Palladium-catalyzed substitution of (coumarinyl)methyl acetates with C-, N-, and S-nucleophiles

Abstract

SummaryThe palladium-catalyzed nucleophilic substitution of (coumarinyl)methyl acetates is described. The reaction proceeds though a palladium π-benzyl-like complex and allows for many different types of C-, N-, and S-nucleophiles to be regioselectively added to the biologically active coumarin motif. This new method was utilized to prepare a 128-membered library of aminated coumarins for biological screening.

Palladium-catalyzed, pyrrolidine-mediated arylmethylation of ketones and aldehydes with coumarinyl(methyl) acetates

“…We have recently shown that palladium catalyzes the amination of (coumarinyl)methyl acetates with various amines, including pyrrolidine. 19 Thus, it was somewhat surprising that the benzyl amine product resulting from nucleophilic attack of the amine on the intermediate Pd-π-benzyl complex was never observed (eqn ( 6)). This suggests that enamine formation is faster than ionization of the (coumarinyl)methyl acetate moiety.…”