Copper-Catalyzed Intramolecular Electrophilic Carbofunctionalization of Allylic Amides

摘要

Allylic amides and their derivatives represent a versatile class of nitrogen-containing building blocks, the bifunctional nature of which has enabled a diverse array of transformations and established them as strategically important molecules in chemical synthesis. Particularly useful are reactions where an electrophile activates the carbon-carbon double bond towards attack of the pendant oxygen atom of the amide carbonyl group to form either a five or six-membered ring heterocycle, depending on the mode of cyclization (Scheme 1 a).Most of these reactions are triggered by heteroatom electrophiles, often activated by a catalyst, and result in the formation of a carbon-oxygen and a carbon-heteroatom bond. It is, however, surprising that the related electrophilic carbofunctionalization process is rare. One possible reason for this is the lack of suitable carbon electrophiles that can activate the carbon-carbon double bond of the allylic amide. The development of Pd-catalyzed oxyarylation and aminoarylation reactions, in particular by Wolfe and co-workers, as well as related Pd, Cu,and Au-catalyzed processes have provided an alternative approach to related alkene difunctionalization and can be applied to derivatives of the generic allylic amine framework. Despite these advances, the development of novel methods that catalytically generate carbon electrophiles capable of activating alkenes to nucleophilic attack remains a challenge; the solution to this challenge would be of significant use in complex molecule synthesis.