Unexpected Stereoselective Access to 2-Aminooxazolines from Propargyl Ureas by Silver Salts under Mild Conditions

Propargyl ureas can lead to a range of possible heterocyclic compounds, mainly depending on the employed catalyst. Silver salts are known to promote the N-5-exo-dig cyclization mode to imidazolidinone derivatives. Conversely, a versatile and stereoselective O-5-exo-dig cyclization of propargyl ureas to 2-aminooxazolines by Ag(I) catalysis is here disclosed. Good to excellent yields and complete stereoselectivity of the external double bond have been achieved under milder reaction conditions (50-60 degrees C). A one-pot protocol starting from the corresponding propargylic amines and isocyanates has been developed as well. N,N'-Dipropargyl ureas underwent a uncommon O-5-exo-dig/N-5-endo-dig double cyclization sequence. Finally, insights into the tautomeric equilibrium of 2-aminooxazoles and on their relative reactivity are provided.

Automated summary

A new method for the transformation of propargyl ureas to 2-aminooxazolines using Ag(I) catalysis is disclosed in this article, providing good yields and complete stereoselectivity. A one-pot protocol starting from propargylic amines and isocyanates has also been developed. Insights into the tautomeric equilibrium and relative reactivity of 2-aminooxazoles are provided.