| Molecular Models of Reactants and Products of an Asymmetric Synthesis of a Chiral Carboxylic Acid
Our JCE Featured Molecules for this month come from the paper by Thomas E. Smith, David P. Richardson, George A. Truran, Katherine Belecki, and Megumi Onishi (1). The authors describe the use of a chiral auxiliary, 4-benzyl-2-oxazolidinone, in the synthesis of a chiral carboxylic acid. The majority of the molecules used in the experiment, together with several of the pharmaceuticals mentioned in the paper, have been added to our molecule collection. In many instances multiple enantiomeric and diastereomeric forms of the molecules have been included.
This experiment could easily be extended to incorporate various aspects of computation for use in an advanced organic or integrated laboratory. Here are some possible exercises using the R and S forms of the 4-benzyl-2-oxazolidinone as the authors point out that both forms are available commercially. Calculation of the optimized structures and energies of the enantiomers at the HF/631-G(d) level using Gaussian03 (2) produces the results shown in Table 1.
Table 1. Calculation of the Optimized Structures and Energies of the Enantiomers of 4-Benzyl-2-oxazolidinonea
| |
R Form Single Point Calculation |
S Form Single Point Calculation |
|
Calculation Type |
SP |
SP |
Calculation Method |
RHF |
RHF |
Basis Set |
6-31G(D) |
6-31G(D) |
Charge |
0 |
0 |
Spin |
singlet |
singlet |
Total Energy |
-589.29383182 a.u. |
-589.29383182 a.u. |
RMS Gradient Norm |
0.0000000 a.u. |
0.0000000 a.u. |
Dipole Moment |
6.0110 D |
6.0110 D |
aDone at the Hf/631-G(D) level using Gaussian 03 (2).
Evaluation of the vibrational frequencies results in no imaginary frequencies and the 66 real frequencies are identical for the two forms. Examination of the computed IR spectra also shows them to be identical. Additionally, the Raman and NMR spectra can be calculated for the enantiomers and compared to experimental values and spectral patterns. A tool that is becoming increasingly important for assigning absolute configuration is vibrational circular dichroism (VCD). Although the vibrational spectra of an enantiomeric pair are identical, the VCD spectra show opposite signs, as shown in Figure 1.
 
Figure 1. Vibrational spectra of the R and S forms of 4-benzyl-2-oxazolidinone are identical, but the VCD spectra show opposite signs.
One can imagine a synthesis, using an unknown enantiomer of the chiral auxiliary, followed by calculations of the electronic and vibrational properties of all of the intermediates and the product, and determination of absolute configuration of reactants and products by comparison of experimental and computed VCD spectra.
Using a viewer capable of displaying two molecules that can be moved independently, students could more easily visualize the origin of the enantiomeric preference in the reaction between the chelated enolate and allyl iodide.
Literature Cited
- Smith, T. E.; Richardson, D. P.; Truran, G. A.; Belecki, K.; Onish, M. J. Chem. Educ. 2008, 85, 695–697.
- Frisch, M. J. et al. GAUSSIAN 03, Revision C.02; Gaussian, Inc.: Wallingford, CT, 2004.
Fully manipulable versions of all this month's molecules and other molecules are available at the JCE Digital Library Web site. |
