Presentation on theme: "Iron-catalyzed Cross Coupling reactions: From Rust to a Rising Star Weijun Liu."— Presentation transcript:
Iron-catalyzed Cross Coupling reactions: From Rust to a Rising Star Weijun Liu
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.
Iron: A More Practical Alternative 1.Iron is one of the most abundant metals on earth. (5.6% of earth’s crust. 4th most abundant element after oxygen, silicon, and aluminum. Nickel is %, palladium is %, gold is % of Earth’s 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
Content: 1.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
1.Early Examples J. Kochi, J. Am. Chem. Soc. 1971, 93, 1487
Kochi, J. J. Org. Chem. 1976, 41, 502
NMP as cosolvent Cahiez, G. Synthesis 1998, Alkenyl Derivatives as Substrates
Cahiez, G. Synthesis 1998, 1199
Cahiez, G.; Knochel, P. Synlett 2001, %
3. Aryl Derivatives as Substrates Furster, A. Angew. Chem., Int. Ed. 2002, 41, 609
Proposed Formal Catalytic Cycle
4. Alkyl Derivatives as Substrates Furster, A. Angew. Chem., Int. Ed. 2004, 43, 3955
Only tertiary halides and alky chlorides were found be inert.
Nakamura, E. J. Am. Chem. Soc. 2004, 126, 3686
Hayashi, T. Org. Lett. 2004, 6, 1279
Cossy, J. Angew. Chem., Int. Ed. 2007, 46, 6521
X = N, O, S Li, Z.-P. Angew. Chem., Int. Ed. 2008, 47, 7497
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.