Stille Coupling oe ests Pd(0) or The Stille cross—coupling is the palladium catalyzed reaction between stannanes and halides to generate a C-C bond. halides x x fF fx Cr a* Alkynyl Alkenyl hy Allyl Mechanism x Pd(0)Ln Cw Oxidative Reductive Addition Elimination Phy xoPallLn hy el Pally ee Retr LL Ph ‘ Ph Transmetalation wh, SE, X-Sn'Bu3 1. Oxidative addition of an organic halide to Pd(0) to form Pd(Il). 2. Transmetalation between Pd(Il) and the organotin reagent. 3. Reductive elimination to form the C-C sigma bond and regeneration of the catalyst. @LluisLlorens CS)Kumada Coupling RigX pal ax or Se R-LI Solvent / Ligand The Kumada Cross—coupling is the transition metal-catalyzed carbon-carbon bond forming reaction of alkenyl or aryl halides and organomagnesium or organolithium reagents. Mechanism Pd catalyzed LnPd®) oxidative addition l=] elimination UZ Xo Ppa _ Cee C encaniis 1. Initially, the electron-rich Pd(0) catalyst inserts into the R-X bond of the organic halide. This oxidative addition forms an organo-Pd(II}-complex. 2. Subsequent transmetalation with the Grignard or the organolithium reagent forms a hetero-organometallic complex. 3. Before the next step, isomerization is necessary to bring the organic ligands next to each other into cis positions. 4. Finally, reductive elimination leads to the formation of a C-C bond and releases the cross coupled product while regenerating the Pd(0) catalyst. Ni-catalyzed LNIO% oy 2R-MgX 2. XMgX : ~S XMgX Ri Revi, Ni Ly R-X “ eosinaton_ @lluisLlorensHeck Coupling Pd(0) Be SR CS Ligand, base The Heck Reaction is the cross—coupling between an unsaturated halide or triflate and an alkene in the presence of a base and a palladium catalyst. Mechanism Q a HY Br Br Pit sid 2 Pd(O)L, C — Ae: (OLn Oxidative ecoordination pf era Addition Elimination Jf Pata B-hydride elimination 4, H~scoome ee complex ft formation Migratory Es insertion 1. Oxidative addition of an organic halide to Pd(0) to form Pail). 2. Pd forms a TT complex with the alkene. 3. Migratory insertion: the alkene inserts in the Pd—C bond in a syn addition step. 3. B-hydride elimination leads to the m complex. 4. Decoordination of the complex followed by reductive elimination to regenerate the catalyst. 8 oer . AY CooEt erat rr Br Syn elimination Yo Ph Yoet Woooet Dat Hace Br @luisLlorensé ) Named Reactions in Organic Chemistry ao Negishi Coupling X 2.Znx Pd oR ar Um or Ni RSonogashira Coupling Pd(0) BZ oto Cul, ccalan The Sonogashira cross—coupling is the copper-palladium catalyzed reaction of terminal alkynes with aryl or vinyl halides. Mechanism Pd(O)L2 ( Oxidative Addition Reductive Elimination Ph, wm yPatiNLe Transmetalation SSE Et)NH*X: Ae a 1. Oxidative addition of an organic halide to Pd(0) to form Pd(I!). 2. Deprotonation of the alkyne and formation of copper acetylide. 3. Transmetalation between Pd(Il) and the acetylide. 4. Reductive elimination to form the C-C sigma bond and regeneration of the catalyst. @LluisLlorens