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Title: A Simple, Multidimensional Approach to High-Throughput Discovery of Catalytic Reactions

Abstract

Transition metal complexes catalyze many important reactions that are employed in medicine, materials science, and energy production. Although high-throughput methods for the discovery of catalysts that would mirror related approaches for the discovery of medicinally active compounds have been the focus of much attention, these methods have not been sufficiently general or accessible to typical synthetic laboratories to be adopted widely. We report a method to evaluate a broad range of catalysts for potential coupling reactions with the use of simple laboratory equipment. Specifically, we screen an array of catalysts and ligands with a diverse mixture of substrates and then use mass spectrometry to identify reaction products that, by design, exceed the mass of any single substrate. Lastly, with this method, we discovered a copper-catalyzed alkyne hydroamination and two nickel-catalyzed hydroarylation reactions, each of which displays excellent functional-group tolerance.

Authors:
 [1];  [1]
  1. Univ. of Illinois, Urbana-Champaign, IL (United States). Dept. of Chemistry
Publication Date:
Research Org.:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
Sponsoring Org.:
USDOE; National Institutes of Health (NIH); Boehringer Ingelheim
OSTI Identifier:
1468801
Report Number(s):
LBNL-1007180
Journal ID: ISSN 0036-8075; ir:1007180
Grant/Contract Number:  
FG02-07ER15843; GM-55382
Resource Type:
Journal Article: Accepted Manuscript
Journal Name:
Science
Additional Journal Information:
Journal Volume: 333; Journal Issue: 6048; Journal ID: ISSN 0036-8075
Publisher:
AAAS
Country of Publication:
United States
Language:
English
Subject:
36 MATERIALS SCIENCE; 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY

Citation Formats

Robbins, Daniel W., and Hartwig, John F. A Simple, Multidimensional Approach to High-Throughput Discovery of Catalytic Reactions. United States: N. p., 2011. Web. doi:10.1126/science.1207922.
Robbins, Daniel W., & Hartwig, John F. A Simple, Multidimensional Approach to High-Throughput Discovery of Catalytic Reactions. United States. https://doi.org/10.1126/science.1207922
Robbins, Daniel W., and Hartwig, John F. 2011. "A Simple, Multidimensional Approach to High-Throughput Discovery of Catalytic Reactions". United States. https://doi.org/10.1126/science.1207922. https://www.osti.gov/servlets/purl/1468801.
@article{osti_1468801,
title = {A Simple, Multidimensional Approach to High-Throughput Discovery of Catalytic Reactions},
author = {Robbins, Daniel W. and Hartwig, John F.},
abstractNote = {Transition metal complexes catalyze many important reactions that are employed in medicine, materials science, and energy production. Although high-throughput methods for the discovery of catalysts that would mirror related approaches for the discovery of medicinally active compounds have been the focus of much attention, these methods have not been sufficiently general or accessible to typical synthetic laboratories to be adopted widely. We report a method to evaluate a broad range of catalysts for potential coupling reactions with the use of simple laboratory equipment. Specifically, we screen an array of catalysts and ligands with a diverse mixture of substrates and then use mass spectrometry to identify reaction products that, by design, exceed the mass of any single substrate. Lastly, with this method, we discovered a copper-catalyzed alkyne hydroamination and two nickel-catalyzed hydroarylation reactions, each of which displays excellent functional-group tolerance.},
doi = {10.1126/science.1207922},
url = {https://www.osti.gov/biblio/1468801}, journal = {Science},
issn = {0036-8075},
number = 6048,
volume = 333,
place = {United States},
year = {Thu Sep 08 00:00:00 EDT 2011},
month = {Thu Sep 08 00:00:00 EDT 2011}
}

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Free Publicly Available Full Text
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Cited by: 181 works
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Works referenced in this record:

Electrospray Ionization Tandem Mass Spectrometry in High-Throughput Screening of Homogeneous Catalysts
journal, June 2003


Recent advances in the discovery of organometallic catalysts using high-throughput screening assays
journal, June 2003


Development and Initial Application of a Hybridization-Independent, DNA-Encoded Reaction Discovery System Compatible with Organic Solvents
journal, December 2007


Preparation of Enamides via Palladium-Catalyzed Amidation of Enol Tosylates
journal, March 2005


Scope of the Suzuki−Miyaura Cross-Coupling Reactions of Potassium Heteroaryltrifluoroborates
journal, February 2009


Palladium-catalyzed hydroarylation of alkynes with arylboronic acids
journal, March 2010


Cobalt(II)-Catalyzed Regio- and Stereoselective Hydroarylation of Alkynes with Organoboronic Acids
journal, November 2008


Ruthenium-Catalyzed N -Alkylation of Amines and Sulfonamides Using Borrowing Hydrogen Methodology
journal, February 2009


Nickel-Catalyzed Arylcyanation of Alkynes
journal, November 2004


Syntheses, structure and ethylene polymerization behavior of β-diiminato titanium complexes
journal, April 2006


A General Solution for Unstable Boronic Acids: Slow-Release Cross-Coupling from Air-Stable MIDA Boronates
journal, May 2009


Discovery of Chemical Reactions through Multidimensional Screening
journal, February 2007


A New Palladium Precatalyst Allows for the Fast Suzuki−Miyaura Coupling Reactions of Unstable Polyfluorophenyl and 2-Heteroaryl Boronic Acids
journal, October 2010


The ?Nickel Effect?
journal, December 1973


Search for Chiral Catalysts Through Ligand Diversity: Substrate-Specific Catalysts and Ligand Screening on Solid Phase
journal, September 1997


Intermolecular Hydroamination of Alkynes Catalyzed by Dimethyltitanocene
journal, November 1999


Hydroamination: Direct Addition of Amines to Alkenes and Alkynes
journal, September 2008


New aryl/heteroaryl CN bond cross-coupling reactions via arylboronic acid/cupric acetate arylation
journal, May 1998


Phosphorus-Stabilized Geminal Dianions
journal, October 2006


Spectroscopic Evidence for the Direct Coordination of the Pertechnetate Anion to the Uranyl Cation in [UO 2 (TcO 4 )(DPPMO 2 ) 2 ] +
journal, September 2004


Reaction discovery enabled by DNA-templated synthesis and in vitro selection
journal, September 2004


Mass Spectrometric Screening of Enantioselective Diels–Alder Reactions
journal, April 2008


Isotope or mass encoding of combinatorial libraries
journal, August 1996


Discovery of Novel Catalysts for Alkene Epoxidation from Metal-Binding Combinatorial Libraries
journal, April 1999


Efficient Synthesis of γ,δ-Alkynyl-β-amino Acid Derivatives by a New Copper-Catalyzed Amine-Alkyne-Alkyne Addition Reaction
journal, October 2008


Olefin metathesis: chance favors those minds that are best prepared
journal, March 1991


Rhodium-Catalyzed Hydroarylation of Alkynes with Arylboronic Acids:  1,4-Shift of Rhodium from 2-Aryl-1-alkenylrhodium to 2-Alkenylarylrhodium Intermediate
journal, October 2001


Combinatorial Ligand Development Based on Mass Spectrometric Screening and a Double Mass-Labeling Strategy
journal, March 2008


Tandem Processes Identified from Reaction Screening: Nucleophilic Addition to Aryl N -Phosphinylimines Employing La(III)-TFAA Activation
journal, May 2010


Mass spectrometric assay of polymerization catalysts for combinational screening
journal, January 2000


Discovery of Chiral Catalysts through Ligand Diversity: Ti-Catalyzed Enantioselective Addition of TMSCN tomeso Epoxides
journal, August 1996


Highly Efficient Cu(I)-Catalyzed Synthesis of N -Heterocycles through a Cyclization-Triggered Addition of Alkynes
journal, January 2010


Using Intelligent/Random Library Screening To Design Focused Libraries for the Optimization of Homogeneous Catalysts:  Ullmann Ether Formation
journal, May 2000


A Mass Spectrometric Labeling Strategy for High-Throughput Reaction Evaluation and Optimization: Exploring C−H Activation
journal, January 2001


General Zinc-Catalyzed Intermolecular Hydroamination of Terminal Alkynes
journal, April 2008


Nickel-Catalyzed Arylcyanation of Alkynes.
journal, March 2005


Preparation of Enamides via Palladium-Catalyzed Amidation of Enol Tosylates.
journal, August 2005


Mass Spectrometric Screening of Enantioselective Diels–Alder Reactions
journal, April 2008


Works referencing / citing this record:

Catalytic Alkyne Hydroarylation Using Arylboron Reagents, Aryl Halides, and Congeners
book, January 2017


Selective Hydroarylation of 1,3-Diynes Using a Dimeric Manganese Catalyst: Modular Synthesis of Z -Enynes
journal, September 2018


Hochdurchsatzstrategien zur Entdeckung und Optimierung katalytischer Reaktionen
journal, March 2019


Reaction Discovery by Using a Sandwich Immunoassay
journal, May 2012


Exploration of Forbidden Povarov Processes as a Source of Unexpected Reactivity: A Multicomponent Mannich-Ritter Transformation
journal, May 2012


Reductive Cross-Coupling of Conjugated Arylalkenes and Aryl Bromides with Hydrosilanes by Cooperative Palladium/Copper Catalysis
journal, April 2016


Accelerated Discovery in Photocatalysis using a Mechanism-Based Screening Method
journal, March 2016


Picomole-Scale Real-Time Photoreaction Screening: Discovery of the Visible-Light-Promoted Dehydrogenation of Tetrahydroquinolines under Ambient Conditions
journal, June 2016


Selective Hydroarylation of 1,3-Diynes Using a Dimeric Manganese Catalyst: Modular Synthesis of Z -Enynes
journal, September 2018


High Throughput Strategies for the Discovery and Optimization of Catalytic Reactions
journal, May 2019


Data Mining the C−C Cross‐Coupling Genome
journal, May 2019


A Supramolecular Palladium Catalyst Displaying Substrate Selectivity by Remote Control
journal, December 2018


Streamlined Asymmetric Reaction Development: A Case Study with Isatins
journal, September 2009


Alkene Hydrogenation Catalyzed by Nickel Hydride Complexes of an Aliphatic PNP Pincer Ligand
journal, August 2012


Nickel-Catalyzed Directed Hydroarylation of Alkynes with Boronic Acids: Nickel-Catalyzed Directed Hydroarylation of Alkynes with Boronic Acids
journal, November 2018


Three-component reaction discovery enabled by mass spectrometry of self-assembled monolayers
journal, December 2011


Label-assisted mass spectrometry for the acceleration of reaction discovery and optimization
journal, March 2013


A robustness screen for the rapid assessment of chemical reactions
journal, June 2013


Contemporary screening approaches to reaction discovery and development
journal, September 2014


New ligands for nickel catalysis from diverse pharmaceutical heterocycle libraries
journal, August 2016


How to explore chemical space using algorithms and automation
journal, January 2019


Holistic prediction of enantioselectivity in asymmetric catalysis
journal, July 2019


Ambient arylmagnesiation of alkynes catalysed by ligandless nickel(ii)
journal, January 2013


Experiment and computation: a combined approach to study the reactivity of palladium complexes in oxidation states 0 to iv
journal, January 2014


Simultaneous solvent screening and reaction optimization in microliter slugs
journal, January 2015


Ultrafast chiral separations for high throughput enantiopurity analysis
journal, January 2017


Ni-Catalyzed regio- and stereoselective addition of arylboronic acids to terminal alkynes with a directing group tether
journal, January 2017


Nickel-catalyzed cyclization of alkyne-nitriles with organoboronic acids involving anti-carbometalation of alkynes
journal, January 2016


Ligand libraries for high throughput screening of homogeneous catalysts
journal, January 2018


Iridium complexes catalysed the selective dehydrogenation of glucose to gluconic acid in water
journal, January 2018


Discovery of an  -Amino C-H Arylation Reaction Using the Strategy of Accelerated Serendipity
journal, November 2011


Nanomole-scale high-throughput chemistry for the synthesis of complex molecules
journal, November 2014


A data-intensive approach to mechanistic elucidation applied to chiral anion catalysis
journal, February 2015


Snap deconvolution: An informatics approach to high-throughput discovery of catalytic reactions
journal, July 2017


Inverse molecular design using machine learning: Generative models for matter engineering
journal, July 2018


Reaction Discovery by Using a Sandwich Immunoassay
journal, May 2012


Computational Ligand Design for the Reductive Elimination of ArCF 3 from a Small Bite Angle Pd II Complex: Remarkable Effect of a Perfluoroalkyl Phosphine
journal, May 2014


Tandem Use of Optical Sensing and Machine Learning for the Determination of Absolute Configuration, Enantiomeric and Diastereomeric Ratios, and Concentration of Chiral Samples
journal, December 2019


Prediction of higher-selectivity catalysts by computer-driven workflow and machine learning
journal, January 2019


Machine learning meets volcano plots: Computational discovery of cross-coupling catalysts
text, January 2018


Exploration of Forbidden Povarov Processes as a Source of Unexpected Reactivity: A Multicomponent Mannich-Ritter Transformation
journal, May 2012