Merck

Cross-Coupling

A cross-coupling reaction in organic synthesis occurs when two fragments are joined together with the aid of a metal catalyst. Cross-coupling has been an essential reaction in catalytic chemistry for the past 30 years starting with the pioneering work by Heck, Negishi, and Suzuki, who were awarded the Nobel Prize in Chemistry in 2010 for palladium-catalyzed cross-coupling. As one of the most versatile and powerful bond-forming methods in synthetic organic chemistry, the field of cross-coupling has matured to the point where nearly any two fragments can be coupled with the right catalyst. With its usage increasing exponentially, the field has grown to include numerous strategies for carbon-carbon, carbon-nitrogen, and carbon-oxygen bond formation, including key reactions such as:

  • Buchwald-Hartwig amination, the cross-coupling of an aryl (pseudo)halide and an amine, is a staple reaction for chemists across a wide range of disciplines.
  • Heck coupling is the cross coupling of an unsaturated halide with an alkene to give substituted alkenes.
  • Negishi coupling is the cross-coupling of an aryl (pseudo)halide and an organozinc nucleophile to form C-C bonds.
  • Sonogashira coupling is the cross-coupling of an aryl (pseudo) halide with a terminal alkyne to give disubstituted acetylenes.
  • Stille coupling, the cross-coupling of an aryl (pseudo)halide and stannane, is a functional reaction for carbon-carbon bond formation with few limitations on the R-groups.
  • Suzuki-Miyaura coupling, the cross-coupling of an aryl (pseudo)halide and organoborate, is a versatile reaction for carbon-carbon bond formation.



Related Technical Articles

  • G3 and G4 Buchwald palladium precatalysts are the newest air, moisture, and thermally stable crossing-coupling complexes used in bond formation for their versatility and high reactivity.
  • MIDA-protected boronate esters are easily handled, indefinitely bench-top stable under air, compatible with chromatography, and unreactive under standard anhydrous cross-coupling conditions, even at temperatures up to 80 °C.
  • Lipshutz and co-workers have recently developed a second generation technology to their original PTS-enabling surfactant based on the polyoxyethanyl-α-tocopheryl succinate derivative, TPGS-750-M.
  • C2-symmetric chiral bisoxazolines (BOX) are privileged structures because they promote a great number of transformations with unprecedented selectivity.1
  • The Pd-catalyzed C–N bond formation has become an important synthetic reaction in the past 20 years. Several research groups have investigated this reaction and developed very versatile catalysts. Buchwald and coworkers have been very active in synthesizing and developing a portfolio of phosphine ligands for this transformation and other cross-coupling reactions.
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