Build, Then Functionalise in the Same Pot: Organic-Dye Photocatalytic Construction of Quinoline, Quinoxaline and Imidazopyridine Cores Telescoped with C3 Chalcogenation, Alkylation and Amination

Abstract

Photocatalytic ring construction and photocatalytic C–H functionalisation are usually developed separately, even though the same dyes, solvents and light sources serve both. We asked whether a heterocycle can be built aerobically and then functionalised in the same vessel, and what such telescoping costs or saves. Three dye-catalysed annulations were first established on a common 0.20 mmol basis. 2-Aminopyridine and acetophenone gave the imidazo[1,2-a]pyridine IP01 (MB/KI, 660 nm; 85% isolated). Aniline, ethyl glyoxylate and styrene gave the quinoline-2-carboxylate QN01 (eosin Y with 10 mol% acid, 525 nm; 74%), and o-phenylenediamine and phenacyl alcohol gave 2-phenylquinoxaline QX01 (eosin Y, 525 nm; 86%). Before any reaction mixtures were combined, a robustness screen measured how much each likely carryover component (ethanol, water, iodide, acid, residual amine, oxygen) suppressed each second stage. Acid (21–45% yield retention) and the wrong atmosphere (48–65%) were the most damaging. On that basis three staged sequences were developed: C3 phenylthiolation of IP01 (T1, 72% overall), Minisci-type C3 cyclohexylation of QX01 after an air-to-argon switch (T2, 65%), and C3 amination of N-methylquinoxalin-2(1H)-one with morpholine (T3, 70%). Adding the second reagent at the start lowered yields to 38% (T1) and 29% (T3). Against matched stepwise routes, telescoping cost 2.8–5.5 percentage points of overall yield but reduced process mass intensity by 38–42% (148 → 86, 182 → 112, 136 → 79).