Applying statistical modeling strategies to sparse datasets in synthetic chemistry

Science Advances, Journal Year: 2025, Volume and Issue: 11(1)

Published: Jan. 1, 2025

The application of statistical modeling in organic chemistry is emerging as a standard practice for probing structure-activity relationships and predictive tool many optimization objectives. This review aimed tutorial those entering the area chemistry. We provide case studies to highlight considerations approaches that can be used successfully analyze datasets low data regimes, common situation encountered given experimental demands Statistical hinges on (what being modeled), descriptors (how are represented), algorithms modeled). Herein, we focus how various reaction outputs (e.g., yield, rate, selectivity, solubility, stability, turnover number) structures binned, heavily skewed, distributed) influence choice algorithm constructing chemically insightful models.

Language: Английский

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Stereoconvergent and -divergent Synthesis of Tetrasubstituted Alkenes by Nickel-Catalyzed Cross-Couplings

Journal of the American Chemical Society, Journal Year: 2021, Volume and Issue: 143(45), P. 19078 - 19090

Published: Nov. 4, 2021

We report the development of a method to diastereoselectively access tetrasubstituted alkenes via nickel-catalyzed Suzuki-Miyaura cross-couplings enol tosylates and boronic acid esters. Either diastereomeric product was selectively accessed from mixture tosylate starting material diastereomers in convergent reaction by judicious choice ligand conditions. A similar protocol also enabled divergent synthesis each isomer diastereomerically pure tosylates. Notably, high-throughput optimization monophosphine ligands guided chemical space analysis kraken library ensure diverse selection examined. Stereoelectronic results provided insight into requirements for reactive selective this transformation. The synthetic utility optimized catalytic system then probed stereoselective various alkenes, with yields up 94% ratios 99:1 Z/E 93:7 E/Z observed. Moreover, detailed computational experimental mechanistic studies key insights nature underlying isomerization process impacting selectivity cross-coupling.

Language: Английский

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Structure–Reactivity Relationships of Buchwald-Type Phosphines in Nickel-Catalyzed Cross-Couplings

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(42), P. 19635 - 19648

Published: Oct. 17, 2022

The dialkyl-ortho-biaryl class of phosphines, commonly known as Buchwald-type ligands, are among the most important phosphines in Pd-catalyzed cross-coupling. These ligands have also been successfully applied to several synthetically valuable Ni-catalyzed cross-coupling methodologies and, demonstrated this work, top performing Suzuki Miyaura Coupling (SMC) and C-N coupling reactions, even outperforming employed bisphosphines like dppf many circumstances. However, little is about their structure-reactivity relationships (SRRs) with Ni, limited examples well-defined, catalytically relevant Ni complexes exist. In we report analysis phosphine SRRs four representative reactions. Our study was guided by data-driven classification analysis, which together mechanistic organometallic studies structurally characterized Ni(0), Ni(I), Ni(II) allowed us rationalize reactivity patterns catalysis. Overall, expect that will serve a platform for further exploration ligand organonickel chemistry well development new methodologies.

Language: Английский

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A reactivity model for oxidative addition to palladium enables quantitative predictions for catalytic cross-coupling reactions

Chemical Science, Journal Year: 2022, Volume and Issue: 13(12), P. 3477 - 3488

Published: Jan. 1, 2022

Making accurate, quantitative predictions of chemical reactivity based on molecular structure is an unsolved problem in synthesis, particularly for complex molecules. We report approach to prediction catalytic reactions structure-reactivity models a key step common many mechanisms. demonstrate this with mechanistically model the oxidative addition (hetero)aryl electrophiles palladium(0), which myriad processes. This links simple descriptors relative rates 79 substrates, including chloride, bromide and triflate leaving groups. Because often controls rate and/or selectivity palladium-catalyzed reactions, can be used make about reaction outcomes. Demonstrated applications include multivariate linear initial Sonogashira coupling successful site-selectivity Suzuki, Buchwald-Hartwig, Stille multihalogenated substrates relevant synthesis pharmaceuticals natural products.

Language: Английский

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Genetic Optimization of Homogeneous Catalysts

Chemistry - Methods, Journal Year: 2022, Volume and Issue: 2(6)

Published: March 4, 2022

Abstract We present the NaviCatGA package, a versatile genetic algorithm capable of optimizing molecular catalyst structures using well‐suited fitness functions to achieve set targeted properties. The flexibility and generality this tool are validated demonstrated with two examples: i) Ligand optimization exploration for Ni‐catalyzed aryl‐ether cleavage manipulating SMILES function derived from volcano plots, ii) multi‐objective (i. e., activity/selectivity) bipyridine N,N ‐dioxide Lewis basic organocatalysts asymmetric propargylation benzaldehyde 3D fragments. show that evolutionary optimization, enabled by NaviCatGA, is an efficient way accelerating discovery through bypassing combinatorial scaling issues incorporating compelling chemical constraints.

Language: Английский

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Design and Application of a Screening Set for Monophosphine Ligands in Cross-Coupling

ACS Catalysis, Journal Year: 2022, Volume and Issue: 12(13), P. 7773 - 7780

Published: June 16, 2022

In reaction discovery, the search space of discrete parameters such as catalyst structure is often not explored systematically. We have developed a tool set to aid optimal catalysts in context phosphine ligands. A virtual library, kraken, which representative monodentate P(III)-ligand chemical space, was utilized basis represent ligands continuous variables. Using dimensionality reduction and clustering techniques, we suggested Phosphine Optimization Screening Set (PHOSS) 32 commercially available that samples this completely evenly. present application screening identification active for various cross-coupling reactions show how well-distributed sampling facilitates catalysts. Furthermore, demonstrate proximity ligand can be useful guide further explore when very few are known.

Language: Английский

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Atropisomeric Phosphine Ligands Bearing C–N Axial Chirality: Applications in Enantioselective Suzuki–Miyaura Cross-Coupling Towards the Assembly of Tetra-ortho-Substituted Biaryls

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(32), P. 14864 - 14873

Published: Aug. 3, 2022

Biaryl phosphines bearing C(Ar)–C(Ar) axial chirality are commonly known and have been successfully applied in many asymmetric catalyses. Nevertheless, the development of a chiral ligand having an axially C(Ar)–N backbone remains elusive due to its undesirable less restricted rotational barrier. In fact, it is highly attractive overcome this challenge as incorporation N-donor component at axis more favorable toward transient metal coordination, thus, better outcome stereocommunication anticipated approaching substrates. Herein, we present rational design new collection featuring C–N their applications enantioselective Suzuki–Miyaura cross-coupling for accessing steric hindered tetra-ortho-substituted biaryls (26 examples up 98:2 er). It worth noting that embodied carbazolyl framework crucial succeed reaction, by fruitful relief bulky substrate coordination transmetalation via fleeting Pd–N jumping Pd-π fashion. DFT calculation reveals interesting Pd-arene-walking characteristic across plane attaining lower energy-preferred route catalytic cycle. The theoretical study predicts stereooutcome matches enantioselectivity with experimental results.

Language: Английский

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When machine learning meets molecular synthesis

Trends in Chemistry, Journal Year: 2022, Volume and Issue: 4(10), P. 863 - 885

Published: Aug. 31, 2022

Language: Английский

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Machine Learning for Chemistry: Basics and Applications

Engineering, Journal Year: 2023, Volume and Issue: 27, P. 70 - 83

Published: July 31, 2023

The past decade has seen a sharp increase in machine learning (ML) applications scientific research. This review introduces the basic constituents of ML, including databases, features, and algorithms, highlights few important achievements chemistry that have been aided by ML techniques. described databases include some most popular chemical for molecules materials obtained from either experiments or computational calculations. Important two-dimensional (2D) three-dimensional (3D) features representing environment solids are briefly introduced. Decision tree deep neural network algorithms overviewed to emphasize their frameworks typical application scenarios. Three fields discussed: ① retrosynthesis, which predicts likely routes organic synthesis; ② atomic simulations, utilize potential accelerate energy surface sampling; ③ heterogeneous catalysis, assists various aspects catalytic design, ranging synthetic condition optimization reaction mechanism exploration. Finally, prospect on future is provided.

Language: Английский

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%V_Bur index and steric maps: from predictive catalysis to machine learning

Chemical Society Reviews, Journal Year: 2023, Volume and Issue: 53(2), P. 853 - 882

Published: Dec. 19, 2023

Steric indices are parameters used in chemistry to describe the spatial arrangement of atoms or groups molecules.

Language: Английский

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