M.C. White. Chem 153 Cross-Coupling- 120- Week of octo ber 8. 2002 Sonogashira: in situ, metal assisted deprotonation Cul(10 mol%), Et] NH solvent 3h nogashira TL 1975 (50) 100% stereospecificity catalytic cycle Order of reactivity of Csp-X component NHX Mild aryl bromide sonogashi P(t-Bu Pa(CHCN)Cl2(3%) R' Cu(39%) note: can also start with a pd(o) NEt3 (1.2 eq) source(e.g. Pd(Ph3 P) R=COMe, H, Me R'=Ph, hexyl, dioxane,rt OMe. NMe, C(OH(CH3)70-90% d RXR=aryl, alkeny =L. Br. otf Cl reductive P(t-Bu)3 is uniquely effective under these conditions. All other phosphines screened(PPh3, P(o-tol)3, dppf, PCy3)gave less Buchwald Fu OL 2000(2)1729 Php (PhaP),Pd Compare pKa's EtnA The acidity of the acetylene hydrogen is enhanced via T-complexation CuX R2NH'X nogashira JOMC 2002 (653)46M.C. White, Chem 153 Cross-Coupling -120- Week of October 8, 2002 Sonogashira: in situ, metal assisted deprotonation Cl PdII Ph3P Cl PPh3 Ph H Br + (5 mol%) CuI (10 mol%), Et2NH solvent rt, 3h The first report: Ph 90% yield Sonogashira TL 1975 (50) 4467. 100% stereospecificity p Ka = 23 Cl PdII Ph3P Cl PPh3 catalytic cycle: ICu R CuX H R R3NH+ X￾PdII PPh3 PPh3 R R transmetalation (PPh3)2Pd0 note: can also start with a Pd(0) source (e.g. Pd(Ph3P)4). R' PdII Ph3P X PPh3 R R R' X R' = aryl, alkenyl X = I, Br, OTf, Cl CuX ICu R H R R3NH+ X- (Ph3P)nPdII R' R transmetalation oxidative addition reductive elimination R R' Ph H Et3NH+ p Ka = 10.75 Compare pKa's: The acidity of the acetylene hydrogen is enhanced via π-complexation : R H CuI Order of reactivity of Csp2-X component: I , Br > I > Cl >> Br Mild aryl bromide Sonogashira couplings with P(t-Bu)3 Br R R= COMe, H, Me OMe, NMe2 R' R' = Ph, hexyl, C(OH)(CH3)2 R' R CuI (3%) NEt3 (1.2 eq) dioxane, rt Pd(CH3CN)2Cl2 (3%) P(t-Bu)3 (6%) 70-90% P(t-Bu)3 is uniquely effective under these conditions. All other phosphines screened (PPh3, P(o-tol)3, dppf, PCy3) gave less than 2% yield. Buchwald & Fu OL 2000 (2) 1729. Sonogashira JOMC 2002 (653) 46