The mechanism of palladium(II)-mediated C-H cleavage with mono-N-protected amino acid (MPAA) ligands: Origins of rate acceleration

Abstract

It has long been known that transition metals are capable of interacting with, cleaving, and mediating the functionalization of activated and unactivated carbon-hydrogen (C-H) bonds. Broadly speaking, a basic underlying principle in the fields of inorganic and organometallic chemistry is that the primary and secondary coordination spheres around a metal affect its reactivity and selectivity in elementary reactions. Hence, ligand design in transition metal catalysis has been a captivating area of research for over half a century. The discovery and development of novel ligands to promote and control otherwise recalcitrant C-H functionalization reactions is now at the forefront of organic and organometallic chemistry. Central to this line of inquiry is the interplay between ligand, substrate, metal, and reaction mechanism. This Review highlights the mechanistic details of palladium(II)-mediated C-H cleavage with mono-N-protected amino acid (MPAA) ligands. Relevant historical background is discussed, the key discoveries in catalysis with MPAAs are examined, experimental and computational studies to elucidate reaction mechanisms are presented, and possible future directions are described.