Journal ArticleDOI
Data-Driven Multi-Objective Optimization Tactics for Catalytic Asymmetric Reactions Using Bisphosphine Ligands.
Jordan J. Dotson,Lucy van Dijk,Jacob C. Timmerman,Samantha Grosslight,Richard C. Walroth,Francis Gosselin,Kurt Püntener,Kyle A. Mack,Matthew S. Sigman +8 more
TLDR
In this article , a machine learning workflow for the multi-objective optimization of catalytic reactions that employ chiral bisphosphine ligands was described through the optimization of two sequential reactions required in the asymmetric synthesis of an active pharmaceutical ingredient.Abstract:
Optimization of the catalyst structure to simultaneously improve multiple reaction objectives (e.g., yield, enantioselectivity, and regioselectivity) remains a formidable challenge. Herein, we describe a machine learning workflow for the multi-objective optimization of catalytic reactions that employ chiral bisphosphine ligands. This was demonstrated through the optimization of two sequential reactions required in the asymmetric synthesis of an active pharmaceutical ingredient. To accomplish this, a density functional theory-derived database of >550 bisphosphine ligands was constructed, and a designer chemical space mapping technique was established. The protocol used classification methods to identify active catalysts, followed by linear regression to model reaction selectivity. This led to the prediction and validation of significantly improved ligands for all reaction outputs, suggesting a general strategy that can be readily implemented for reaction optimizations where performance is controlled by bisphosphine ligands.read more
Citations
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Catalyst-Controlled Enantioselective and Regiodivergent Addition of Aryl Boron Nucleophiles to N-Alkyl Nicotinate Salts.
TL;DR: In this paper , it was shown that the regioselective addition of boron-based nucleophiles to pyridinium salts can be accomplished by the choice of a Rh catalyst.
Journal ArticleDOI
Modular synthesis of unsymmetric 1,3-diphosphinopropanes through sequential substitution reactions
Journal ArticleDOI
Charting the Chemical Reaction Space around a Multicomponent Combination: Controlled Access to a Diverse Set of Biologically Relevant Scaffolds
TL;DR: In this article , the authors describe unprecedented reactivity at the C-2 position of the imidazolone core to directly afford C, S, and N-derivatives featuring natural products (e.g. leucettamines), potent kinase inhibitors, and fluorescent probes with suitable optical and biological profiles.
Journal ArticleDOI
It Is Not All about the Ligands: Exploring the Hidden Potentials of tBu3P through Its Oxidative Addition Complex as the Precatalyst
TL;DR: A series of oxidative addition complexes with a general formula (tBu3P)Pd(Ar)X, as a class of precatalysts, were synthesized for challenging Suzuki-Miyaura coupling involving coupling partners, such as sensitive polyfluorinated arylboronic acids or their corresponding boronic esters, sterically hindered electrophiles, and sterically hindering nucleophiles as discussed by the authors .
Journal ArticleDOI
Charting the Chemical Reaction Space around a Multicomponent Combination: Controlled Access to a Diverse Set of Biologically Relevant Scaffolds.
Pau Nadal Rodríguez,Ouldouz Ghashghaei,Anna M. Schoepf,Samuel John Benson,Marc Vendrell,Rodolfo Lavilla +5 more
TL;DR: In this paper , the authors describe unprecedented reactivity at the C-2 position of the imidazolone core to directly afford C, S, and N-derivatives featuring natural products (e.g. leucettamines), potent kinase inhibitors, and fluorescent probes with suitable optical and biological profiles.
References
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Steric effects of phosphorus ligands in organometallic chemistry and homogeneous catalysis
Journal ArticleDOI
Automatic Chemical Design Using a Data-Driven Continuous Representation of Molecules
Rafael Gómez-Bombarelli,Jennifer N. Wei,David Duvenaud,José Miguel Hernández-Lobato,Benjamin Sanchez-Lengeling,Dennis Sheberla,Jorge Aguilera-Iparraguirre,Timothy D. Hirzel,Ryan P. Adams,Alán Aspuru-Guzik,Alán Aspuru-Guzik +10 more
TL;DR: In this article, a deep neural network was trained on hundreds of thousands of existing chemical structures to construct three coupled functions: an encoder, a decoder, and a predictor, which can generate new molecules for efficient exploration and optimization through open-ended spaces of chemical compounds.
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Automatic chemical design using a data-driven continuous representation of molecules
Rafael Gómez-Bombarelli,Jennifer N. Wei,David Duvenaud,José Miguel Hernández-Lobato,Benjamin Sanchez-Lengeling,Dennis Sheberla,Jorge Aguilera-Iparraguirre,Timothy D. Hirzel,Ryan P. Adams,Alán Aspuru-Guzik,Alán Aspuru-Guzik +10 more
TL;DR: A method to convert discrete representations of molecules to and from a multidimensional continuous representation that allows us to generate new molecules for efficient exploration and optimization through open-ended spaces of chemical compounds is reported.
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Synthesis of 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (BINAP), an atropisomeric chiral bis(triaryl)phosphine, and its use in the rhodium(I)-catalyzed asymmetric hydrogenation of .alpha.-(acylamino)acrylic acids
Journal ArticleDOI
SambVca: A Web Application for the Calculation of the Buried Volume of N‐Heterocyclic Carbene Ligands
Albert Poater,Biagio Cosenza,Andrea Correa,Simona Giudice,Francesco Ragone,Vittorio Scarano,Luigi Cavallo +6 more
TL;DR: In this article, a free web application for the calculation of the buried volume of NHC ligands is presented, which provides a graphic and user-friendly interface to the SambVca program.