The Elusive Paal–Knorr Intermediates in the Trofimov Synthesis of Pyrroles: Experimental and Theoretical Studies

We
have used isoxazolo­[3,4-b]­pyridin-3­(1H)-one and isoxazolo­[3,4-b]­quinolin-3­(1H)-one as “masked” heterocyclic hydroxylamines
to generate Paal–Knorr intermediates of the Trofimov pyrrole
synthesis. The previously inaccessible intermediates, trapped by ethyl
propiolate, were obtained by reacting corresponding isoxazolones with
4-fold excess of ethyl propiolate under basic conditions at ambient
temperature, and characterized by means of IR and NMR spectroscopic
data as well as by single crystal X-ray analysis. Quantum chemical
calculations of a [3,3]­sigmatropic rearrangement of the N,O-divinyl hydroxylamines to corresponding imino-aldehydes
(Paal–Knorr intermediates) revealed that this reaction proceeds
via chairlike transition state and is exothermic.