Transition State Modeling and Catalyst Design for Hydrogen Bond-Stabilized Enolate Formation
Citations Over TimeTop 23% of 2005 papers
Abstract
[reaction: see text] A catalyst for enolate formation was designed that incorporates an amine base along with a thiourea to bind to the oxygen atom of the substrate and enolate through hydrogen bonding. A computational model of the transition state was developed in which the thiourea (modeled initially as a urea) and amine were separate molecules. This model and models incorporating one or two methanol molecules in place of the urea showed an out-of-plane hydrogen bond, apparently to the carbonyl pi-bond, in addition to an in-plane hydrogen bond to an unshared electron pair. In contrast, optimized complexes of the ketone and the fully formed enolate showed only in-plane hydrogen bonding. The transition state model with the urea and amine was used to define a database search with the computer program CAVEAT to identify structures suitable for linking the amine and urea/thiourea moieties in the transition state. On the basis of a group of structures identified from this search, a flexible but conformationally biased linker was designed to connect the two catalytic moieties. The molecule having the amine and thiourea moieties connected by this linker was synthesized and was shown to catalyze proton exchange between methanol and deuterated acetone. The catalyst was about 5-fold more efficient than the amine and thiourea as separate molecules and relative to a similar but less conformationally biased catalyst.
Related Papers
- → Infrared study of the interactions between the different kinds of water molecules present in sepiolite(1975)36 cited
- → Water molecules which apparently accept no hydrogen bonds are systematically involved in C—H.O interactions(1995)32 cited
- → Pyrimidin-2-amine–1-phenylcyclopentane-1-carboxylic acid (1/1)(2011)2 cited
- → Infrared Spectra of Thiourea and its Inclusion Compounds. II. Spectra of Guest Molecules(1962)1 cited
- → Effect of the orientation of the water molecules in the system of hydrogen bonds in the crystal hydrate of m-bromo-N?-(5-nitrofurylidene)benzohydrazide on its sensitivity to light(1990)