|Selectivity Control in Enantionselective Hydroformylation |
Chemistry and Chemical Biology
|Clark Landis, University of Wisconsin-Madison|
11:00 AM, Chem-WL Aud
Catalytic hydroformylation is a commodity-scale transformation that has been practiced for more than thirty years. Current applications account for approximately $17 billion pounds of product per year. Much of the appeal of hydroformylation derives from its simplicity: two gaseous reactants (CO and H2) react with alkene in the presence of rhodium or cobalt catalysts to exothermically produce aldehydes with perfect atom economy. Commodity-scale applications favor hydroformylation of terminal alkenes to give linear aldehydes. A potent, but unrealized, application of hydroformylation is the enantioselective synthesis of branched aldehydes from terminal or internal alkenes. Our approach to creating effective enantioselective hydroformylation processes spans the design of new ligands, the development of new synthetic pathways to chiral ligands, exploration of the scope of alkene substrates and the empirical "rules" that predict selectivity, and detailed mechanistic studies of the origin of selectivity. Modern hydroformylation catalysts based on rhodium complexes of enantiopure bis-3,4-diazaphospholane ligands exhibit practical rates (ca. 5 turnovers/s) and selectivities (branched:linear ratios that can exceed 100:1 and enantiomeric excesses as high as 98%). Interestingly, the selectivity of aryl alkene hydroformylation exhibits pronounced pressure effects. Deuterium-labeling and kinetic studies reveal the origin of pressure effects and provide a general kinetic model for understanding selectivity.