Cross‐Coupling Reactions to sp Carbon Atoms

Designing Homogeneous Copper-Free Sonogashira Reaction through a Prism of Pd–Pd Transmetalation

“…As reported by Sonogashira et al, alkynylation in the presence of copper salts proceeds under much milder conditions. ,, Copper additives, however, promote Glaser–Hay competitive homocoupling of alkyne and interfere with some functional groups potentially present in the coupling partners like azide, amine, and alkyne. During the isolation process, removal of copper cocatalyst may complicate the workup and purification, especially in the synthesis of APIs. , When it comes to a bulk industrial process, recovery of the precious metal from spent catalysts is more challenging for the copper cocatalyzed than the copper-free process. , Although homogeneous copper-free alkynylation has witnessed tremendous improvements, it mostly benefited from development of novel ligands ,,, and technologies. Aqueous micellar catalysis developed by the groups of Lipshutz, and Sparr and Parmentier is a notable example of the latter.…”

“…This is exemplified by the synthesis of many Food and Drug Administration (FDA) approved active pharmaceutical ingredients (APIs), , including Terbinafine (Sandoz, squalene epoxide inhibitor), Ponatinib (Ariad Pharmaceuticals, tyrosine-kinase inhibitor), Tazarotene (Allergan, receptor-selective retinoid), and Eniluracil (GlaxoSmithKline, dihydropyrimidine dehydrogenase inactivator) . As reported by Sonogashira et al, alkynylation in the presence of copper salts proceeds under much milder conditions. ,, Copper additives, however, promote Glaser–Hay competitive homocoupling of alkyne and interfere with some functional groups potentially present in the coupling partners like azide, amine, and alkyne. During the isolation process, removal of copper cocatalyst may complicate the workup and purification, especially in the synthesis of APIs. , When it comes to a bulk industrial process, recovery of the precious metal from spent catalysts is more challenging for the copper cocatalyzed than the copper-free process. , Although homogeneous copper-free alkynylation has witnessed tremendous improvements, it mostly benefited from development of novel ligands ,,, and technologies.…”

“…Although the palladium catalyzed C–C bond formation between aryl or vinyl halides and terminal alkynes by Heck and Cassar evolved into the most effective tool for the synthesis of disubstituted alkynes, it is the copper cocatalyzed variant that has mostly entered industrial applications (Scheme ). , …”

Synthesis and chemosensing properties of cinnoline-containing poly(arylene ethynylene)s

“…Triazenes 3a,b were synthesized from 4-bromo-2-iodophenyltriazene 1 by the Sonogashira coupling [ 44 – 45 ] with hexyne ( 2a ) and TMS-protected diacetylene 2b using conditions for the one-pot TMS group removal and the Sonogashira coupling developed recently [ 46 ]. The last reaction could also be defined as a type of sila -Sonogashira coupling [ 47 – 48 ], which is an extremely convenient method for the one-step synthesis of non-symmetrically substituted diarylacetylenes [ 49 – 50 ]. Mild conditions allowed carrying out both reactions chemoselectively leaving the bromine atom for further synthetic steps.…”

Decarboxylative and dehydrative coupling of dienoic acids and pentadienyl alcohols to form 1,3,6,8-tetraenes

“…Cross-coupling reactions provide avenues to these otherwise difficult reactions, but often require prefunctionalization of the coupling partners [ 1 – 9 ]. However, recent C–H activation research has enabled the use of further simplified starting materials [ 10 – 18 ]. Another approach to the formation of C–C bonds is through decarboxylative coupling reactions ( Scheme 1 ).…”