title: Catalyst selection based on intermediate stability measured by mass spectrometry.
abstract: The power of natural selection through survival of the fittest is nature's ultimate tool for the improvement and advancement of species. To apply this concept in catalyst development is attractive and may lead to more rapid discoveries of new catalysts for the synthesis of relevant targets, such as pharmaceuticals. Recent advances in ligand synthesis using combinatorial methods have allowed the generation of a great diversity of catalysts. However, selection methods are few in number. We introduce a new selection method that focuses on the stability of catalytic intermediates measured by mass spectrometry. The stability of the intermediate relates inversely to the reactivity of the catalyst, which forms the basis of a catalyst-screening protocol in which less-abundant species represent the most-active catalysts, 'the survival of the weakest'. We demonstrate this concept in the palladium-catalysed allylic alkylation reaction using diphosphine and IndolPhos ligands and support our results with high-level density functional theory calculations.
authors.affiliation: Van 't Hoff Institute for Molecular Sciences, University of Amsterdam, Nieuwe Achtergracht 166, 1018 WV Amsterdam, The Netherlands.
authors.forename: Jeroen
authors.initials: J
authors.lastname: Wassenaar
authors.forename: Eveline
authors.initials: E
authors.lastname: Jansen
authors.forename: Willem-Jan
authors.initials: WJ
authors.lastname: van Zeist
authors.forename: F Matthias
authors.initials: FM
authors.lastname: Bickelhaupt
authors.forename: Maxime A
authors.initials: MA
authors.lastname: Siegler
authors.forename: Anthony L
authors.initials: AL
authors.lastname: Spek
authors.forename: Joost N H
authors.initials: JN
authors.lastname: Reek
mesh_terms: D000085:Acetates / Q000737:chemistry; D000478:Alkylation; D000498:Allyl Compounds / Q000737:chemistry; D002384:Catalysis; D008024:Ligands; D013058:Mass Spectrometry / Q000379:methods*; D008958:Models, Molecular; D015394:Molecular Structure; D010165:Palladium / Q000737:chemistry; D010720:Phosphines / Q000737:chemistry
chemical_list: D000085:Acetates; D000498:Allyl Compounds; D008024:Ligands; D010720:Phosphines; D010165:Palladium; C044646:phosphine