Sonogashira coupling template

Pd and Cu catalytic cycles of the Sonogashira coupling: oxidative addition of R¹–X, transmetalation from the copper acetylide and reductive elimination of R¹–C≡C–R²; CuX plus amine base turns the terminal alkyne into Cu–C≡CR²; key step: the amine deprotonates the alkyne.

What the template shows

• A Pd cycle and a Cu cycle: the copper acetylide carries the alkyne to palladium
• Overall: R¹–X + H–C≡C–R² → R¹–C≡C–R² (cat. Pd(0)L₂, cat. CuI, Et₃N)
• Transmetalation (Pd cycle, step 2)
• C≡C–R² moves from Cu to Pd
• and CuX is released
• π-Coordination of the alkyne to Cu(I) makes its C–H acidic enough for the amine; the acetylide joins the Pd cycle at transmetalation (step 2) and CuX is released.
• Two cycles: Pd does the oxidative addition and the C–C bond formation; Cu(I) activates the alkyne.
• The amine (Et₃N, iPr₂NH) is the base and often the solvent.
• Copper-free versions avoid Glaser homocoupling of the alkyne (R²C≡C–C≡CR²), a side reaction promoted by Cu and O₂.
• Works for aryl and vinyl halides; reactivity I > Br ≫ Cl.
• Key step: the amine deprotonates the alkyne
• Shown without copper for clarity: the N lone pair takes the alkyne proton and the C–H electrons stay on carbon as the acetylide, which copper captures as Cu–C≡CR².
• terminal alkyne
• L = phosphine (e.g. PPh₃); ligands are named in the captions, not drawn · every part of this figure is editable

Drawn with 36 atoms, 7 arrows, 83 shapes – every one editable in MolDraw.

Sources

• Chinchilla & Nájera, Chem. Rev. 2007, 107, 874 Review
• Hartwig, Organotransition Metal Chemistry: From Bonding to Catalysis, University Science Books 2010 Textbook