LG

Machine learning algorithms are currently emerging as powerful tools in all areas of science. This review covers atomistic machine learning approaches in chemistry beyond the conventional data-driven perspective.

Abstract

Machine learning (ML) algorithms are currently emerging as powerful tools in all areas of science. Conventionally, ML is understood as a fundamentally data-driven endeavour. Unfortunately, large well-curated databases are sparse in chemistry. In this contribution, I therefore review science-driven ML approaches which do not rely on “big data”, focusing on the atomistic modelling of materials and molecules. In this context, the term science-driven refers to approaches that begin with a scientific question and then ask what training data and model design choices are appropriate. As key features of science-driven ML, the automated and purpose-driven collection of data and the use of chemical and physical priors to achieve high data-efficiency are discussed. Furthermore, the importance of appropriate model evaluation and error estimation is emphasized.

A predictive DFT study of L→Al(ORF) ₃ (L=Lewis bases) adducts allowed the identification of (iPr₂S)→Al(ORF)₃ as a “stable yet reactive” adduct, able to act as a masked Lewis superacid. It provides a novel strategy to use M-ORF/L→Al(ORF)₃ couples to generate catalytically active M+ centers featuring weakly coordinating aluminate counter anion.

Abstract

A DFT study of several L→Al(OR^F)₃ (L=Lewis bases) adducts allowed the identification of ( ⁱ Pr₂S)→Al(OR^F)₃ 1-S ⁱ Pr₂ as a “stable yet reactive” adduct. 1-S ⁱ Pr₂ was shown to act as a masked Lewis superacid able to release Al(OR^F)₃ under mild conditions. It could be used to abstract a OR^F− ligand from (bipyMe₂)Ni(OR^F)₂ (bipyMe₂ : 6,6’-dimethyl-2,2’-dipyridyl) and generate the nickel alkoxide complex [(bipyMe₂)Ni(OR^F)( ⁱ Pr₂S)]⁺[(R^FO)₃Al−F−Al(OR^F)₃]⁻ 5. Ligand exchange of ⁱ Pr₂S by Ph₃P yielded [(bipyMe₂)Ni(OR^F)(PPh₃)]⁺[(R^FO)₃Al−F−Al(OR^F)₃]⁻ 6.

By the Bi: The bismuth cation [BiDipp₂]⁺, stabilized by an [SbF₆]⁻ counteranion, has been synthesized, isolated and fully characterized (Dipp=2,6-iPr₂-C₆H₃). A detailed comparison with [BiMe₂(SbF₆)] highlights the impact of steric bulk on bismuth-based Lewis acidity. Differences in their Lewis acidity have been rationalized, and their reactivity towards [PF₆]⁻ as well as Lewis pair formations have been studied.

Abstract

The molecular compound [BiDipp₂(SbF₆)], containing the bulky, donor-free bismuth cation [BiDipp₂]⁺ has been synthesized and fully characterized (Dipp=2,6-iPr₂-C₆H₃). Using its methyl analog [BiMe₂(SbF₆)] as a second reference point, the impact of steric bulk on bismuth-based Lewis acidity was investigated in a combined experimental (Gutmann-Beckett and modified Gutmann-Beckett methods) and theoretical approach (DFT calculations). Reactivity studies of the bismuth cations towards [PF₆]⁻ and neutral Lewis bases such as isocyanides C≡NR’ revealed facile fluoride ion abstraction and straightforward Lewis pair formation, respectively. The first examples of compounds featuring bismuth-bound isocyanides have been isolated and fully characterized.

Bioorthogonal chemistry refers to reactions that can proceed in biological systems without interfering with biological processes. It has enabled the study of biomolecules in their native environment and has facilitated advanced imaging and diagnostic applications. In their Review (DOI: 10.1002/chem.202203942), M. M. A. Mitry, F. Greco and H. M. I. Osborn critically appraise the suitability of bioorthogonal reactions for in vivo applications. Areas of focus are chemical reactions and the targeting mechanisms used to deliver the bioorthogonal reactions’ components.

Novel heteroleptic copper(I) complexes based on the tetraazaphenanthrene ligand were synthesized and extensively studied. The correlation of the properties to the substitution of the diimine ligand and their impact on the photoreactivity of complexes in the presence of N,N’-diisopropylethylamine are rationalized, overall providing useful structure-property relationships for copper complexes as photoredox catalysts.

Abstract

A new family of heteroleptic diimine-diphosphine copper(I) complexes is reported, with six new complexes compared to benchmark [Cu(bcp)(DPEPhos)]PF₆. These new complexes are based on 1,4,5,8-tetraazaphenanthrene (TAP) ligands with representative electronic properties as well as substitution patterns and DPEPhos and XantPhos as diphosphine ligands. Their photophysical and electrochemical properties were investigated and correlated with the number and position of substituents on the TAP ligands. Stern-Volmer studies using Hünig's base as reductive quencher demonstrated the influence of the complex photoreduction potential and of the excited state lifetime on the photoreactivity. This study refines the structure-property relationship profile for heteroleptic copper(I) complexes and confirms that such profiles are of high interest to design new copper complexes as optimized photoredox catalysts.

Transition-metal-catalyzed asymmetric carbon-carbon bond formation to forge phosphonates with an α-chiral carbon center through C(sp³)−C(sp³) and C(sp²)−C(sp³) couplings has been successful. However, the enantioselective C(sp)−C(sp³) coupling has not yet been disclosed. Reported herein is an unprecedented enantioconvergent cross-coupling of alkynyl bromides and α-bromo phosphonates to deliver chiral α-alkynyl phosphonates.

Abstract

Transition-metal-catalyzed asymmetric carbon−carbon bond formation to forge phosphonates with an α-chiral carbon center through C(sp³)−C(sp³) and C(sp²)−C(sp³) couplings has been successful. However, the enantioselective C(sp)−C(sp³) coupling has not yet been disclosed. Reported herein is an unprecedented enantioconvergent cross-coupling of alkynyl bromides and α-bromo phosphonates to deliver chiral α-alkynyl phosphonates.

Chlorine is an indispensable base chemical that is used to produce numerous materials. To enable the chlorine industry to harvest renewable energies, a safe chlorine storage is of central importance. More recently, trichlorides, [Cl₃]⁻, have evolved to a key technique for the storage of chlorine and for important chlorination reactions. In this minireview, the potential of trichlorides for academic research and the chlorine industry are outlined.

Abstract

Chlorine plays a central role for the industrial production of numerous materials with global relevance. More recently, polychlorides have been evolved from an area of academic interest to a research topic with enormous industrial potential. In this minireview, the value of trichlorides for chlorine storage and chlorination reactions are outlined. Particularly, the inexpensive ionic liquid [NEt₃Me][Cl₃] shows a similar and sometimes even advantageous reactivity compared to chlorine gas, while offering a superior safety profile. Used as a chlorine storage, [NEt₃Me][Cl₃] could help to overcome the current limitations of storing and transporting chlorine in larger quantities. Thus, trichlorides could become a key technique for the flexibilization of the chlorine production enabling an exploitation of renewable, yet fluctuating, electrical energy. As the loaded storage, [NEt₃Me][Cl₃], is a proven chlorination reagent, it could directly be employed for downstream processes, paving the path to a more practical and safer chlorine industry.

Nature Communications, Published online: 22 December 2022; doi:10.1038/s41467-022-35541-6

Ylide functionalized phosphines were tailored supported by computational inverse catalyst design to fit the requirements of mild Hiyama couplings of aryl chlorides. YPhos/Pd catalyst is highly efficient for the coupling with aryl chlorides in general, and the reaction shows excellent functional group compatibility.

Abstract

Palladium-catalyzed couplings of silicon enolates with aryl electrophiles are of great synthetic utility, but often limited to expensive bromide substrates. A comparative experimental study confirmed that none of the established ligand systems allows to couple inexpensive aryl chlorides with α-trimethylsilyl alkylnitriles. In contrast, ylide functionalized phosphines (YPhos) led to encouraging results. A statistical model was developed that correlates the reaction yields with ligand features. It was employed to predict catalyst structures with superior performance. With this cheminformatics approach, YPhos ligands were tailored specifically to the demands of Hiyama couplings. The newly synthesized ligands displayed record-setting activities, enabling the elusive coupling of aryl chlorides with α-trimethylsilyl alkyl nitriles. The preparative utility of the catalyst system was demonstrated by the synthesis of pharmaceutically meaningful α-aryl alkylnitriles, α-arylcarbonyls and biaryls.

Unprotected β-arylethylamines were directly accessed via 1,2-aminoarylation of alkenes under operationally simple conditions, thanks to a cooperative effect between an iron (II) catalyst and the solvent hexafluoroisopropanol. This one-pot sequential protocol did not require pre-activated (hetero)arenes and proved compatible with a broad range of drug-oriented functional groups.

Abstract

β-Arylethylamines are prevalent structural motifs in molecules exhibiting biological activity. Here we report a sequential one-pot protocol for the 1,2-aminoarylation of alkenes with hydroxylammonium triflate salts and (hetero)arenes. Unlike existing methods, this reaction provides a direct entry to unprotected β-arylethylamines with remarkable functional group tolerance, allowing key drug-oriented functional groups to be installed in a two-step process. The use of hexafluoroisopropanol as a solvent in combination with an iron(II) catalyst proved essential to reaching high-value nitrogen-containing molecules.