This proposal describes a conceptually new approach to asymmetric catalyst design. Traditional asymmetric catalysts rely on chiral ancillary ligands coordinated to the metal (inner sphere) to provide stereocontrol. We propose to influence selectivity through rational modification of a catalyst's outer sphere, a strategy inspired by enzymatic mechanisms for controlling catalysis. Molecular imprinting of square planar platinum (II) complexes into rigid and porous organic polymers, followed by selective removal of a noncrosslinked chiral ligand from the modular template, reveals a kinetically robust chiral cavity that is intimately assoicated with the reactive coordination sites on the catalytic center. This cavity provides the outer-sphere environment for selectivity control, and is a natural mix of molecular recognition and asymmetric catalysis. The goals of this proposal are to: 1) Fundamentally understand outer-sphere stereocontrol. Can the outer-sphere be harnessed to control reaction selectivities? Enzyme analogies and preliminary data suggest it can. 2) Synthesize selective noble metal asymmetric catalysts that function via a combination of inner- and outer-sphere stereocontrol elements. Molecular imprinting will yield novel catalysts for the enantioselective hydrogenation of alkenes and ketones, and the enantioselective sp2-sp2 and sp2-sp3 cross coupling reactions. Built into the imprinting strategy is the flexibility to: a) orient functional groups within the associated cavity for transition state (pre)organization, and b) modify the phosphine ligand to access novel electron rich catalysts. Our targeted reactions are important for the synthesis of new chiral feedstocks that will eventually reduce our reliability on the chiral pool. Moreover, our approach to generating enantioselective catalysts utilizes inexpensive achiral diphosphines and results in heterogenized catalysts there are valuable in medicinal and process research as well as bulk fine chemical synthesis. Increased commercial availability of chiral precursors will aid in drug discovery and pharmaceutical process synthesis.
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