Ugi-Smiles Metathesis Approach to Pyrimido Azepines

Significance

Reported is a four-component coupling reaction (4-CC) of allyl amines, 5-allyl or homoallyl-4-hydroxypyrimidines (substituted at the 2- and 6-positions), aldehydes, and isonitriles. The molecular diversity of the Ugi-Smiles condensation product (see review below) can be rapidly increased, in this case, by olefin ring-closing meta­thesis (RCM). The presence of a heteroatom close to the reaction site was necessary for the occurrence of the Ugi-Smiles condensation. Development of a one-pot procedure could not be achieved, presumably due to degradation of the ruthenium carbene by residual isocyanide (B. R. Galan et al. Org. Lett. 2007, 9, 1203). Application of uracil and purine derivatives in the 4-CC reaction is currently being investigated. Elevated temperature and long reaction times were required to obtain moderate to good yields of the RCM products.