
H
R1
CH
Huw M. L. Davies & James R. Manning, Nature 2008, 451, 417 - 424
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Zusammenfassung & Ausblick
� C-H Bindung als funktionelle Gruppe
� Atom- und Kosteneffizienter Ansatz für Synthese
(von komplexen organischen Gerüsten)
� Wenig erforschtes Gebiet
� Viele Mechanismen noch ungeklärt
� Reaktionsbedingungen verbessern