Because of their unusual acidity very strong base makes it possible to isomerize an internal acetylene to the less stable terminal isomer. Many chemical reactions may be understood in terms of localized bonds, but the special stability of conjugated systems requires considering delocalized orbitals or "resonance." Equilibrium constants, rates, and regiochemistry in systems involving allylic cations, anions, transition states, and free radicals demonstrate that allylic conjugation is worth about 13 kcal/mole.

Isoprenoid or terpene natural products, that seem to be made from isoprene (2-methylbutadiene), are formed by oligomerization of electrophilic isopentenyl pyrophosphate (IPP). Latex, the polymer of IPP, became commercially important when Charles Goodyear, a New Haven native, discovered how to vulcanize rubber. Statistical mechanics explains such curious properties of rubber as contraction upon heating when tightly stretched. Specific chemical treatment confers useful properties on a wide variety of polymers, including hair, synthetic rubber, and plastics.

Alkenes may be oxidized to diols by permanganate or by OsO4 catalysis. Metal catalysts provide orbitals that allow simultaneous formation of two bonds from metal to alkene or H2. Coupling such oxidative additions to reductive eliminations, provides a low-energy catalytic path for addition of H2 to an alkene. Such catalytic hydrogenation is often said to involve syn stereochemistry, but the primary literature shows that addition can be anti when allylic rearrangement occurs on the catalyst.

The formation of epoxides and the regiospecificity of their acid- and base-catalyzed ring openings underlines the importance of thinking carefully about how textbooks draw curved arrows and may sometimes read too much into fundamentally inadequate experimental data. The ozonolysis of alkenes begins with several 1,3-dipolar cycloadditions that can be understood in terms of matching HOMOs with LUMOs of the corresponding symmetry. The process continues with acetal hydrolysis and either reduction or oxidation to obtain the desired product. Mechanisms of these typical reactions are analyzed.

After drill on the mechanism of the pinacol rearrangement, this lecture applies molecular-orbital analysis to simultaneous electrophilic/nucleophilic attack by a single atom to form a three-membered ring from an alkene. These reactions provide drill in consistent use of the curved-arrow formalism for describing electron-pair shifts. Two alternative mechanisms for formation of cyclopropanes by the alkylzinc Simmons-Smith "carbenoid" reagent are proposed, and the one-step mechanism is supported by theory.

When electrophilic addition involves a localized carbocation intermediate, skeletal rearrangement sometimes occurs, but it can be avoided when both alkene carbons are involved in an unsymmetrical 3-center-2-electron bond, as in Markovnikov hydration via alkoxymercuration followed by reduction. Similarly a reagent that attacks both alkene carbons simultaneously by providing a nucleophilic component during electrophilic attack can avoid rearrangement, as in reactions that proceed via three-membered-ring halonium intermediates.

Substitution stabilizes alkenes, and addition of acids is thermodynamically favorable in acidic media.  Addition to alkenes can involve free-radical, metal-catalyzed, and stepwise electrophilic mechanisms, the last via a cation intermediate. Electrostatics can help position an attacking electrophile like H+, but bonding en route to Markovnikov addition requires orbital mixing to form the more stable cation.  Relative cation stability can be understood in terms of hyperconjugation, hybridization, and solvation or polarizability.

Bridged pentavalent carbon structures can be intermediates or transition states of cation rearrangement during SN1 reactions, and short-lived ion pairs explain net stereochemical inversion. The different perspectives of preparative organic chemists and mechanistic organic chemists on reaction yields are illustrated by a study designed to demonstrate that molecular rotation can be rate-limiting in viscous solvents. "Electrophilic" addition to alkenes is the reverse of E2 or E1 reaction, and its mechanisms can be studied by analogous techniques.

Preliminary X-ray analysis of molecules that have been designed to favor a carbon with five bonds seemed to suggest the possibility of a pentavalent intermediate in SN2 reactions, but further analysis of these structures showed just the opposite. Boron, however, can be pentavalent in such an environment.  E2, SN1 and E1 mechanisms compete with the SN2 reaction. Factors controlling E2 eliminations are illuminated by kinetic isotope effects, stereochemistry, and regiochemistry.

The nature of nucleophiles and leaving groups has strong influence on the rate of SN2 reactions. Generally a good nucleophile or strong base is a poor leaving group, but hydrogen-bonding solvents can alter nucleophile reactivity. Although amino and hydroxyl groups are poor leaving groups, they may be converted to groups that leave easily, even from bridgehead positions. Designing the preparation of a sugar analogue containing radioactive fluorine shows how understanding the SN2 mechanism enables PET scanning for medical imaging.