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A neighbouring tertiary amine displaces a leaving group to form a three-membered ammonium ring; attack at the original ring carbon cleaves its old C–N bond and incorporates the side-chain carbon into an expanded nitrogen ring.

One valid asymmetric route uses N-Boc-(R)-proline as a chiral starting material. Convert its acid to the Weinreb amide with N,O-dimethylhydroxylamine and a coupling reagent such as EDC, then add phenylmagnesium bromide at low temperature. chelation of the magnesium tetrahedral intermediate prevents a second addition; aqueous workup releases the phenyl ketone. Reduce it with sodium borohydride, separate the resulting alcohol diastereomers, and retain the one with $R$ configuration at both pyrrolidine C2 and the benzylic carbinol. This is an asymmetric synthesis through a pre-existing enantiopure centre, even though the final reduction need not be perfectly diastereoselective. If the other protected alcohol is isolated, Mitsunobu esterification with a carboxylic acid followed by ester hydrolysis inverts just the carbinol centre. Keeping nitrogen Boc-protected during that inversion avoids neighbouring-amine participation. Mild Boc removal followed by reductive benzylation with benzaldehyde and sodium triacetoxyborohydride gives D, the $(R,R)$ amino alcohol. Use conditions that avoid epimerizing the amino ketone.

For ring expansion, activate D's alcohol with methanesulfonyl chloride and a tertiary amine base. Its own tertiary nitrogen attacks the benzylic carbon from the back, displacing mesylate with inversion and making a fused aziridinium ion. Acetate, supplied as a soluble acetate salt, attacks the original pyrrolidine C2 from the opposite face and breaks the old C2–N bond. The new N–benzylic-C bond is retained, incorporating that side-chain carbon into the six-membered ring. Inversion at the two successively attacked carbons gives the cis acetate/phenyl piperidine E in the displayed orientation. Attack at the benzylic carbon instead would simply open the three-membered ion back to a five-membered-ring derivative; specifying the attacked carbon is the crucial regiochemical step.

Each primary amine arm of 2 condenses with one aldehyde 1, eliminating three waters overall and forming a tripodal tris(pyridylimine) ligand $L$. The three imine nitrogens and the three adjacent pyridine nitrogens chelate one Fe(II), giving $[\mathrm{Fe}L{]}^{2+}$, with three outward-facing terminal pyridines still free. The central tertiary amine is the tethering apex, not a seventh donor in the six-coordinate model.

The Fe coordination is approximately octahedral and is propeller-chiral: three bidentate chelates can have $\Delta$ or $\Lambda$ configuration. Achiral starting components and conditions give a racemic population unless a separate resolving influence is introduced. imine condensation and metal coordination cooperate in subcomponent self-assembly; the metal template selects the convergent ligand arrangement.

methyl fluorosulfonate alkylates the tertiary isoxazolidine nitrogen, giving a quaternary N-methyl ammonium salt; the methyl remains attached to nitrogen in F. hydride from lithium aluminium hydride then cleaves the N–O bond, releasing the corresponding oxygen as an aluminium-bound alkoxide while restoring neutral tertiary amine nitrogen. Aqueous workup protonates the alkoxide to give the alcohol.

Thus the C–O bond made in the cycloaddition survives as the alcohol-bearing C–O bond, and the formaldehyde-derived methylene survives as the extra carbon between nitrogen and the carbon framework. The N–O bond is the one removed. N-methylation followed by reductive N–O cleavage gives the bridged amino alcohol F without requiring cleavage of its newly formed C–C bond or hydrogenation of a nonexistent residual alkene.

One design is an anthracene–methylene–aza-15-crown-5 sensor, with the tertiary amine of the aza-crown linked through $\mathrm{C}{\mathrm{H}}_2$ to anthracene. The crown supplies the sodium-binding oxygen/nitrogen cavity, the amine supplies an electron donor and anthracene supplies the fluorophore. A sufficiently rigid sodium-sized cryptand could improve discrimination further.

Without a bound cation, photoinduced electron transfer from the amine can quench excited anthracene. sodium coordination lowers the electron-donating ability of that lone pair, suppressing this quenching route and increasing fluorescence. The methylene spacer allows electronic communication by electron transfer while limiting direct conjugation between the binding site and fluorophore.

A cavity appropriate to sodium is preferable to an 18-crown-6-like potassium-sized cavity. Selectivity must be tested, not inferred perfectly from cavity size. Potassium binding, including possible sandwich complexes of flexible crowns, can still compete. At the intended concentrations the design should satisfy $K_{\mathrm{Na}}[\mathrm{N}{\mathrm{a}}^{+}]\gg K_{\mathrm{K}}[{\mathrm{K}}^{+}]$ and should give a fluorescence change on sodium binding. Rigidity, cavity size and suppression of competing stoichiometries are useful design controls. fluorescence calibration in the actual potassium-containing solvent establishes the usable detection range.