A Stereospecific Alkene 1,2-Aminofunctionalization Platform for the Assembly of Complex Nitrogen-Containing Ring Systems

Abstract

TFA promoted deprotection of O−Ts activated N-Boc hydroxylamines triggers aminofunctionalization-based polycyclizations of tethered alkenes. The processes involve intramolecular stereospecific aza-Prilezhaev alkene aziridination in advance of stereospecific C−N cleavage by a pendant nucleophile. Using this approach, a wide range of fully intramolecular alkene anti-1,2-difunctionalizations can be achieved, including diaminations, amino-oxygenations and amino-arylations. Trends associated with the regioselectivity of the C−N cleavage step are outlined. The method provides a broad and predictable platform for accessing diverse C(sp3)-rich polyheterocycles of relevance to medicinal chemistry.