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Formation of a carbon–carbon bond at an anomeric carbon. In electrophilic aromatic substitution on a suitable heteroarene, carbon attack on an activated glycosyl donor is followed by deprotonation to restore aromaticity.

electrophilic aromatic substitution that installs an alkyl group on an aromatic ring.

Intramolecular electrophilic aromatic substitution that closes a carbon ring. Tether geometry and arene substitution control the accessible site and stereochemistry.

Treat the reacting carbon skeletons as an activated glycosyl donor and a 3-substituted indole. The new linkage is an anomeric-carbon–indole-C2 carbon–carbon bond, not a bond to indole nitrogen. A plausible purely chemical pathway is a dissociative electrophilic aromatic substitution:

The drawn donor and product have opposite anomeric faces: the anomeric leaving group is on the same face as the hydroxymethyl substituent, while the new carbon substituent is on the opposite face. Thus the target has net inversion at the anomeric carbon. A tight ion pair with the departing group shielding its original face can rationalize opposite-face capture in this proposed pathway. A freely solvated planar oxocarbenium ion would not by itself guarantee exclusive inversion; competing faces, hydrolysis and other products remain possible without an experimentally specified chemical promoter. This is a plausible non-enzymatic mechanism, not a claim that the uncatalysed reaction is rapid or clean in neutral water.

Number the ring with chlorine at C1 and the methylsulfonyl group at C4. The new nitro group is at C2, equivalently C6 by the starting ring's symmetry: the product is 1-chloro-2-nitro-4-(methylsulfonyl)benzene. Both substituents favour this site. Although chlorine deactivates the ring inductively, its lone pair donation stabilizes ortho/para Wheland intermediates. The sulfone is strongly electron withdrawing and meta directing; attack ortho or para to it produces especially unfavourable cationic contributors to resonance in chemistry. C2 is ortho to chlorine and meta to sulfone, whereas C3 has the opposite, less favourable relationship.

sulfuric acid protonates nitric acid, followed by loss of water to produce the nitronium ion. A ring pi bond attacks nitrogen, giving the Wheland intermediate with the new C–N bond. deprotonation at the attacked carbon restores aromaticity. This is electrophilic aromatic substitution: the aryl chloride and the sulfone both remain attached. The formula check is ${\mathrm{C}}_7{\mathrm{H}}_7\mathrm{Cl}{\mathrm{O}}_2\mathrm{S}+\mathrm{N}{\mathrm{O}}_2-\mathrm{H}={\mathrm{C}}_7{\mathrm{H}}_6\mathrm{ClN}{\mathrm{O}}_4\mathrm{S}$. It confirms replacement of one ring hydrogen rather than chlorine, but directing effects, rather than the formula alone, establish the position.

Oxazolination occurs para to oxygen on the ring that does not bear bromine. The product is 2-[4-(4-bromophenoxy)phenyl]-2-Oxazoline, shown in the final panel above. The brominated ring retains its para bromine; the other ring receives the new oxazolinyl group at its open para position.

The diaryl ether oxygen activates both rings toward electrophilic aromatic substitution. On the brominated ring, its least crowded para position is blocked, and bromine also decreases ring reactivity inductively. The unbrominated ring has an accessible para position, favored over its ortho sites by steric effects. This is substitution of an aromatic hydrogen, not displacement of the aryl bromide.

The formula provides a useful consistency check: ${\mathrm{C}}_{12}{\mathrm{H}}_9\mathrm{BrO}$ loses one aromatic H and acquires ${\mathrm{C}}_3{\mathrm{H}}_4\mathrm{NO}$, giving ${\mathrm{C}}_{15}{\mathrm{H}}_{12}\mathrm{BrN}{\mathrm{O}}_2$. It cannot by itself distinguish positional isomers; the directing and steric arguments select the connectivity.

The carbamate carbonyl oxygen attacks electrophilic sulfur of triflic anhydride, with cleavage of the anhydride S–O bond to release triflate. Donation of the nitrogen lone pair toward the carbonyl carbon then gives the indicated imidoyl-type cation: the former carbonyl oxygen now bears Tf, and the N–H nitrogen participates in a C=N${}^{+}$ bond. This converts a relatively unreactive carbamate carbonyl into a strongly electrophilic carbon bearing an excellent leaving group.

The aromatic pi bond para to ethoxy attacks that carbon. The C=N pi electrons move to nitrogen as the new aryl–carbon bond forms. Loss of the aromatic proton restores aromaticity; nitrogen donation and departure of the O-triflylated group restore the imine bond. proton transfers during the sequence and carbonate workup remove the remaining N–H proton. The surviving five-membered ring is an oxazoline: the product is 2-(4-ethoxyphenyl)-2-Oxazoline. An equivalent arrow order can eliminate the triflyloxy leaving group before arene capture; these are limiting descriptions of the activated electrophile, not a need to postulate an unactivated carbamate undergoing ordinary Friedel–Crafts acylation.

Ethoxy donates a lone pair into the ring, stabilizing the ortho and para Wheland intermediates. The para pathway avoids the crowding of an incoming heterocycle beside ethoxy, giving the observed position. Mechanistic experiments on this transformation include in situ carbon NMR of the activated reagent, competition experiments and isotope-effect measurements supporting electrophilic aromatic substitution; they do not directly image every intermediate.^[ref]