Cross-coupling reactions

This lecture serves as an introduction to the world of cross-coupling reactions. It offers insights into the historical evolution of this research domain and acquaints you with the key cross-coupling reactions that will be explored throughout this series of lectures. The main topics covered in the lecture are: definition of cross-coupling reactions; overview of the mechanism of cross-couplings; popularity of cross-couplings in medicinal chemistry and related disciplines; the Nobel Prize in Chemistry 2010; the main periods of the development of cross-coupling chemistry; cross-couplings mediated by transition metals; the first catalytic and selective cross-couplings; the discovery of palladium (Pd) and the first catalysts on it; Heck coupling - the first Pd-catalyzed cross-coupling; Sonogashira coupling; introduction of less reactive organometallics; Negishi coupling; introduction of stable organometallics; Stille coupling; Suzuki-Miyaura coupling; what makes the Suzuki-Miyaura coupling special?; Hiyama coupling; Buchwald-Hartwig amination; overview of phosphines, their stability and properties; configurational stability of phosphines and P-chiral ligands; determination and quantification of stereoelectronic properties of phosphines; first observations of the ligand effect on the efficiency of cross-couplings; sensitivity of Buchwald-Hartwig amination towards used ligands; ligand control the β-hydride elimination; the effect of bulky, σ-donor ligands on the activity of Pd-catalysts; the importance of monoligated catalytic species in the catalytic cycle of cross-couplings; the effect of ligand substituents on the elementary steps of cross-couplings; the rise of Buchwald's ligands; different generations of Buchwald's ligands; the effect of substituents on the activity of Buchwald's ligands; the rise of Hartwig's ligands; triadamantylphosphine; ylide-substituted phosphines; the discovery of NHCs and classification of NHC ligands; NHCs in nature; comparison of NHC ligands and phosphines in homogeneous catalysis; σ-donor properties and π-accepting abilities of NHC ligands; back-bonding in metal-complexes of NHC ligands; quantification of the electronic properties of NHCs; quantification of the steric hindrance in NHCs; percent buried volume and steric maps; the most popular NHC ligands; tuning the stereoelectronic properties of NHC ligands; cross-couplings with NHC-Pd catalysts; NHC-based precatalysts; Organ's NHC ligands and precatalysts; common routes for activation of precatalysts; advantages of the use of preformed catalysts; the first generation of preformed catalysts; modern preformed catalysts of the type L2Pd(0); modern preformed catalysts of the type L2Pd(II); Buchwald's precatalysts; Colacot's precatalysts; precatalysts based on NHC ligands; precatalysts based on Ni; examples of highly efficient cross-couplings of unreactive substrates enabled by preformed catalysts; factors controlling the reactivity of aryl halides and pseudohalides; reactivity of pseudohalides based on phenols; reactivity of pseudohalides from anilines; C-C bond activation in cross-couplings; the ranking of reactivity in aryl halides and pseudohalides; factors controlling the reactivity of organometallics; how can we effect on the reactivity of aryl halides, pseudohalides, and organometallic compounds; rational design of the cross-couplings and retrosynthesis; anisoles as coupling partners in cross-couplings; esters as coupling partners in cross-couplings; nitro compounds as coupling partners in cross-couplings; the origins of site-selectivity in polyhalogenated systems; chemoselective cross-couplings; regioselective cross-couplings; electronic control of regioselectivity in cross-couplings; prediction of regioselectivity controlled by electronics; steric control of regioselectivity in cross-couplings; regioselectivity control by a directing group; ligand control of regioselectivity in cross-couplings; regioselectivity control by solvent or additive; chemoselective cross-couplings enable by the protecting groups in organometallics; polyfunctionalization of organic molecules enabled by cross-couplings; total synthesis of (+)-Linoxepin by Catellani reaction; synthesis of cyclic peptides by Suzuki-Miyaura reaction; synthesis of cyclic peptides by Stille coupling; synthesis of alkaloids by Buchwald-Hartwig amination; synthesis of fungicides by Sonogashira coupling and Suzuki-Miyaura reaction; synthesis of insecticides by Buchwald-Hartwig amination; synthesis of antibiotics by Buchwald-Hartwig amination; synthesis of anti-inflammatory drugs by Suzuki-Miyaura reaction; synthesis of pharmaceuticals for the treatment of asthma by Heck reaction; production of self-repairable polymers by Buchwald-Hartwig amination; production of organic semiconductors by Sonogashira coupling and Buchwald-Hartwig amination; production of organic fluorescent dyes by Buchwald-Hartwig amination. The cover picture is adapted from stock image library of Office 365.