The Problem with Problems: Fundamental to Applied Research Using Palladium

Abstract

This Account describes the development of our cross-coupling and medicinal chemistry research from its origins at the outset of my independent career through to the present day. Throughout, the decisions and motivations as well as the mistakes and pitfalls are discussed.1 Introduction2 Hobbies and Interests3 Scooped before Starting4 Opportunity from Collaboration5 Chemoselective Suzuki–Miyaura Cross-Coupling6 Applications to the Medicinal Chemistry Campaign7 Autotaxin and Heterocycle Synthesis8 ATX Hybrids and Pd(II) Speciation9 Conclusions

Direct Chan–Lam Amination and Etherification of Aryl BMIDA Reagents

“…We have been interested in the use of arylboronic acid Nmethyliminodiacetic acid esters (ArBMIDA) as components within selective cross-coupling processes. [17][18][19][20][21][22][23][24][25][26][27][28][29][30] Despite their widely appreciated utility in chemoselective synthesis, only one example of a Chan-Lam reaction using ArBMIDA has been disclosed, with no yield given. [31] Here, we report the development of a general approach for Chan-Lam amination and etherification of ArBMIDA.…”

“…We have been interested in the use of arylboronic acid N ‐methyliminodiacetic acid esters (ArBMIDA) as components within selective cross‐coupling processes [17–30] . Despite their widely appreciated utility in chemoselective synthesis, only one example of a Chan–Lam reaction using ArBMIDA has been disclosed, with no yield given [31] …”

Palladium-catalyzed Suzuki–Miyaura cross-coupling with α-aminophosphonates based on 1,3,4-oxadiazole as ligands

“…of a base [1]. Since this discovery, the Suzuki-Miyaura cross-coupling reaction has become the preferred method for preparing biaryls by Csp 2 -Csp 2 bond formation, with extensive applications in the synthesis of a wide range of natural products, pharmaceuticals, polymers, and advanced materials [2][3][4][5][6][7][8][9][10]. Initially, tetrakis(triphenylphosphine)palladium(0) was employed as catalyst [11], and since then, much effort has been made to develop more efficient catalytic systems able to accelerate the rate of the crosscoupling and/or substitute brominated derivatives with less reactive compounds such as their chlorinated equivalents or acyl electrophiles [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26].…”