Cross-Coupling

A cross-coupling reaction in organic synthesis occurs when two molecular fragments are joined together with the assistance of a metal catalyst. This type of reaction has been a cornerstone in catalytic chemistry for the past three decades, beginning with the pioneering work of Heck, Negishi, and Suzuki, who were awarded the Nobel Prize in Chemistry in 2010 for their contributions to palladium-catalyzed cross-coupling. As one of the most versatile and powerful methods for bond formation in synthetic organic chemistry, cross-coupling has evolved to a point where nearly any two fragments can be coupled using the appropriate catalyst. With its rapid growth, the field now includes various strategies for forming carbon-carbon, carbon-nitrogen, and carbon-oxygen bonds. Notable reactions in this category include: 1) Buchwald-Hartwig amination, which involves the cross-coupling of an aryl (pseudo)halide with an amine and is widely used in many chemical disciplines; 2) Heck coupling, where an unsaturated halide reacts with an alkene to produce substituted alkenes; 3) Negishi coupling, which couples an aryl (pseudo)halide with an organozinc nucleophile to form carbon-carbon bonds; 4) Sonogashira coupling, the cross-coupling of an aryl (pseudo)halide with a terminal alkyne to form disubstituted acetylenes; 5) Stille coupling, which involves the cross-coupling of an aryl (pseudo)halide with stannane for carbon-carbon bond formation, with few limitations on substituent groups; and 6) Suzuki-Miyaura coupling, a versatile reaction for carbon-carbon bond formation between an aryl (pseudo)halide and an organoborate. These reactions have greatly advanced the ability to construct complex organic molecules efficiently.