Computational Study on the C–Heteroatom Bond Formation via Stille Cross-Coupling Reaction: Differences between Organoheterostannanes Me₃SnAsPh₂vs Me₃SnPPh₂

Abstract

The formation of C−heteroatom bonds through the Stille cross-coupling reaction has been explored computationally within the density functional theory framework. To this end, the reaction profiles of the processes involving different aryl halides (PhCl, PhI) and heterostannanes (Me 3 SnZR 2 , Z = As, P; R = Ph, Me) in the presence of palladium catalyst have been investigated and compared to gain more insight into the differential reactivity observed experimentally. In addition, the main features of the reaction steps where the heterostannanes are involved, namely, the transmetalation and reductive elimination reactions, have been analyzed in detail. It was found that the overall relative reaction profile for the transmetalation step involving heterostannanes with Z = P is energetically favored over that involving species having Z = As, which agrees with the experimental observations. This can be mainly ascribed to the relative strength of the Sn−Z bond, which is broken during the transmetalation step (Sn−P < Sn−As).

The Stille Reaction, 38 Years Later

“…The two cyclic pathways, via the old TS , or the new TS (here), have the same kinetic dependences, and this case illustrates the convenience of combining calculations and experiment in mechanistic studies for a more accurate interpretation of the data. Other mechanistic DFT studies, , some of them involving heterostannanes (Me 3 SnZR 3 , Z = P, As; R = Ph, Me) as nucleophiles, also support the validity of the mechanistic proposal in Scheme . , It is, however, important to recall that DFT studies should never replace the primary value of experimental kinetic studies because the precision of calculated energies cannot be guaranteed. An error in the calculated activation energy of 1 kcal mol –1 , which looks unavoidable for metal-containing molecules, means roughly a one power of 10 error in the corresponding reaction rate, which can dramatically change the prediction of the preferred pathway …”

Mechanistic Insights into the Copper-Cocatalyzed Sonogashira Cross-Coupling Reaction: Key Role of an Anion

“…Two possibilities (with and without phosphine ligand dissociation) were considered in the transmetalation step. 21,39,40 The dissociation of I − ion from the Pd center of oxidative addition product 4 (Figure 1) to form cationic [PhPd(PPh 3 ) 2 ] + is highly endergonic (ΔG = +13.2 kcal/mol, ΔH = +24.1 kcal/mol). The dissociation of one phosphine ligand in 4 results in the complex [(PPh 3 )PdIPh] (3; Figure 1).…”

Palladium-Catalyzed Arsination Reactions and their Applications on the Synthesis of Arsine Ligands

“…Despite the broad amount of mechanistic studies focused on the Stille C-C bond-forming reaction, the first work on C-heteroatom bonds formation through the Stille crosscoupling reaction has been recently reported [59]. On this work, the formation of C-P and C-As bonds through the Pdcatalyzed Stille reaction was computationally explored within the Density Functional Theory (DFT) framework.…”

“…The overall relative reaction profile for the transmetalation step involving heterostannanes with Z = P is energetically favored than that involving species having Z = As, which agrees with the experimental observations. This observation can be mainly attributed to the relative strength of Sn-Z bond, which is broken during the transmetalation step (Sn-P < Sn-As) [59]. The process ends up with the irreversible reductive elimination step from the T-shaped tricoordinated intermediate 7As-P via transition state TS-7 (Figure 3) that leads to final reaction products.…”