Lecture Notes 04 - Conformational Analysis 1

D. A. Evans, G. Lalic

Chem 530A Question of the day: Provide a 3D drawing of the following molecules:

Chemistry 530A

H3C

H3C CH3 CH3

Advanced Organic Chemistry

H3C CH3 CH3 CH3

Lecture notes #4

Conformational Analysis of Acyclic Compounds Conformation of Alkanes Conformation of Alkenes Allylic Strain Dougherty, "Modern Physical Organic Chemistry", page 92-100 Hoffmann, R. W. "Allylic 1,3-Strain as a Controlling Factor in Stereoselective Transformations." Chem. Rev. 1989, 89, 1841. (pdf) Goodman, L. “Hyperconjugation not steric repulsion leads to the staggered structure of ethane.” Nature 2001, 411, 565. (pdf) Baerends, E. J. "The Case for Steric Repulsion Causing the Staggered Conformation of Ethane." Angew. Chem. Int. Ed. 2003, 42, 4183. (pdf)

CH3 CH3

Weinhold, F. Nature 2001, 411, 539: “A new twist on molecular shape”

Preference of difluoroethane for a gauche conformer is called gauche-effect. Goodman, L. J. Phys. Chem. A 2005, 109, 1223‐1229 Wolfe, S. Acc. Chem. Res. 1972, 5, 102‐111

Gauche interaction Two methyl groups with dihedral angle of 60 degrees have a steric interaction that costs 0.8 kcal/ mol. This is general type of interaction similar to the eclipsing interaction and whenever possible will try to avid it. When substituents are bigger the interaction is worth more.

G. Lalic

Chem 530A

1. Provide a drawing of the most stable conformation of the following molecules.

4. Provide an explanation for the observation that the trans isomer is more stable, and provide a 3D drawing of the most stable conformer of that isomer.

H3C

H3C CH3 CH3

CH3 CH3

H3C CH3 CH3 CH3

2. Draw a 3D structure of the boxed portion of Bleomycin 5. The following structure is a partial structure of Discodermolide (C12‐C15). Please provide a 3D drawing of the most stable conformation. For the purpose of this question treat the R groups as large achiral groups.

3. Draw a 3D structure of the following two molecules.