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Computationally‐Guided Investigation of Dual Amine/pi Lewis Acid Catalysts for Direct Additions of Aldehydes and Ketones to Unactivated Alkenes and Alkynes
Author(s) -
Greve Eric,
Porter Jacob D.,
Dockendorff Chris
Publication year - 2020
Publication title -
chemistryselect
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.437
H-Index - 34
ISSN - 2365-6549
DOI - 10.1002/slct.202001840
Subject(s) - chemistry , alkyne , catalysis , hydroamination , intramolecular force , ketone , lewis acids and bases , alkene , enamine , oxazoline , pyridine , medicinal chemistry , aldehyde , hydroacylation , organic chemistry
Dual amine/pi Lewis acid catalyst systems have been reported for intramolecular direct additions of aldehydes/ketones to unactivated alkynes and occasionally alkenes, but related intermolecular reactions are rare and not presently of significant synthetic utility, likely due to undesired coordination of enamine intermediates to the metal catalyst. We reasoned that bulky metal ligands and bulky amine catalysts could minimize catalyst poisoning and could facilitate certain examples of direct intermolecular additions of aldehydes/ketones to alkenes/alkynes. Density Functional Theory (DFT) calculations were performed that suggested that pyridine‐2,6‐bis(oxazoline) (PyBOX)‐Pt(II) catalysts for alkene/alkyne activation could be combined with MacMillan's imidazolidinone organocatalyst for aldehyde/ketone activation to facilitate desirable C−C bond formations, and certain reactions were calculated to be more exergonic than catalyst poisoning pathways. Consistent with the calculations, preformed enamines generated from the MacMillan imidazolidinone did not displace ethylene from a biscationic ( t ‐Bu)PyBOX‐Pt 2+ complex. The desired intermolecular C−C bond formation was not observed under several different conditions, but this novel catalytic system facilitated an intramolecular C−C bond formation (Conia‐ene type reaction) with a formyl alkyne substrate.