Stereochemistry of the Reaction Intermediates of Prolinol Ether Catalyzed Reactions Characterized by Vibrational Circular Dichroism Spectroscopy

Abstract

Spectroscopic characterizations of key reaction intermediates are often considered the final confirmation of a reaction mechanism. This proof‐of‐principle study showcases the application of vibrational circular dichroism (VCD) spectroscopy for the characterization of in situ generated reaction intermediates using the key intermediates of enamine catalysis of Jørgensen–Hayashi‐type prolinol ether catalysts as model system. By comparison of experimental and computed spectra, the enamines are shown to preferentially adopt an anti‐conformation with E‐configured C=C bond. For the parent prolinol catalyst, the structure and stereochemistry of the oxazolidine side product is determined as well. This study thus demonstrates that VCD spectra can provide insights into structural preferences of organocatalysts that utilize a covalent activation mechanism. Thereby it outlines new fields of applications for VCD spectroscopy and finally adds the technique to the toolbox of physical organic chemistry for in‐depth mechanistic studies.

Recent Advances in the Application of Vibrational Circular Dichroism Spectroscopy for the Characterization of Asymmetric Catalysts

“…(Reproduced from ref. [41] .). spectrum which indicates residual aldehyde, while the IR band of the mole water that is formed in the reaction is hidden under the intense and sharp band at 1650 cm -1 .…”

“…The different reactivities of 15a-c [40,42] allowed us to characterize the enamine intermediates 15a/b and the reaction towards oxazolidine 16 by VCD spectroscopy. [41] As representatives for the results of this investigation, the experimental and computed IR and VCD spectra of enamine 15a are shown in Figure 5. For sample preparation, a mixture of 14a and isovaleraldehyde was left for 15 minutes on the bench before recording the experimental spectra, which left ample time for 15a to form.…”

“…This side reaction proceeds rapidly for 15c , slowly for 15b and it is not detected for 15a . (Reproduced from ref …”

“…The numbers indicate band assignments, the asterisk marks a band of residual aldehyde. (Reproduced from ref …”

“…The different reactivities of 15a–c , allowed us to characterize the enamine intermediates 15a/b and the reaction towards oxazolidine 16 by VCD spectroscopy . As representatives for the results of this investigation, the experimental and computed IR and VCD spectra of enamine 15a are shown in Figure .…”