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

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(sp(3))-rich polyheterocycles of relevance to medicinal chemistry.

Automated summary

TFA promotes deprotection of O-Ts activated N-Boc hydroxylamines, leading to aminofunctionalization-based polycyclizations of tethered alkenes. The method enables a range of intramolecular alkene anti-1,2-difunctionalizations, including diamination, amino-oxygenation, and amino-arylation. It offers a predictable platform for accessing diverse C(sp(3))-rich polyheterocycles relevant to medicinal chemistry.