Exploiting Photochemical Processes in Multi‐Step Continuous Flow: Derivatization of the Natural Product Clausine C

Abstract

The synthesis and derivatization of carbazoles based upon the natural product clausine C has been accomplished using two different two‐step continuous processes. The resulting carbazoles (9 examples, 33–74 % yield) were prepared by means of a continuous flow set‐up integrating a UV‐mediated transformation employing a purple LED reactor (λ=394 nm) as the first step in the multi‐step sequence. The second derivatization step involved cross‐coupling through Pd‐catalyzed Suzuki cross‐coupling or Ni‐catalyzed metallophotoredox cross‐coupling with potassium trifluoroborate salts. The latter represents the first example of using sequential photochemical reactors, at different wavelengths, in a continuous flow process.

Photocatalyic Appel reaction enabled by copper-based complexes in continuous flow

“…Following the optimization of the catalyst structure and exploration of scope, the batch reaction conditions were then transferred to continuous flow ( Table 2 ). Initially, an experimental set-up using a previously reported reactor for purple LEDs was selected for the reaction [ 30 – 31 ]. Following injection of the reaction mixture with a target residence time of 60 min, only traces of the desired bromide 2 were observed.…”

Continuous Flow Photochemistry for the Preparation of Bioactive Molecules

“…More recent examples describe routes towards various poly(ADP-ribose) polymerase inhibitors aided by an intramolecular photocyclization reaction [58], unnatural aza-rocaglates via an excited state intramolecular proton transfer (ESIPT)-mediated (3 + 2) photocycloaddition [59] or the preparation of new derivatives of clausine A via an azide-mediated carbazole formation followed by an arylation reaction [60] (Figure 9). Pyocyanin, a small naturally occurring virulence factor, was recently prepared in an effective and scalable multi-step approach featuring a photochemical oxygenation reaction ( Figure 10).…”

Two Colour Photoflow Chemistry for Macromolecular Design

“…[8] Such a strategy allows to induce reactivity of a reactant mixture at a certain interval of the reactor with one light source, followed by the initiation of another reaction, independent of the former process, with a second source. [9] Subsequent reactions can be triggered with other wavelengths, without interfering with the former irradiation paths. Therefore, the flow setup can facilitate multi-step processes comparable to a "one-pot" synthesis strategy by allowing controlled and efficient irradiation of the reactant mixture at all time.…”