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

Abstract

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 R1I (1) (R1 = C6Cl2F3 = 3,5-dichlorotrifluorophenyl) and R2SnBu3 (R2 = CHCH2, 2a; C6H4-4-OCH3, 2b), catalyzed by trans-[PdR1I(AsPh3)2] (3a), give R1−R2 and obey a first-order law, robs = a[3a][2a]/(b + [AsPh3]), 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 [AsPh3] = 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 (ΔH⧧obs = 50 ± 2 kJ mol-1, ΔS⧧obs = −155 ± 7 J K-1 mol-1 in THF; and ΔH⧧obs = 70.0 ± 1.7 kJ mol-1, ΔS⧧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-[PdR1X(AsPh3)2] (X = halide) show rates Cl > Br > I. From these observations, the following mechanism is proposed: Oxidative addition of R1X to PdLn gives cis-[PdR1XL2], which isomerizes rapidly to trans-[PdR1XL2]. This trans complex reacts with the organotin compound following a SE2(cyclic) mechanism, with release of AsPh3 (which explains the retarding effect of the addition of L), to give a bridged intermediate [PdR1L(μ-X)(μ-R2)SnBu3]. In other words, an L-for-R2 substitution on the palladium leads R2 and R1 to mutually cis positions. From there the elimination of XSnBu3 yields a three-coordinate species cis-[PdR1R2L], which readily gives the coupling product R1−R2.