An Extraordinary Catalyst Allowing Time-Dependent Enantiodivergent Synthesis

Hedouin, Gaspard; Colobert, Françoise

doi:10.1016/j.chempr.2020.07.016

Cited by 1 publication

(1 citation statement)

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“…Stereochemically dynamic intermediates have been shown to allow various challenging transformations such as convergent chiral synthesis (e.g., via dynamic kinetic asymmetric transformations, DyKATs), − time-dependent stereodivergent processes, etc. Recent advances in stereodivergent dual catalysis have seen great success in exploiting the in situ isomerizations of stereochemically dynamic intermediates. − A representative example was provided by Zhang and Liao et al, who described a stereodivergent DyKAT of racemic unsymmetrical 1,3-disubstituted allylic esters with aldimine esters by means of Pd/Cu dual catalysis (Figure b) .…”

Section: Introductionmentioning

confidence: 99%

Ligand Effects on Isomerization/Bond-Formation Networks in Stereodivergent Pd/Cu Dual Catalysis Involving Stereochemically Dynamic Allylpalladium Intermediates

Li,

Zhang,

et al. 2023

ACS Catal.

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Recent advancements in enantio-/diastereodivergent dual catalysis are greatly empowered by stereochemically dynamic metal-allyl species. These in situ generated stereochemical mixtures span a highly convoluted network of isomerization and bond-formation pathways. While elucidation of these networks can offer valuable insights that aid the design of more efficient and controllable reactions utilizing stereochemically dynamic species as versatile intermediates, such a task has challenged both experiments and computations due to the combinatorial complexity and transient nature of the allylpalladium(II). Here, we report extensive computational studies with experimental validation that together provide full isomerization/bond-formation networks for two recent systems of stereodivergent Pd/Cu dual catalysis. We show that allylpalladium(II) can undergo a number of isomerization processes prior to C(sp3)–C(sp3) formation, and diastereoselection over the resulting diastereomeric mixture consisting of multiple syn-/anti-allylpalladium is independent of the copper-bound nucleophile. Moreover, critical ligand control over the stereochemical composition of allylpalladium(II) is disclosed, which is reliant upon the detailed positioning of ligand steric hindrance. Surprisingly, such an effect is crucial for the diastereoselection in a Pd/Cu dual-catalytic cross-coupling of 1,3-diene with aldimine esters. The studies showcase how variations in ligand structures cause distinct reaction flows in the reaction networks of Pd/Cu dual catalysis through the lens of network-level computational analysis.

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