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)

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 R, 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 (∆H q obs ) 50 ( 2 kJ mol -1 , ∆S q obs ) -155 ( 7 J K -1 mol -1 in THF; and ∆H q obs ) 70.0 ( 1.7 kJ mol -1 , ∆S q obs ) -104 (). 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 .

The Mechanisms of the Stille Reaction

“…[35] The need to explain the different stereochemical outcome of the reactions in Scheme 29 and consideration of quantitative results on transmetalation rates led to the proposal by Espinet and Casado of a dual catalytic cycle with two different transition states, one cyclic and one open, 38 and 39, respectively (Scheme 30). [96,188] The upper cycle in Scheme 30 depicts the cyclic transmetalation as an associative process assisted by the formation of a PdÀXÀSn second bridge. This mechanism leads to the exchange of L (and not X) for R 2 , forces retention (and not inversion) of the configuration at C a , and leads to a cis (rather than a trans) [PdR 1 R 2 L 2 ] complex, from which coupling is immediate.…”

“…[176] It is difficult to ascertain which species undergoes faster transmetalation even by kinetic studies, because the kinetic equations show similar dependences on the concentration of the reagents. Whereas in some cases it seems clear that the associative transmetalation occurs on the dominant [PdR 1 XL 2 ] complex, [188] Amatore, Jutand, and coworkers showed in a nice study that in certain other cases the reaction mainly proceeds by associative substitution on the solvento complex [PdR 1 XL(S)] ((S) trans to L), even when the concentration of this solvento complex is kept very low through the addition of L. [189] However, a substitution of (S) for R 2 (as in the modern Scheme 30) rather than of X for R 2 (as in Schemes 2 and 28) is still proposed. Thus, Scheme 30 is fairly comprehensive, and most experimental observations, including the stereochemical outcome of the transmetalation can be rationalized satisfactorily within this framework (retention of configuration implies a cyclic pathway, inversion an open pathway).…”

Mechanistic Aspects of Metal‐Catalyzed C—C and C—X Bond‐Forming Reactions

“…The observed dependence on the ligand concentration has recently been explained by Espinet within the framework of an associative mechanism (Scheme 1-26) [147,148]. These studies were based on kinetic measurements of the palla- [50,149].…”

“…The rate-determining step in the coupling of aryl halides or triflates with aryl-or alkenyl stannanes can be either the transmetallation or the oxidative addition, depending on the exact circumstances of the reaction [147,150]. On the other hand, in the coupling of allylic electrophiles, the reductive elimination step might become rate-determining.…”

Nicht ganz unbeteiligt: der Einfluss von Olefinen auf übergangsmetallkatalysierte Kreuzkupplungen

“…Zahlreiche ausführliche Kinetikstudien ermöglichten Einblicke in spezifische Mechanismen. [18] Doch konnte keine auf alle Situationen anwendbare Theorie entwickelt werden, sondern es wurden mehrere Einzelmechanismen formuliert. Während die relative Transmetallierungsgeschwindigkeit von Substituenten über Hybridisierung [19] und elektronischen Charakter [20] verstanden ist, wurden nur wenige quantitative Untersuchungen zum Einfluss des elektronischen Charakters des Metallzentrums auf die Geschwindigkeit der Transmetallierung durchgeführt.…”