A General Protocol for Addressing Speciation of the Active Catalyst Applied to Ligand-Accelerated Enantioselective C(sp³)–H Bond Arylation

Abstract

The potential role of dimeric catalyst species on or off the catalytic cycle is considered for a case of Pd-catalyzed C−H functionalization, leading to the development of a general experimental protocol that uses the reaction itself to report on the presence and role of dimeric species in asymmetric catalytic reactions.

3‐Mono‐Substituted BINOL Phosphoric Acids as Effective Organocatalysts in Direct Enantioselective Friedel–Crafts‐Type Alkylation of N‐Unprotected α‐Ketiminoester

“…In addition, the linear relationship between the enantiomeric excess of catalyst 2d and product 5a [Scheme 2, Reaction(2)],a sw ell as the first-order rate dependency on the concentration of catalyst 2d [Scheme 2, Reaction (3)],s uggests that catalyst 2d functions as monomeric species. [17] With these mechanistic insights, we performed ac omputational study of the reactions to explain the observede nantioselectivity.W ith am odified DFT calculation method of related phosphoric acid-catalyzed enantioselective reactions, [18] four transition states were located for the addition of 4a to 3 catalyzed by 2d,a nd the calculated enantiomeric excess (97 %f or (S)) from the differential transition state energies (DDG°S -R = À1.76 kcal mol À1 )w as in good agreement with the observed enantiomeric excess (93 %f or (S); DDG°S -R = À1.40 kcal mol À1 ). [18] Based on the most energetically accessible transition state structure leading to (S)-5a ( Figure 2), it is assumedt hat the CÀH-p interaction between the 2p osition of 4a and the anthranyl substituent of 2d was an important factor to stabilize the transition state, because the shortest length between the carbon and hydrogen atoms (2.83 )i ss maller than the sum of their Vand er Waals radii (2.90 ).…”

Mechanism of the Arene-Limited Nondirected C–H Activation of Arenes with Palladium

“…[34] The potential role of dinuclear Pd-species in Pd-pyridine, as well as Pd-N-acetyl amino acid systems, has been investigated intensively with both experimental and computational methods. [35], [36] Depending on the system studied, dinuclear or higher-order complexes have been found both as on-cycle and as off-cycle species. [36] In order to distinguish between mononuclear and oligonuclear species as active catalysts, kinetic measurements have been established as a highly useful tool.…”

“…[35], [36] Depending on the system studied, dinuclear or higher-order complexes have been found both as on-cycle and as off-cycle species. [36] In order to distinguish between mononuclear and oligonuclear species as active catalysts, kinetic measurements have been established as a highly useful tool. [36] We thus measured the influence of catalyst loading on the initial rate of the reaction using two different approaches.…”

“…[36] In order to distinguish between mononuclear and oligonuclear species as active catalysts, kinetic measurements have been established as a highly useful tool. [36] We thus measured the influence of catalyst loading on the initial rate of the reaction using two different approaches. First, we varied the loading of all catalyst components keeping the ratio between them constant as used under the optimized reaction conditions ( Figure 3A).…”

“…The results were analyzed using a non-linear least squares fit and the order in catalyst was determined to be 0.5. This broken order in catalyst below unity could be caused by (a) mononuclear active species that are in equilibrium with inactive higher order aggregates, [36] or (b) equilibria between mononuclear complexes with one (active) or two (inactive) pyridine ligands bound. [30] To distinguish between these scenarios, we determined the kinetic order of Pd(OAc)2, by varying only this component and providing a constant excess of both ligands ( Figure 3B).…”