From desktop to benchtop with automated computational workflows for computer-aided design in asymmetric catalysis

Patrascu, Mihai Burai; Pottel, Joshua; Pinus, Sharon; Bezanson, Michelle; Norrby, Per‐Ola; Moitessier, Nicolas

doi:10.1038/s41929-020-0468-3

Cited by 45 publications

(44 citation statements)

References 56 publications

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“…While high-throughput experimentation allows for many different reaction conditions to be tested at once, this method still remains costly, especially for testing many different ligands 2,3 . Computational methods can not only predict which ligands would give the best results, reducing the time and cost needed to find the best catalyst 4 , but also give insight into the steric and electronic interactions that promote high stereoselectivity. Given the small energy differences involved, the computational methods need to be highly accurate while being fast enough to be useful for the synthetic chemist.…”

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confidence: 99%

Proofreading experimentally assigned stereochemistry through Q2MM predictions in Pd-catalyzed allylic aminations

et al. 2021

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The palladium-catalyzed enantioselective allylic substitution by carbon or nitrogen nucleophiles is a key transformation that is particularly useful for the synthesis of bioactive compounds. Unfortunately, the selection of a suitable ligand/substrate combination often requires significant screening effort. Here, we show that a transition state force field (TSFF) derived by the quantum-guided molecular mechanics (Q2MM) method can be used to rapidly screen ligand/substrate combinations. Testing of this method on 77 literature reactions revealed several cases where the computationally predicted major enantiomer differed from the one reported. Interestingly, experimental follow-up led to a reassignment of the experimentally observed configuration. This result demonstrates the power of mechanistically based methods to predict and, where necessary, correct the stereochemical outcome.

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confidence: 99%

Proofreading experimentally assigned stereochemistry through Q2MM predictions in Pd-catalyzed allylic aminations

et al. 2021

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“…Gratifyingly, it could achieve accuracies within ~1 kcal/mol and provided rapid analysis and a user‐friendly working environment. Overall, this technology is expected to accelerate catalyst and reaction discovery 166 …”

Section: Experimental and Computational Methods To Investigate The Me...mentioning

confidence: 99%

“…Overall, this technology is expected to accelerate catalyst and reaction discovery. 166 Moreover, the rapid development of data-driven approaches and related algorithms have facilitated computational chemists with the mechanistic investigation. Commonly, mechanistic exploration is performed based on quantum mechanical calculations to map out the potential energy surface and main reaction pathways based on the experimental findings.…”

Section: Automated Systems Combined With Data-driven Approachesmentioning

confidence: 99%

Mechanisms, challenges, and opportunities of dual Ni/photoredox‐catalyzed C(sp²)–C(sp³) cross‐couplings

Yuan

Gutiérrez

2021

WIREs Comput Mol Sci

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The merging of photoredox and nickel catalysis has revolutionized the field of C–C cross‐coupling. However, in comparison to the development of synthetic methods, detailed mechanistic investigations of these catalytic systems are lagging. To improve the mechanistic understanding, computational tools have emerged as powerful tools to elucidate the factors controlling reactivity and selectivity in these complex catalytic transformations. Based on the reported computational studies, it appears that the mechanistic picture of catalytic systems is not generally applicable, but is rather dependent on the specific choice of substrate, ligands, photocatalysts, etc. Given the complexity of these systems, the need for more accurate computational methods, readily available and user‐friendly dynamics simulation tools, and data‐driven approaches is clear in order to understand at the molecular level the mechanisms of these transformations. In particular, we anticipate that such improvement of theoretical methods will become crucial to advance the understanding of excited‐state properties and dynamics of key species, as well as to enable faster and unbiased exploration of reaction pathways. Further, with greater collaboration between computational, experimental, and spectroscopic communities, the mechanistic investigation of photoredox/Ni dual‐catalytic reactions is expected to thrive quickly, facilitating the design of novel catalytic systems and promoting our understanding of the reaction selectivity. This article is categorized under: Structure and Mechanism > Reaction Mechanisms and Catalysis Electronic Structure Theory > Density Functional Theory Molecular and Statistical Mechanics > Molecular Dynamics and Monte‐Carlo Methods

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“…While high-throughput experimentation allows for many different reaction conditions to be tested at once, this method still remains costly, especially for testing many different ligands. 2 Computational methods can not only predict which ligands would give the best results, reducing the time and cost needed to find the best catalyst, 3 but also give insight into the steric and electronic interactions that promote high stereoselectivity. Given the small energy differences involved, the computational methods need to be highly accurate while being fast enough to be useful for the synthetic chemist.…”

Section: Main Textmentioning

confidence: 99%

Proofreading Experimentally Assigned Stereochemistry Through Q2MM Predictions in Pd-Catalyzed Allylic Aminations

Wahlers¹,

Margalef²,

Hansen³

et al. 2021

Preprint

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From desktop to benchtop with automated computational workflows for computer-aided design in asymmetric catalysis

Cited by 45 publications

References 56 publications

Proofreading experimentally assigned stereochemistry through Q2MM predictions in Pd-catalyzed allylic aminations

Proofreading experimentally assigned stereochemistry through Q2MM predictions in Pd-catalyzed allylic aminations

Mechanisms, challenges, and opportunities of dual Ni/photoredox‐catalyzed C(sp²)–C(sp³) cross‐couplings

Proofreading Experimentally Assigned Stereochemistry Through Q2MM Predictions in Pd-Catalyzed Allylic Aminations

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From desktop to benchtop with automated computational workflows for computer-aided design in asymmetric catalysis

Cited by 45 publications

References 56 publications

Proofreading experimentally assigned stereochemistry through Q2MM predictions in Pd-catalyzed allylic aminations

Proofreading experimentally assigned stereochemistry through Q2MM predictions in Pd-catalyzed allylic aminations

Mechanisms, challenges, and opportunities of dual Ni/photoredox‐catalyzed C(sp2)–C(sp3) cross‐couplings

Proofreading Experimentally Assigned Stereochemistry Through Q2MM Predictions in Pd-Catalyzed Allylic Aminations

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Mechanisms, challenges, and opportunities of dual Ni/photoredox‐catalyzed C(sp²)–C(sp³) cross‐couplings