Alicyclic Chemistry: Ring Formation and Stereoelectronics

Flashcards covering ring contraction mechanisms, Baldwin's rules, various named cyclisation reactions, and strategies for making medium and large rings.

$\beta$-Lactam ring

The key structural feature of the penicillin class of antibiotics that imitates the $D-Ala$ residue to irreversibly inhibit bacterial cell wall synthesis by covalently binding to the enzyme active site.

Favorskii rearrangement

A ring contraction reaction where a cyclic $ext{\alpha}-halo$ ketone is treated with base, resulting in an ester of the contracted ring after bond migration.

Wolff rearrangement

A ring contraction reaction where a cyclic $ext{\alpha}-diazo$ ketone is irradiated with light to form a carbene that undergoes rearrangement to form a smaller ring.

Baldwin's Rules (endo-trig)

Guidelines for cyclisation favorability stating that $6$- and $7-endo-trig$ are favoured, but $5-endo-trig$ is disfavoured.

Nazarov cyclisation

A reaction used to form cyclopentenones from divinyl ketones using a Lewis Acid.

Dieckmann reaction

The intramolecular version of the Claisen condensation, commonly used for ring formation.

Thorpe-Ziegler condensation

A reaction involving the cyclisation of a dinitrile, similar to the Dieckmann reaction.

Transannular strain

A form of strain that causes medium-ring formation to suffer from high $\Delta H^{\ddagger}$, hindering the reaction.

Effective Molarity (EM)

The ratio defined as $EM = \frac{k_{intramolecular}}{k_{intermolecular}}$, representing the relative rate constants of cyclisation vs. polymerization.

High Dilution

A reaction strategy typically performed at $\sim 5\,mM$ or below to minimize intermolecular reactions and favour the cyclic product.

Ring-Closing Olefin Metathesis (RCM)

A reaction where two alkene groups 'switch partners' to produce ethene and an internal double bond, forming a ring via transition metal carbene catalysts.

Demjanov ring expansion

A reaction that increases the size of an alicyclic ring.

Acyloin reaction

A radical-radical dimerisation reaction where an ester is reduced using sodium metal, resulting in an \text{\alpha}-hydroxy-ketone after workup.

McMurry reaction

A radical-radical dimerisation of ketones promoted by titanium (0) where carbonyl groups are reduced and deoxygenated at the metal surface to form cycloalkenes.

Chemical Template

As defined by Prof Daryl Busch: an assembly of atoms that organizes a substrate's geometry through interactions like hydrogen bonding or metal coordination to achieve a particular linking of atoms.

Crown ethers

Macrocycles, such as dibenzo-18-crown-6, whose formation is templated by alkali metal cations that interact with oxygen lone pairs to bring end groups close together for cyclisation.