N-Heterocyclic carbenes as ligands in palladium-catalyzed Tsuji–Trost allylic substitution

A Pd(0)-catalyzed allylic substitution (i.e., Tsuji–Trost reaction) using N-heterocyclic carbene as a ligand was investigated. It has been proven that an imidazolium salt 2d having bulky aromatic rings attached to the nitrogens in its imidazol-2-ylidene skeleton is suitable as a ligand precursor and that a Pd2dba3–imidazolium salt 2d–Cs2CO3 system is highly efficient for producing a Pd–NHC catalyst in this reaction. Allylic substitution using a Pd–NHC complex differed from that using a Pd–phosphine complex as follows: (1) the reaction using a Pd–NHC complex required elevated temperature (50 °C or reflux in THF), (2) allylic carbonates were inert to a Pd–NHC complex, and (3) nitrogen nucleophiles such as sulfonamide and amine did not react with allylic acetate. It was also found that allylic substitution with a soft nucleophile using a Pd–NHC catalyst proceeds via overall retention of configuration to give the product in a stereospecific manner, the stereochemical reaction course obviously being the same as that of the reaction using a Pd–phosphine complex.

Graphical abstractA Pd(0)-catalyzed allylic substitution (i.e., Tsuji–Trost reaction) of various allylic acetates, lactone, and carbonate using N-heterocyclic carbene as a ligand was investigated. Allylic substitution using a Pd–NHC complex differed from that using a Pd–phosphine complex as follows: (1) the reaction using a Pd–NHC complex required elevated temperature (50 °C or reflux in THF), (2) allylic carbonates were inert to a Pd–NHC complex, and (3) nitrogen nucleophiles such as sulfonamide and amine did not react with allylic acetate. It was also found that allylic substitution with a soft nucleophile using a Pd–NHC catalyst proceeds via overall retention of configuration to give the product in a stereospecific manner, the stereochemical reaction course obviously being the same as that of the reaction using a Pd–phosphine complex.Figure optionsDownload full-size imageDownload as PowerPoint slide