New developments in iron-catalyzed carbon-carbon bond forming reactions
The goal of this thesis is to develop new carbon-carbon bond forming reactions using inexpensive and simple coupling partners like aryl halides (pseudohalides), sulfonyl derivatives, Grignard reagents, alkenes and alkynes with metal catalysis, preferably under environmental friendly conditions. A brief review of different cross-coupling reactions is presented applying noble metal catalysts like palladium and nickel. The importance of sustainability and hence the development of alternative iron-catalysis is discussed. The history of iron-catalyzed cross-coupling reactions and their applications to the synthesis of natural products, significant new developments in the field are visited. On our side, we have shown that 2-methylpropene-, prop-2-ene-, 1-methylprop-2-ene- and but-2-enesulfonyl chlorides can be used as electrophilic partners in palladium-catalyzed desulfinylative C-C cross-coupling reactions with both hard and soft nucleophiles. Alk-2-enesulfonate esters can also be used as electrophilic partners in allylic arylations and allylic alkylations. The regioselectivity of the reaction depends on the nature of the catalyst. With PdCl2(PhCN)2, (E)-crotylderivatives are formed with high regioselectivity using either 1-methylprop-2-ene- or but-2-enesulfonyl chlorides. We found also the alk-2-enesulfonyl chlorides that are electrophilic partners in palladium-catalyzed C-C coupling reactions can also be used as nucleophilic partners towards carbonyl compounds by Umpolung. In the presence of a catalytic amount of palladium and a transmetallating agent such as diethylzinc, sulfonyl chlorides can be coupled both with aldehydes and ketones to form homoallylic alcohols in good yields. In the case of unsymmetrical sulfonyl chlorides, regioselectivity depends on the polarity of the solvent and generates selectively products of γ-addition. Most useful is our discovery of conditions permitting the desulfinylative C-C cross-coupling of inexpensive alkanesulfonyl chlorides and Grignard reagents. Above 65 °C, the iron-catalyzed reaction generates products of C-C coupling rather than sulfones. It does not require any expensive and/or toxic ligand. This procedure was also applied to the ligand free iron-catalyzed couplings of alk-2-enesulfonyl chlorides with aromatic and aliphatic Grignard reagents. We have also discovered the synergic effect of iron and copper salts in palladium-free Sonogashira-Hagihara cross-coupling reaction of a wide range of aryl iodides, aromatic and aliphatic alkynes. Together with Dr. R. Loska we have studied the iron-catalyzed Mizoroki-Heck cross-coupling reaction with styrenes. In the presence of iron(II) chloride and potassium tert-butoxide in dimethyl sulfoxide, aryl and heteroaryl iodides undergo stereoselective Mizoroki–Heck C-C cross-coupling reactions with electron-rich alkenes at 60 °C giving the corresponding (E)-alkenes. The best yields were obtained upon addition of a ligand such as proline or picolinic acid. Aryl bromides and pyridinyl bromides are also coupled with styrenes but in lower yields. Finally, we have explored iron-catalyzed C-H activation. Ligand and solvent free-conditions have been developed for the iron-catalyzed oxidative C-C cross-coupling of tertiary amines and terminal alkynes. FeCl2 catalyzes the coupling to generate propargylamines using tert-butylperoxide as oxidant. High chemoselectivity was observed for the aminomethyl group and was attributed to a steric factor.
Keywords: Iron-catalysis ; Palladium-catalysis ; Desulfinylative coupling ; Kumada coupling ; Sonogashira-Hagihara coupling Mizoroki-Heck coupling ; Oxidative coupling ; Catalyse au fer ; Catalyse au palladium ; Couplage désulfitant ; Couplage de Kumada ; Couplage Sonogashira-Hagihara ; Couplage Mizoroki-Heck ; Couplage oxydantThèse École polytechnique fédérale de Lausanne EPFL, n° 4517 (2009)
Programme doctoral Chimie et Génie chimique
Faculté des sciences de base
Institut des sciences et ingénierie chimiques
Laboratoire de glycochimie et de synthèse asymétrique
Record created on 2009-09-03, modified on 2016-08-08