Mechanism of the Stille Reaction. 1. The Transmetalation Step. Coupling of R1I and R2SnBu3 Catalyzed by trans-[PdR1IL2] (R1 = C6Cl2F3; R2 = Vinyl, 4-Methoxyphenyl; L = AsPh3)

The so far accepted mechanism of the Stille reaction (palladium-catalyzed cross-coupling of organotin reagents with organic electrophiles) is criticized. Based on kinetic studies on catalytic reactions, and on reactions with isolated intermediates, a corrected mechanism is proposed. The couplings between R 1 I ( 1 ) (R 1 = C 6 Cl 2 F 3 = 3,5-dichlorotrifluorophenyl) and R 2 SnBu 3 (R 2 = CH CH 2, 2a; C 6 H 4 -4-OCH 3, 2b ), catalyzed by trans -[PdR 1 I(AsPh 3 ) 2 ] ( 3a ), give R 1 −R 2 and obey a first-order law, r obs = a [ 3a ][ 2a ]/( b + [AsPh 3 ]), with a = (2.31 ± 0.09) × 10 - 5 s - 1 and b = (6.9 ± 0.3) × 10 - 4 mol L - 1, for [ 1 ] = [ 2a ] = 0−0.2 mol L - 1, [ 3a ] = 0−0.02 mol L - 1, and [AsPh 3 ] = 0−0.07 mol L - 1, at 322.6 K in THF. The only organopalladium(II) intermediate detected under catalytic conditions is 3a . The apparent activation parameters found for the coupling of 1 with 2a support an associative transmetalation step (Δ H ⧧ obs = 50 ± 2 kJ mol - 1, Δ S ⧧ obs = −155 ± 7 J K - 1 mol - 1 in THF; and Δ H ⧧ obs = 70.0 ± 1.7 kJ mol - 1, Δ S ⧧ obs = −104 ± 6 J K - 1 mol - 1 in chlorobenzene, with [ 1 ] 0 = [ 2 ] 0 = 0.2 mol L - 1, [ 3a ] = 0.01 mol L - 1 ). The reactions of 2a with isolated trans -[PdR 1 X(AsPh 3 ) 2 ] (X = halide) show rates Cl > Br > I. From these observations, the following mechanism is proposed: Oxidative addition of R 1 X to PdL n gives cis -[PdR 1 XL 2 ], which isomerizes rapidly to trans -[PdR 1 XL 2 ]. This trans complex reacts with the organotin compound following a S E 2 (cyclic) mechanism, with release of AsPh 3 (which explains the retarding effect of the addition of L), to give a bridged intermediate [PdR 1 L(μ-X)(μ-R 2 )SnBu 3 ]. In other words, an L-for-R 2 substitution on the palladium leads R 2 and R 1 to mutually cis positions. From there the elimination of XSnBu 3 yields a three-coordinate species cis -[PdR 1 R 2 L], which readily gives the coupling product R 1 −R 2 .