Molecular Modeling as an Aid to Understanding Stereoselectivity

Document Type

Article

Publication Date

1999

Disciplines

Chemistry | Organic Chemistry | Physical Sciences and Mathematics

Abstract

With the introduction of hydride reducing agents, organic chemists were able to search for an explanation for the peculiar reducing pattern of substituted cyclohexanones. Through the 1960s and 1970s, steric and then electronic arguments were marshaled to explain the cis/trans ratio of products. We have used this experiment to introduce our students to the importance of conformational analysis and the power of orbital analysis. Students use a molecular mechanics calculation program within Spartan to determine the Boltzmann distribution of conformers of 2-, 3-, and 4-methylcyclohexanone. On the basis of these data, they predict the face of the carbonyl most susceptible to attack by hydride. Reduction of the respective ketone with sodium borohydride affords a cis/trans mixture of alcohols, which is analyzed by GC-MS and IR. Calculation of the LUMO of the starting material is then used to explain the experimental result. Students are able to see the antisymmetry of the LUMO at the carbonyl carbon and determine the absolute value of the LUMO at the surface. This interactive use of computer modeling is an excellent way for students to make sense of the experimental results. The conformational analysis calculations were also successfully completed with Hyperchem and CACHe molecular modeling packages. The calculation and visualization of the LUMO, however, was not as compelling with these systems.

Comments

DOI: 10.1021/ed076p985

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