Addressing the Challenges in Suzuki–Miyaura Cross-Couplings by Ligand Design

Abstract

Despite the increasing applicability of cross-couplings in organic synthesis, there remain many challenging issues. In the past years, we have designed and developed several classes of conformationally well-defined monophosphorus ligands: (1) bulky biaryl monophosphorus ligands such as BI-DIME and AntPhos; (2) bulky monophosphorus ligands with a second coordination site such as P,P=O ligands; (3) P-chiral monophosphorus ligands. These phosphorus ligands have enabled efficient sterically hindered aryl-aryl and aryl-alkyl cross-couplings, sterically hindered aryl-isopropyl cross-couplings, and asymmetric ary-aryl cross-couplings. The high reactivity, chemoselectivity, and enantioselectivity achieved in these reactions have allowed practical applications in total synthesis of natural products and drug molecules, leading to an efficient synthesis of a key gossypol intermediate, and, for the first time, asymmetric catalytic synthesis of korupensamine A, korupensamine B, and michellamine B. 1 Introduction 2 Sterically Hindered Aryl–Aryl Cross-Couplings 3 Sterically Hindered Aryl–Alkyl Cross-Couplings 4 Asymmetric Suzuki-Miyaura Cross-Couplings 5 Applications in the Syntheses of Natural Products and Drug Molecules 6 Conclusions