N-Insertion of Diazonium Salts Into Ketone Derivatives

Abstract

We report a new oxidative nitrogen insertion into cyclic ketones using readily available diazonium salts. In the case of indanones, the reaction is promoted by auto-catalytically generated Br & oslash;nsted acid and proceeds via sequential alpha-diazenylation and ring expansion through an N-iminoaziridinium intermediate. For less alpha-acidic ketones, a complementary strategy employing silyl enol ethers was developed: catalyzed by HNTf2, efficient nitrogen insertion occurred into silyl enol ethers derived from a broad range of four- to seven-membered cyclic ketones. The resulting N-aminoamides exhibit broad synthetic utility in various downstream transformations. Notably, a ring expansion, followed by N & horbar;N bond cleavage offers a powerful tool for skeletal editing, converting indanones into isoquinolinones, as demonstrated by the scaffold modification of donepezil.