Quantifying the Strengths of Dual-Hydrogen-Bond Donors as Organocatalysts
Abstract
Despite the importance of dual-hydrogen-bonding organocatalysis in modern synthetic organic chemistry, the optimal hydrogen-bond donors for various common functional groups remain unknown. Additionally, the relationship between the ability of a given organocatalyst to form strong hydrogen bonds with the substrate and the resulting catalytic activity is unclear. These relationships can be studied with density functional theory (DFT) to quantify the performance of dual-hydrogen-bonding organocatalysts in model reactions. Complexes of 25 dual-hydrogen- bonding organocatalysts with methyl vinyl ketone (MVK) and nitroethylene (NE) were studied, along with the transition states for the corresponding organocatalyzed Diels-Alder cycloaddition of MVK with cyclopentadiene (CPD) and the Friedel-Crafts alkylation of NE with indole. Overall, the results reveal key relationships between catalyst binding energy and catalytic efficacy, and provide quantitative information about the hydrogen bond strengths and transition state lowering ability of a wide range of model catalysts for these two reactions. These data will help design more effective dual-hydrogen-bonding catalysts for the synthesis of complex chiral molecules and natural products.
Citation
Shea, Jacqueline Ruth (2016). Quantifying the Strengths of Dual-Hydrogen-Bond Donors as Organocatalysts. Undergraduate Research Scholars Program. Available electronically from https : / /hdl .handle .net /1969 .1 /188490.