Conformational Analysis

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Conformational Analysis
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Ethane and Propane
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Relationship between DG and Keq and pKa
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Butane
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n-Butane Torsional Energy Profile
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Hierarchy of Eclipsing Interactions
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n-Butane Torsional Energy Profile
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Butane in Chair Form
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n-Pentane
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The Syn-Pentane Conformation
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The syn-Pentane Interaction - Consequences
Using our knowledge of acyclic conformational
analysis, we can predict the conformation found
in the crystal state of a bourgeanic acid
derivative.
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The syn-Pentane Interaction - Consequences
Using our knowledge of acyclic conformational
analysis, we can predict the conformation found
in the crystal state of a bourgeanic acid
derivative.
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The syn-Pentane Interaction - Consequences
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Acyclic Conformation Biological Affects
Evans, D. A. Bender, S. L. Morris, J. J. Am.
Chem. Soc. 1988, 110, 2506-2526.
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Acyclic Conformation Biological Affects
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Acyclic Conformation Biological Affects
Overlay of the two X-ray structures
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Butane Vs. 1-Butene
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Allylic Strain A1,2-strain
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Allylic Strain A1,3-Strain
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Useful Destabilizing Interactions to Remember
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A1,2-Strain in Chiral Systems
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A1,3-Strain in Chiral Systems
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Discodermolide

• Isolated in 1990 from the Caribbean marine sponge
  Discodermia dissoluta.
• 434 g of sponge yielded 7 mg discodermolide
  (0.002 by weight).
• Discodermolide has immunosuppresive, antifungal
  and antitumor activity.
• Has been synthesized by Schreiber, Smith,
  Paterson, Marshall, and Myles.
• Review Paterson, I. Florence, G. J. Eur. J.
  Org. Chem. 2003, 2193.

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Allylic Strain Amide Conformation
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Allylic Strain Amide Conformation
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Allylic Strain Amide Conformation
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Conformational Analysis of Cyclic Systems
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Cyclopropane
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Cyclobutane
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Cyclopentane
n Two lowest energy conformations of cyclopentane
(10 envelope and 10 half chair conformations)
differ by only 0.5 kcal/mol. They are in rapid
conformational flux (pseudorotation) which causes
the molecule to appear to have a single
out-of-plane atom "bulge" which rotates about
the ring. n Since there is no "natural"
conformation of cyclopentane, the ring conforms
to minimize interactions of any substituents
present.
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Methylenecyclopentane and Cyclopentane
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Cyclohexane Energy Profile
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Monosubstituted Cyclohexanes A Values
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Monosubstituted Cyclohexanes A Values
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Vicinal Substitution
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Vicinal Substitution
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Geminal Substitution
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Geminal Substitution
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Cycloheptane
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Cyclooctane
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Cyclooctane
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Polysubstituted Cyclohexane A-Values
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Conformational Analysis of Bicyclic Systems
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Bicyclic Systems
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Bicyclic Systems