Solid-phase synthesis of peptide based phosphine ligands:towards combinatorial libraries of highly selective peptido-phosphine transition metal catalysts

摘要

In Nature enzymes achieve their excellent efficiency and selectivity in the catalysis of biological processes through a combination of binding affinity and delicate catalytic machinery.Hence,it is obvious to mimic Nature by designing peptidic catalysts for asymmetric synthesis.However,high catalyst selectivity calls for the development of a method for the identification of the most efficient catalyst for any specific reaction.The solution could be high-throughput screening of combinatorial libraries of potential catalysts,thereby,for each new reaction/synthetic challenge,being able to rapidly pick the best catalyst.Immobilization of library members on individual beads would greatly facilitate this screening.Here new methodology for the solid-phase synthesis of peptide based phosphine ligands and their use in asymmetric palladium catalyzed allylic substitution is presented.The methodology should be perfectly suited for the generation of resin bound catalyst libraries using standard split and pool combinatorial peptide synthesis.