Abstract
Bifunctional catalyst systems for the direct addition of ketones to unactivated alkenes/alkynes
were designed and modeled by density functional theory (DFT). The designed catalysts
possess bidentate ligands suitable for binding of pi-acidic group 10 metals capable
of activating alkenes/alkynes, and a tethered organocatalyst amine to activate the
ketone via formation of a nucleophilic enamine intermediate. The structures of the
designed catalysts before and after C–C bond formation were optimized using DFT, and
reaction steps involving group 10 metals were predicted to be significantly exergonic.
A novel oxazoline precatalyst with a tethered amine separated by a meta-substituted
benzene spacer was synthesized via a 10-step sequence that includes a key regioselective
epoxide ring-opening step. It was combined with group 10 metal salts, including cationic
Pd(II) and Pt(II), and screened for the direct addition of ketones to several alkenes
and an internal alkyne. 1 H NMR studies suggest that catalyst-catalyst interactions with this system via amine–metal
coordination may preclude the desired addition reactions. The catalyst design approach
disclosed here, and the promising calculations obtained with square planar group 10
metals, light a path for the discovery of novel bifunctional catalysts for C–C bond
formation.
Key words alkylation - alkene complexes - platinum - bifunctional catalysis - organocatalysis
- ketones - DFT - catalyst design
