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IA. Conformational Analysis

Boger Notes: p. 1 - 16 (Chapter I)

Problem of the Day: Chem. Commun. 1997, 1855

- Explain the stereoselectivity- Draw two chair conformations of 3; vicinal 1H J-analysis indicatesthat the SPh substituent is equatorial; is this supported by an analysisof the relative energies of the two chair conformers?

I. Basic Principles

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Definitions

Constitution: defines the connectivity of atoms in a molecule of a givencomposition. E.g. C2H6O and C3H8O have different composition;CH3-CH2-OH and CH3-O-CH3: have the same number and kind ofatoms, but different connectivity - they are constitutional isomers.

Constitutional isomers have different physical and chemical properties.

Special cases: tautomers (rapidly equilibrating constitutional isomers

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Structure Analysis by Computational Methods: ORD Calculations

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IA. Conformational Analysis - Continued

Problem of the Day: J. Am. Chem. Soc. 1989, 2599

- Propose relative configurations for 2-6- What is the name of the conversion of 4 to 6 via 5?- What is the name of the natural product that contains the decalin 6 as asubstructure? What is it used for, and who discovered it?

I. Basic Principles

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The anomeric effect

Fifer, N. L.; White, J. M., "Determining the σ-donor ability of the cyclopropane C-C bond."Organic & Biomolecular Chemistry 2005, 3, 1776-1780.

The anomeric effect is an n->σ* phenomenon.The presence of good donor orbitals vicinal and antiperiplanar to the C-Obond results in a strong response of the C-OR distance to the electrondemand of OR. This reflects increased stabilization of the cation part of thevalence bond form C+ -OR.

Hyperconjugation (or σ-π conjugation) is a particularly important type ofdonor-acceptor interaction between a filled σ-bonding orbital and an electrondeficient orbital such as a carbocation p-orbital.A related effect can be attributed to silicon groups, double bonds, andcyclopropanes (σ->σ* interaction).

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Electrostatic (dipole) effects are also important:

- Wipf, P.; Kim, Y. J. Am. Chem. Soc. 1994, 116, 11678. Wipf, P.; Jung, J.-K.Angew. Chem. Int. Ed. Engl. 1997, 36, 764-7. Wipf, P.; Jung, J.-K., "Nucleophilicadditions to 4,4-disubstituted 2,5-cyclohexadienones: Can dipole-effects controlfacial selectivity?" Chem. Rev. 1999, 99, 1469.

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Calculation of the component of the molecular dipole moment parallel tothe π-plane, µ⊥, by fast semiempirical MO methods results in astraightforward linear relationship with the logarithm of the experimentalratio of α- and β-attack of organometallic reagents. This correlationallows the quantitative prediction of experimental 1,4-diastereoselectivities. Our conclusion is that electrostatic effectsdetermine the face-selectivity of nucleophilic carbonyl additions insterically unhindered cyclohexadienones and naphthoquinones.

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The results can be explained in terms of Felkin’s torsional strainmodel plus steric interactions (for cyclohexanone).

For an analysis based on π-facial differences in the LUMO(ground state) that rejects the Cieplak (transition statehyperconjugative stabilization) model, see: Tomoda, S.; Zhang,J.; Kaneno, D.; Segi, M.; Zhou, A., "Reversal of π-facialdiastereoselection in the hydride reduction of selenanones.Further application of the exterior frontier orbital extensionmodel." Tetrahedron Lett. 2000, 41, 4597-4601.

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