Continuous Flow Photochemical and Thermal Multi-Step Synthesis of Bioactive 3-Arylmethylene-2,3-Dihydro-1H-Isoindolin-1-Ones

Abstract

An effective multi-step continuous flow approach towards N-diaminoalkylated 3-arylmethylene-2,3-dihydro-1H-isoindolin-1-ones, including the local anesthetic compound AL-12, has been realized. Compared to the traditional decoupled batch processes, the combined photochemical-thermal-thermal flow setup rapidly provides the desired target compounds in superior yields and significantly shorter reaction times.Abstract: An effective multi-step continuous flow approach towards N-diaminoalkylated 3arylmethylene-2,3-dihydro-1H-isoindolin-1-ones, including the local anesthetic compound AL-12, has been realized. Compared to the traditional decoupled batch processes, the combined photochemical-thermal-thermal flow setup rapidly provides the desired target compounds in superior yields and significantly shorter reaction times.

Continuous Flow Photochemistry for the Preparation of Bioactive Molecules

“…The synthesis of 3-hydroxyazetidines via a continuous Norrish-Young photocyclization reaction ( Figure 11B) represents a further demonstration of effectively creating drug-like structures in a simple and atom-economical fashion, and a recent study reports on the versatility of this transformation [64]. A final example outlines the combination of photochemical with thermal processes in a reaction sequence rendering several isoindolin-1-one derivatives in a continuous manner, in which a photobenzylation of substituted phthalimides features as key step [65] ( Figure 11C).…”

Technological Innovations in Photochemistry for Organic Synthesis: Flow Chemistry, High-Throughput Experimentation, Scale-up, and Photoelectrochemistry

“…A number of photochemical decarboxylation reactions involving phthalimides were described using different reactor systems. ,,− These decarboxylations were performed in a conventional chamber photoreactor, in an advanced falling-film reactor and in continuous-flow reactors. A performance comparison was carried out by Oelgemöller et al between a commercially available batch and flow reactor (Scheme A) .…”

Multi‐Step Continuous‐Flow Organic Synthesis: Opportunities and Challenges

“…In 2019, Oelgemöller and co‐workers successfully developed a streamlined synthetic strategy for 3‐arylmethylene‐2,3‐dihydro‐1 H ‐isoindolin‐1‐ones, compounds with different biological activities, including anesthesia [34] . The continuous‐flow approach combined a photochemical and thermal setup.…”

“…In 2019, Oelgemçllera nd co-workerss uccessfully developed as treamlined synthetic strategy for 3-arylmethylene-2,3-dihydro-1 H-isoindolin-1-ones, compounds with differentb iological activities, including anesthesia. [34] The continuous-flow approach combined ap hotochemical and thermals etup. The telescoped flow operation provided rapid ande fficient access to the target compounds (73 substrates, average product yield of 75 %; Figure32).…”