Mechanistic Insights on Cooperative Asymmetric Multicatalysis Using Chiral Counterions

Abstract

Cooperative multicatalytic methods are steadily gaining popularity in asymmetric catalysis. The use of chiral Brønsted acids such as phosphoric acids in conjunction with a range of transition metals has been proven to be effective in asymmetric synthesis. However, the lack of molecular-level understanding and the accompanying ambiguity on the role of the chiral species in stereoinduction continues to remain an unresolved puzzle. Herein, we intend to disclose some novel transition state models obtained through DFT(B3LYP and M06) computations for a quintessential reaction in this family, namely, palladium-catalyzed asymmetric Tsuji-Trost allylation of aldehydes. The aldehyde is activated as an enamine by the action of a secondary amine (organocatalysis), which then adds to an activated Pd-allylic species (transition metal catalysis) generated through the protonation of allyic alcohol by chiral BINOL-phosphoric acid (Brønsted acid catalysis). We aim to decipher the nature of chiral BINOL-phosphates and their role in creating a quaternary chiral carbon atom in this triple catalytic system. The study reports the first transition state model capable of rationalizing chiral counterion-induced enantioselectivity. It is found that the chiral phosphate acts as a counterion in the stereocontrolling event rather than the conventional ligand mode.

Computational Studies of Synthetically Relevant Homogeneous Organometallic Catalysis Involving Ni, Pd, Ir, and Rh: An Overview of Commonly Employed DFT Methods and Mechanistic Insights

“…278 They reported that an achiral organocatalyst first activates the aldehyde as an enamine. Enantioselectivity is then induced through hydrogen bonding between the enamine nitrogen and a chiral BINOL−phosphate which acts more as a counterion than a ligand in the stereocontrolling transition state.…”

Iron/Brønsted Acid Catalyzed Asymmetric Hydrogenation: Mechanism and Selectivity‐Determining Interactions

“…a related C-H…O interaction between a chiral phosphoric acid and the triphenyl phosphine ligand of a transition-metal catalyst was identified to be involved in the stereocontrol of cooperative palladium-catalyzed asymmetric allylation. [37] A C-H…O interaction was also identified as selectivity-determining interaction in proline-catalyzed intramolecular aldol reactions.…”

“…asymmetric imine hydrogenation, [49] and by Sunoj and coworkers for cooperative palladium-catalyzed asymmetric allylation. [37] For the iron-Brønsted acid system investigated here, the selectivitydetermining interactions include electrostatic and dispersion interactions. C-H…O interactions appear particularly relevant ( Figure 8, Table 3).…”

“…[ 35 , 36 ] However, to our knowledge a similar analysis for iron-cyclopentadienone-catalysed hydrogenation in presence of a Brønsted acid has not yet been performed. As pointed out by Sunoj and coworkers, [24c] to date there are few computational transition state models of cooperative systems involving a transition metal and a Brønsted acid (a relevant study on cooperative palladium-catalyzed allylation was reported by Jindal and Sunoj [ 37 ] ; for a recent review see [24c]). The factors governing the stereocontrol of iron-Brønsted-acidcatalysed asymmetric imine hydrogenations are currently unknown.…”

Enantioselective Heck–Matsuda Arylations through Chiral Anion Phase‐Transfer of Aryl Diazonium Salts

“…[20,21] The Gibbs free energies of activation computed at the SMD (Toluene) /B3LYP-D3/6-31G**, SDD(Pd)//SMD (Toluene) /B3LYP-D3/6-31G**,LANL2DZ(Pd) level of theory for reductive elimination step and isomerization of 11 . The Gibbs free energy of activation for the reductive elimination (Figure 1a) was found to be 2.2 kcal/mol lower with a BINAM-phosphate than with a BINOL-phosphate (See Table S3, Supporting Information).…”