Studies towards a Nickel-Mediated Decarboxylative Coupling

Organometallic reactions are important in organic synthesis and are versatile in creating new C-C bonds. In the past decade, late-transition-metal catalysis has gained increasing attention culminating in the 2010 Nobel Prize in Chemistry award for three seminal palladium catalyzed reactions. However, the commodity metal nickel is more economical and desirable than the other d10 elements, such as Pd and Pt. As chemistry is a continuously evolving science, the concepts of green chemistry and atom economy have gained attention. Decarboxylative coupling reactions, due to their environmental friendliness and ease of access, have been favored in recent years as alternatives. A carboxylic acid or carboxylate functionality is employed to replace classic organometallic nucleophiles. Intramolecular decarboxylative reactions have been developed by Steglich[1] and Myers[2][3] and decarboxylative cross-coupling reactions were investigated by Becht[4][5], Gooßen[6][7] and Forgione[8]. However, all these decarboxylative reactions are palladium mediated reactions. The proposal is to develop Nickel catalyzed decarboxylative coupling reactions. Percec et
al. [9] investigated Nickel catalyzed Suzuki-Miyaura typed cross coupling of aryl arenesulfonates or aryl mesylates with arylboronic acids. Scott et al. [10] also found that Nickel catalyzed organozincs can be employed in cross coupling with iodides. Therefore we will investigate the carboxylate functionality as nucleophiles to replace organometallic nucleophiles. Since the development of Nickel-mediated decarboxylative coupling reactions is at an early stage, the
current focus is on intramolecular reactions, Electron rich hetero-aromatic pyrrole carboxylic acids is chosen as starting material to create the nucleophile replacement. The pyrrole carboxylic
acids can be prepared from ?-azidoacetate and ?,?-unsaturated aldehyde through aldocondensation and reductive annulation[11][12]. Catalytic nickel complexes and stoichiometric reductants such as zinc(0) powder will be used to enable a full nickel catalyzed cycle to enable the decarboxylation to occur.

Faculty Supervisor: 
Pat Forgione
Partner University: