The use of Smiles rearrangement in Ugi- and Passerini-type couplings with electron-deficient phenols allows very straightforward multicomponent formation of O-aryl- and N-arylamides. Best yields were observed with the highly activated o- and p-nitrophenols, salicylic derivatives giving adducts in lower yields. The scope of these new reactions is further increased by the successful couplings of heterocyclic phenols such as hydroxypyridines and hydroxypyrimidines.

The three-component addition of isocyanides to phenol derivatives and aldehydes proceeds easily in methanol to form O-arylated compounds in a new Passerini-type reaction. The key step of the conversion lies in an irreversible Smiles rearrangement of intermediate phenoxyimidate adducts. It represents the first use of a Smiles rearrangement in a Passerini reaction.

New heterocyclic scaffolds can be easily prepared by the coupling of heteroaromatic phenols (pyridines, pyrimidines) with carbonyl compounds, amines, and isocyanides. This transformation related to the Ugi reaction probably involves a Smiles rearrangement. The scope of this methodology is further extended by the successful use of heterocyclic thiols to form highly functionalized thioamides.

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Treatment of activated phenols with carbonyl compounds and isocyanides results in new, straightforward formation of O-arylamides via Passerini-type coupling and subsequent Smiles rearrangement. Addition of primary aliphatic or benzylic amines to the reaction mixture leads to N-arylamides. The success of these new reactions is strongly dependent on the phenol. -(EL KAIM*, L.; GIZOLME, M.; GRIMAUD, L.; OBLE, J.; J. Org. Chem. 72 (2007) 11, 4169-4180; Lab. Chem. Procedes, Ec. Natl. Super. Tech. Av., F-75015 Paris, Fr.; Eng.) -Jannicke 39-053