title: Three-component reaction discovery enabled by mass spectrometry of self-assembled monolayers.
abstract: Multicomponent reactions are employed extensively in many areas of organic chemistry. Despite significant progress, the discovery of such enabling transformations remains challenging. Here, we present the development of a parallel, label-free reaction-discovery platform that can be used in the identification of new multicomponent transformations. Our approach is based on parallel mass spectrometric screening of interfacial chemical reactions on arrays of self-assembled monolayers. This strategy enabled the identification of a simple organic phosphine that can catalyse a previously unknown condensation of siloxyalkynes, aldehydes and amines to produce 3-hydroxyamides with high efficiency and diastereoselectivity. The reaction was further optimized using solution-phase methods.
authors.affiliation: Chicago Tri-Institutional Center for Chemical Methods and Library Development, Department of Chemistry, University of Chicago, Chicago, Illinois 60637, USA.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Montavon
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Jaime R
authors.initials: JR
authors.lastname: Cabrera-Pardo
authors.forename: Milan
authors.initials: M
authors.lastname: Mrksich
authors.forename: Sergey A
authors.initials: SA
authors.lastname: Kozmin
mesh_terms: D000447:Aldehydes / Q000737:chemistry; D000577:Amides / Q000737:chemistry; D000588:Amines / Q000737:chemistry; D002384:Catalysis; D020650:Combinatorial Chemistry Techniques; D006046:Gold / Q000737:chemistry; D013058:Mass Spectrometry; D008958:Models, Molecular; D010720:Phosphines / Q000737:chemistry; D012833:Siloxanes / Q000737:chemistry; D013440:Sulfides / Q000737:chemistry
chemical_list: D000447:Aldehydes; D000577:Amides; D000588:Amines; D010720:Phosphines; D012833:Siloxanes; D013440:Sulfides; D006046:Gold; C044646:phosphine