M.C. White. Chem 153 Cross-Coupling-94- Week of octo ber 1. 2002 Stille: Ligand Effects Pd,dba3 Ligand Relative Pd: L THF. 50%C 12145 It has been observed experimentally that increasing the concentration of (2-furyl)3P 1:2 ND 20 monodentate phosphine ligands decreases the rate of the Stille reaction No correlation exists between cone angles(0)and observed rates indicating that the ligand effect is not of steric origin. The ligand effect is thought to AsPh3 1: 2 be electronic in nature where phosphines that are poor o-donors promote the cross-coupling more effectively than those that are strong o-donors Farina JACS 1991(113)9585 Kinetics studies support a mechanism Relative involving fast oxidative addition followed igand k1/k1 by a rate-determining transmetalation event which requires initial solvent/ligand X exchange. This predissociation event is disfavored thermodynamically with strong (2-furyl)P 6x10-3 donor ligands such as pph and more favored with weak donor ligands such as AsPh3 0.86 1100 AsPh3 SI I Pd2dba)3, L(1: 4 50°C.THF The existence of this pre-equilibrium in the transmetalation mechanism is a subject of much debate in the literature. An alternative proposal involves a tin-mediated associative substitution where transmetalation occurs via a pentacoordinate Pd intermediate. Espinet JACS 2000 (122)117 I and Espinet JACS1998(120)8978
M.C. White, Chem 153 Cross-Coupling -94- Week of October 1, 2002 Stille: Ligand Effects Pd2dba3 + Ligand Bu3Sn Ligand Pd:L Relative rate PPh3 (2-furyl)3P AsPh3 It has been observed experimentally that increasing the concentration of monodentate phosphine ligands decreases the rate of the Stille reaction. No correlation exists between cone angles (θ) and observed rates indicating that the ligand effect is not of steric origin. The ligand effect is thought to be electronic in nature where phosphines that are poor σ-donors promote the cross-coupling more effectively than those that are strong σ-donors. θ 145o ND 142o 1:2 1:2 1:2 1 20 78 I THF, 50oC Farina JACS 1991 (113) 9585. Pd L L I Pd [S] L I k1 Bu3Sn + L + Bu3SnI 1 2 I Pd2(dba)3,L (1:4) 50oC, THF k-1 k2 The existence of this pre-equilibrium in the transmetalation mechanism is a subject of much debate in the literature. An alternative proposal involves a tin-mediated associative substitution where transmetalation occurs via a pentacoordinate Pd intermediate. Espinet JACS 2000 (122) 11771 and Espinet JACS 1998 (120) 8978. Ligand k1/k-1 PPh3 (2-furyl)3P AsPh3 Relative kobs 1 105 1100 <5 x 10-5 6 x 10 -3 0.86 Kinetics studies support a mechanism involving fast oxidative addition followed by a rate-determining transmetalation event which requires initial solvent/ligand exchange. This predissociation event is disfavored thermodynamically with strong donor ligands such as PPh3, and more favored with weak donor ligands such as AsPh3
M C. White/M. w. Kanan Chem 153 Cross-Coupling-95- Week of octo ber 1. 2002 Stille: Mechanism of pa/Sn Transmetalation open 2(cyclic) SE2 (cyclic, pentacoordinate) S旷R R RPd……C…SnR X…pdR X…PdR R favored in highly polar favored in non-polar solvents and/or nucleophilic solvents Farina Pure Appl Chem. 1996 68: I pp 73-78 The mechanism for Pd/Sn transmetalation is highly dependent on reaction conditions, and the subject of ongoing debate in the literature Stille jacs1983105669-670,6129613 Epsinet JAcs19981208978-8985,20002211771-11782
M.C. White/M.W. Kanan Chem 153 Cross-Coupling -95- Week of October 1, 2002 Stille: Mechanism of Pd/Sn Transmetalation The mechanism for Pd/Sn transmetalation is highly dependent on reaction conditions, and the subject of ongoing debate in the literature. Stille JACS 1983 105 669-670, 6129-6137. Epsinet JACS 1998 120 8978-8985, 2000 122 11771-11782. Pd C H H R' R SnR3 Cl Sn R' X Pd R L L δ+ δ+ δ− L SE2 (open) SE2 (cyclic, pentacoordinate) Sn R' X Pd R SE2 (cyclic) L favored in highly polar and/or nucleophilic solvents favored in non-polar solvents Farina Pure & Appl. Chem. 1996 68:1 pp 73-78