Quantum Chemical Investigation of Dimerization in the Schlenk Equilibrium of Thiophene Grignard Reagents

Abstract

The Schlenk equilibrium of Grignard reagents describes the intricate relationships between monomers, aggregates, and exchange products. The core step of the Schlenk equilibrium, formally 2RMgX ⇌ R 2 Mg + MgX 2 , has been subject to computational studies of simple methyl Grignards and NMR determination of thermodynamics. These studies neglect the effect the R group may have on the accessibility of intermediates in the Schlenk equilibrium. In this study, computational reaction discovery tools were employed to thoroughly search the chemical space for feasible dimerizations and pathways to ligand exchange for thiophene Grignards. Three bridged dimers, μ-(Cl, C), μ-(Cl, Cl), and μ-Cl, were found to be vital intermediates, which are stabilized by πinteractions involving the thiophene group. These dimers are approximately as thermodynamically stable as the Grignard monomers and its ligand exchange products, and therefore, their reactivity should be considered when examining mechanisms for aryl Grignard or cross-coupling reactions.

Light Directs Monomer Coordination in Catalyst-Free Grignard Photopolymerization

“…Recent computational studies of aryl Grignard reagents have revealed stable dimeric aggregates that sequester reactive monomer and push the equilibrium away from the chain-bound structures required in our proposed mechanism . We identified two such dimeric aggregates for 1-MgBr (Figure S20).…”

“…To understand why this reaction fails, we performed calculations for monomer coordination to the thiophene dimer radical anion, 12 (Figure a; the hexyl chain is truncated to CH 3 ), which would be produced by oxidative dimerization of the corresponding Grignard monomer. Recent computational work by Zimmerman on the aggregation of thiophene Grignard reagents suggests that thiophenes such as 2-MgBr form stable solvate dimers . Such dimers would decrease reactivity by pushing the equilibrium away from the necessary monomer-coordinated radical anions.…”

“…Recent computational studies of Grignard solvates and their reactivities suggest that there are likely many structures of the Grignard monomer in solution, which are nearly degenerate in energy. 27,46 A study by Cascella relating these structures to reactivity with carbonyl electrophiles found a <2 kcal/mol difference between monomeric and dimeric solvates, suggesting that Grignard reactions may occur via an amalgamation of similar mechanisms. 46 Regardless of the many nuances of Grignard speciation in the experimental system, we believe that the mechanism in Scheme 4 provides a general framework for understanding the photopolymerization.…”

“…Recent computational work by Zimmerman on the aggregation of thiophene Grignard reagents suggests that thiophenes such as 2-MgBr form stable solvate dimers. 27 Such dimers would decrease reactivity by pushing the equilibrium away from the necessary monomer-coordinated radical anions. For the purposes of our model study, we will focus on the interactions of monomeric thiophene Grignard reagents with the dimer radical anion 12, but we acknowledge that monomer aggregation could also contribute to the low reactivity of electron-rich monomers in the photopolymerization.…”

“…Recent computational studies of aryl Grignard reagents have revealed stable dimeric aggregates that sequester reactive monomer and push the equilibrium away from the chain-bound structures required in our proposed mechanism. 27 We identified two such dimeric aggregates for 1-MgBr (Figure S20). These structures are >18 kcal/mol less stable than the bis-solvated monomer, likely due to the increased sterics of the benzotriazole structure compared to previously studied systems.…”