Non-Metal Catalyzed Transformations of Ynamides: Synthesis of α-Haloenamides and α-Ketoamides

Abstract

Ynamides are useful precursors to keteniminium ions that is versatile reactive intermediates for organic reactions. Over the past decade, a wide range of nucleophiles have been introduced to α-position of activated keteniminium ions generated from the protonation of ynamides. Herein, we investigated two catalytic modes of activation, namely by Brønsted acid and halonium reagents. In our previous study, keteniminium ions generated from Brønsted acid-catalyzed activation underwent a sequential oxidation by pyridine-N-oxides, followed by Friedel-Craft addition of nucleophiles. In sharp contrast, similar intermediates generated from weaker carboxylic acids induced the chemoselectivity change, leading to α-halogenation from halogenated solvents leading to α-haloenamides. Kinetic analysis revealed that a reversible formation of halonium adduct, followed by a rate-limiting attack of pyridine-N-oxides. We also compared the oxidation of ynamides using catalytic amount of halonium reagents. In contrast to Brønsted acid catalysis, N-oxide adducts from iodonium activation displayed a change of chemoselectivity, leading to over-oxidation affording α-ketoamides.