Synthesis of α-heterofunctionalized carbonyl compounds <i>via</i> Brønsted acid-catalyzed oxygenative coupling of ynamides

Abstract

Bronsted acid-catalyzed addition of pyridine-N-oxides to ynamides forms N-enoxypyridinium ions that are functionally equivalent to alpha-carbonyl cations. The mild oxidation conditions in this protocol are compatible with a range of heteroatom nucleophiles that are basic and/or easily oxidized. This umpolung approach allows for the introduction of unmodified heteroatom nucleophiles at the alpha-carbon and, importantly, the imide group in the product can be readily transformed into a variety of potentially useful esters and amides.

Brønsted acid-catalyzed addition of pyridine-N-oxides to ynamides forms N-enoxypyridinium ions that are functionally equivalent to α-carbonyl cations. The mild oxidation conditions in this protocol are compatible with a range of heteroatom nucleophiles that are basic and/or easily oxidized. This umpolung approach allows for the introduction of unmodified heteroatom nucleophiles at the α-carbon and, importantly, the imide group in the product can be readily transformed into a variety of potentially useful esters and amides.