How Do Substrates Bind to a Bifunctional Thiourea Catalyst? A Vibrational CD Study on Carboxylic Acid Binding

Area of Science:

• Chemistry
• Spectroscopy
• Computational Chemistry

Background:

• Understanding asymmetric catalyst active conformations is crucial for stereoinductive power.
• Spectroscopic access to these conformations is often limited.
• Takemoto's bifunctional thiourea serves as a model system.

Purpose of the Study:

• To demonstrate VCD spectroscopy's capability in characterizing catalyst conformational preferences.
• To analyze catalyst-reactant interactions, specifically carboxylic acid binding.
• To identify limitations in computational methods for predicting solution-phase structures.

Main Methods:

• Vibrational Circular Dichroism (VCD) spectroscopy.
• Infrared (IR) spectroscopy.
• Computationally guided spectral analysis using Density Functional Theory (DFT).

Main Results:

• VCD spectroscopy successfully characterized conformational preferences of the thiourea catalyst, both free and bound to carboxylic acids.
• The binding orientation of carboxylic acids was readily determined.
• Characteristic marker bands unique to VCD spectra of catalyst/acid mixtures were identified.
• DFT functional M06-2X showed inaccuracies in predicting molecular cluster structures due to overestimation of non-covalent interactions.

Conclusions:

• VCD spectroscopy is a powerful tool for characterizing catalyst conformations and binding modes.
• VCD can identify and help correct computational mispredictions of solution-phase structures.
• The study highlights the importance of considering solvent effects in computational chemistry.