Copper-catalysed synthesis of 5- and 6- membered nitrogen-containing heterocycles

Nitrogen-containing heterocycles are an important structural motif, prevalent in both nature and medicine. N-Heterocycles can be found at the core of numerous biologically active molecules resulting in a huge amount of attention focussed on the novel synthesis of these privileged motifs from both academic and industrial researchers alike. In recent years the importance of developing efficient, “green” and cost effective routes to medicinal agents has become increasingly at the forefront of modern research.

In 2009 the Taylor group reported the successful synthesis of oxindole heterocycles via a copper(II)-mediated approach. Following on from this research, the development of a high-yielding and green set of conditions is described for the synthesis of oxindoles (I). The successful application of these conditions to both 5-membered N-heterocycles (Chapter 2) and 6-membered N-heterocycles (Chapter 3) is described including thio-oxindoles (II), 3,4-dihydroquinolin-2(1H)-ones (III) and 2-quinolinones (IV).

Reported, is the application of this methodology to biologically active molecules, including formal synthesis of the oxindole-containing drug Satavaptan (V) (Chapter 2.2), the first reported total synthesis of two biologically active, 3,4-dihydroquinolin-2(1H)-one containing natural products (VI and VII) (Chapter 3.7) and efforts towards the total synthesis of the 2-quinolinone-containing drug candidate HOFQ (VIII) (Chapter 3.8).