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STEREOSELECTIVITY AND MECHANISM
Prof. H.L. Anderson
Michaelmas Term – Third Year (6 lectures)
Core IB Organic Chemistry
1) Conformational Analysis and Stereoelectronics: stereoelectronic
control of conformation in molecules such as CH3OCH2F,
CH3OCH2OCH3, FCH2CH2F,
CH3SSCH3, C2H6,
CH3CO2CH3; stereoelectronic
reactivity effects; other effects dictating the conformation
of flexible molecules: 1,3-allylic strain, syn-pentane
interactions, hexa-alkyl benzenes (and if time permits: hydrogen-bonding,
aromatic-aromatic interactions).
2) Stereoeselctivity in Addition to C=O Bonds: facial
selectivity in addition to acyclic chiral aldehydes and ketones:
Cram’s rule, Felkin-Anh model; exceptions: electronegative
groups and chelation control; aldol reactions via chair transitions
states; addition to cyclohexanones with large and small nucleophiles,
torsional model; asymmetric reduction of achiral ketones.
3) Stereoeselctivity in Addition to C=C Bonds: Woodward
and Prévost reactions; chelation-control of facial
selectivity of Simmons-Smith cyclopropanation e.g. of 3-hydroxycyclopentene;
hydrogen-bonding control of facial selectivity of epoxidation
in cyclic and acyclic allyl alcohols; epoxidation and alkylation
of allyl silanes; electrophile-initiated cyclisations: iodolactonisation,
ene-cyclisations, squalene-type cyclisations; asymmetric synthesis:
Sharpless epoxidation, Jacobsen epoxidation, Sharpless dihydroxylation
(these last three reactions will be mentioned briefly without
mechanistic discussion).
4) Hammett Relationships: the Hammett equation as
an example of a linear free energy relationship; examples
of substituent constants (s) and
reaction constants (r); through-conjugation
(sp+); nonlinear
Hammett plots: (a) due to change in mechanism: ArCOCl hydrolysis,
norbornyl homoallylic carbocations, and (b) due to change
in rate determining step: intramolecular Friedel-Crafts alkylation,
imine formation.
5) Kinetic Isotope Effects and Acid/Base Catalysis:
primary kinetic isotope effects, e.g. in radical substitution;
secondary kinetic isotope effects (a) due to changes in hybridisation,
and (b) due to hyperconjugation; solvent isotope effects;
specific acid/base catalysis; general acid/base catalysis;
pH vs. rate profiles e.g. for enol ether hydrolysis, epoxide
hydrolysis, aspirin hydrolysis and imine formation.
6) Worked examples of exam questions relating to the above
five lectures.
Please do questions on pages 8–13 of the handout before
coming to this lecture.
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