Accessing skeletal diversity using catalyst control: formation of n and n + 1 macrocyclic triazole rings

Abstract

A regioselective intramolecular Huisgen cycloaddition was performed on various azido alkyne substrates giving rise to macrocyclic triazole rings. Using catalyst control, a common intermediate has been converted to two structurally unique macrocycles with either a 1,5- or a 1,4-triazole resulting in an n or n + 1 ring size. This is the first example of an intramolecular ruthenium-catalyzed Huisgen cycloaddition.

Scheme 1

Use of Huisgen cycloaddition for divergent pairing

Scheme 2

Substrate synthesis and intramolecular Ru-catalyzed cycloaddition

Figure 1

X-ray crystal structures of representative macrocyclic triazoles (4a and 5f)