Cobalt-catalyzed alkenylation and alkylation of heteroarenes.
Date of Issue2013
School of Physical and Mathematical Sciences
Heteroarene moieties are present in a variety of biologically active natural products, pharmaceuticals and electroactive materials. Hence, the development of efficient synthetic methods for functionalized heteroarenes has been an important issue for synthetic chemists. In this context, C–C bond forming reactions via activation of heteroaromatic C–H bonds are particularly attractive. This thesis describes the development of alkenylation and alkylation reactions of heteroarenes catalyzed by cobalt complexes. Following a brief overview of major developments in this area (Chapter 1), Chapter 2 describes alkenylation of an azole C(2)–H bond with an internal alkyne using a cobalt-diphosphine catalyst. The reaction features mild conditions and high chem-, regio-, and stereoselectivities. C2-alkenylation has also been achieved for indole bearing an N-pyrimidyl directing group and internal alkynes with the aid of a cobalt-pyridylphosphine catalyst (Chapter 3). The reaction proceeds at room temperature to afford C2-alkenylated indoles in high yield with excellent stereoselectivity, showing broad scope with respect to indoles and alkynes. N-pyrimidylindole also participates in C2-alkylation with vinylsilane in the presence of a cobalt-bathophenanthroline catalyst under mild conditions (Chapter 4). Finally, Chapter 5 describes intramolecular C2-alkylation of an alkene-tethered indole through directed C–H activation, which is uniquely promoted by a cobalt-NHC catalyst. The reaction affords dihydropyrroloindole or tetrahydropyridoindole derivatives, many of which have not been accessed by other synthetic methods.