A diastereoselective cobalt-mediated synthesis of benzopyrans using a novel variation of an intramolecular Nicholas reaction in the key cyclisation step: optimisation and biological evaluation1

Abstract

A range of novel intramolecular cyclisation reactions between an organocobalt stabilised cation and a trisubstituted alkene have been accomplished that provide a concise route for the diastereoselective synthesis of a range of functionalised benzopyrans. In addition to the usual Lewis acids employed in the Nicholas reaction our studies have identified several other reagents for effecting the cyclisation reaction. In some examples sub-stoichiometric quantities of Lewis acid were successfully employed. These studies were concluded with a biological evaluation of specific derivatives, conducted by comparing their activity with the antihypertensive agent cromakalim 2, a drug whose mode of action is known to occur via the modulation of potassium channel activity.