Iron-catalyzed Cross Coupling reactions:

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Iron-catalyzed Cross Coupling reactions From
Rust to a Rising Star
Weijun Liu
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Transition metal catalyzed cross couplings have
seen incredible advances and applications, have
wide scope and compatibility. But..typically use
palladium and nickel which are generally toxic
and expensive. Expensive and/or sensitive
ancillary ligands are required. Alkyl iodides,
bromides and triflates are best. With special
ligands alkyl chlorides may be used.
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Iron A More Practical Alternative

• Iron is one of the most abundant metals on earth.
  (5.6 of earths crust. 4th most abundant element
  after oxygen, silicon, and aluminum. Nickel is
  0.0084, palladium is 0.0000015, gold is
  0.0000004 of Earths continental crust.)
• 2. Cheap
• PdCl2 4005/150g 26.70/g
• NiCl2 98.40/250g 0.39/g
• FeCl3 30.40/1kg 0.03/g
• 3. nontoxic
• Prevalent in biological systems

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• Content
• Early Examples
• 2. Alkenyl Derivatives as Substrates
• 3. Aryl Derivatives as Substrates
• 4. Alkyl Derivatives as Substrates
• 5. O, N, S-Arylation
• 6. Oxidative Cross-coupling

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• Early Examples

J. Kochi, J. Am. Chem. Soc. 1971, 93, 1487
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Kochi, J. J. Org. Chem. 1976, 41, 502
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2. Alkenyl Derivatives as Substrates
NMP as cosolvent
Cahiez, G. Synthesis 1998, 1199
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Cahiez, G. Synthesis 1998, 1199
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60
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Cahiez, G. Knochel, P. Synlett 2001, 1901
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3. Aryl Derivatives as Substrates
Furster, A. Angew. Chem., Int. Ed. 2002, 41,
609
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Proposed Formal Catalytic Cycle
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4. Alkyl Derivatives as Substrates
Furster, A. Angew. Chem., Int. Ed. 2004, 43,
3955
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Furster, A. Angew. Chem., Int. Ed. 2004, 43,
3955
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Furster, A. Angew. Chem., Int. Ed. 2004, 43,
3955
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Only tertiary halides and alky chlorides were
found be inert.
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Nakamura, E. J. Am. Chem. Soc. 2004, 126, 3686
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Hayashi, T. Org. Lett. 2004, 6, 1279
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Cossy, J. Angew. Chem., Int. Ed. 2007, 46, 6521
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51
Chai, C.L.L. Adv. Synth., Catal. 2007, 349,
1015
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5. O, N, S-Arylation
Bolm, C. Angew. Chem., Int. Ed. 2007, 46, 8862
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Bolm, C. Angew. Chem., Int. Ed. 2007, 47, 586
Bolm, C. Angew. Chem., Int. Ed. 2008, 47, 2880
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6. Oxidative Cross-coupling
Iron-Catalyzed Homo-Coupling
FeI/FeIII or Fe0/FeII
Fe-II/Fe0
Cahiez, G. Org. Lett. 2005, 7, 1943
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Cahiez, G. J. Am. Chem. Soc. 2007, 129, 13788
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Oxidative Heterocoupling
Cahiez, G. Angew. Chem., Int. Ed. 2009, 43,
ASAP
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Iron-Catalyzed Direct Arylation through Directed
C-H Bond Activation
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Nakamura, E. J. Am. Chem. Soc. 2008, 130, 5858
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Iron-Catalyzed Chemoselective ortho Arylation of
Aryl Imines by Directed C-H Bond Activation
Nakamura, E. Angew. Chem., Int. Ed. 2009, 48,
ASAP
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Li, Z.-P. Li, C.-J. Angew. Chem., Int. Ed.
2007, 46, 6505
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X N, O, S
Li, Z.-P. Angew. Chem., Int. Ed. 2008, 47,
7497
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Summary
1. Iron catalysts activate alkenyl, aryl, and
alkyl derivatives. 2. Iron catalysts activate
aryl chlorides, triflates and tosylates under
ligand free conditions. 3. Iron-catalyzed
cross-coupling shows excellent functional group
tolerance. 4. Iron-catalyzed cross-coupling
needs only short reaction (typically 5-30 min)
time and are performed at low temperatures
(typically -20 oC to 0 oC). 6. Iron salts has
been successfully applied in the C-H bond
activation and oxidative coupling reactions But
the iron-catalyzed cross coupling is not nearly
as mature as its palladium and nickel
counterparts. And the reaction mechanisms are
needed to be proved.