Oxidative Coupling.ppt

Oxidative Coupling Scott Dufour Oxidative coupling of aromatic or heterocyclic compounds provides a method for creating aryl-aryl bonds Sometimes, it can be cheaper faster or easier than palladium based routes1 Continual advances in the nature of the oxidant and precisely defined reaction conditions have led to increasing levels of control upon C-C bond formation Chemoselective C-C vs. C-O bonding, regioselective bonding and stereoselective biaryl bond formation can be now be achieved in many well defined systems Oxidants Most recently, the hypervalent iodine complexes: phenyliodine (III) diacetate (PIDA), and phenyliodine(III) bis(trifluoroacetate) (PIFA) have been applied leading to an efficient , highly regioselective, mild non toxic alternative to heavy metals Vanadium Complexes (VOCl3, VOF3), Thallium and Lead have been found to be reliable oxidative coupling agents; prevented over-oxidations, and enhanced regio selectivety of C-C bond formation between aryl rings Iron (III) reagents were among the first tested and still have a wide following today; in the synthesis of triphenylenes it has been found the FeCl3 offers the best route of synthesis to these wide range of systems Hypervalent Iodine2 Intramolecular biaryl formation using tether strategy has been demonstrated The key is to use BF3* Et2O to enhance the electrophilicity of the iodine reagent Mechanistic View Evidence supports the formation of a single electron transfer complex2 Natural product chemistry led to the coupling of a tricyclic compound (norbelladine derivative) which illustrates the mechanism of using a phenolic substrate for oxidative coupling3 It was observed that only (CF3)2CHOH at -40 C worked well (70% yield), solvents like CH3CN, benzene, CH2Cl2 gave unsatisfactory results (less than 50% yield)3 Vanadium4 Uang and co-workers have published a catalytic version of Vanadium Oxidative coupling, where dioxygen oxidizes V(IV) to V(V) without interfering