Copper-Catalyzed Alkene Aminoazidation as a Rapid Entry to 1,2‑Diamines and Installation of an Azide Reporter onto Azahetereocycles

A copper-catalyzed
aminoazidation of unactivated alkenes is achieved
for the synthesis of versatile unsymmetrical 1,2-diamine derivatives.
This transformation offers an effective approach to installing an
amide and an azide from two diffenent amino precursors onto both terminal
and internal alkenes, with remarkable regio- and stereoselectivity.
Mechanistic studies show that this diamination reaction proceeds via
a nucleophilic amino cyclization followed by an intermolecular C–N
bond formation using electrophilic azidoiodinane. This pathway differs
from previous azidoiodinane-initiated alkene functionalization, suggesting
new reactivity of azidoiodinane. Furthermore, this aminoazidation
reaction provides an efficient strategy to introduce azide, one of
the most useful chemical reporters, onto a broad range of bioactive
azaheterocycles, offering new opportunities in bioorthogonal chemistry
and biological studies. Rapid syntheses of 5-HT2C agonist,
(−)-enduracididine and azido-cholesterol derivatives demonstrate
broad applications of this method in organic synthesis, medicinal
chemistry, and chemical biology.