Computationally‐Guided Investigation of Dual Amine/pi Lewis Acid Catalysts for Direct Additions of Aldehydes and Ketones to Unactivated Alkenes and Alkynes. Issue 28 (24th July 2020)

• Record Type: Journal Article
• Authors: Greve, Eric; Porter, Jacob D.; Dockendorff, Chris
• Is Part Of: ChemistrySelect. Volume 5:Issue 28(2020)
• Page Start: 8405
• Page End: 8414
• Publication Date: 2020-07-24
• Subjects: Conia-ene -- density functional theory -- dual catalysis -- organocatalysis -- pi Lewis acid; Chemistry -- Periodicals; 540.5
• DOI: 10.1002/slct.202001840
• Languages: English
• ISSNs: 2365-6549

Abstract

Abstract: 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. Abstract : Density functional theory calculations were performed to identify dual amine/pi Lewis acid catalyst systems that could promote challenging C−C bond formations. Calculations of a pyridine‐bis(oxazoline)‐Pt(II) catalyst combined with a bulky organocatalyst suggested that alkenes and alkynes could be activated for outer‐sphere attack without metal/organocatalyst or metal/enamine poisoning. Reaction screening confirmed that this novel catalyst system facilitated an intramolecular addition (Conia‐ene type reaction) with a formyl alkyne substrate.