Visible-light photoredox catalysis: direct synthesis of fused β-carbolines through an oxidation/[3 + 2] cycloaddition/oxidative aromatization reaction cascade in batch and flow microreactors

Abstract

Fused β-carbolines were synthesized via a visible light photoredox catalyzed oxidation/[3+2] cycloaddition/oxidative aromatization reaction cascade in batch and flow microreactors. Several structurally diverse heterocyclic scaffolds were obtained in good yields by coupling of tetrahydro-β-carbolines with a variety of dipolarophiles under photoredox multiple C-C bond forming events. The photoredox coupling of tetrahydro-β-carboline with 1,4-benzoquinone was significantly faster in continuous flow microreactor and the desired products were obtained in higher yields compared to batch reactor.

Visible‐Light/Photoredox‐Mediated sp3 CH Functionalization and Coupling of Secondary Amines with Vinyl Azides in Flow Microreactors

“…9 A flow microreactor for the synthesis of imidazole 9 a by visible‐light/[Ru(bpy) 3 ][PF 6 ] 2 ‐mediated coupling of vinyl azide 1 a and amine 2 a was easily assembled by wrapping a visible‐light‐transparent perfluoroalkoxy (PFA) capillary microreactor (ID=0.76 mm, Length=10 m, and volume=4.53 mL) over a white LED light source (Figure 2). 9c Solutions of vinyl azide 1 a and amine 2 a in acetonitrile, [Ru(bpy) 3 ][PF 6 ] 2 in acetonitrile, and TBHP in toluene were kept in three separate syringes and connections were made through an X‐junction. The effect of residence time over the coupling of vinyl azide 1 a and 1,2,3,4‐tetrahydroisoquinoline ( 2 a ) was studied in the flow microreactor.…”

Post‐Pictet‐Spengler Cyclization (PPSC): A Strategy to Synthesize Polycyclic β‐Carboline‐Derived Natural Products and Biologically Active N‐Heterocycles

“…reported a visible light‐driven photocascade catalysis strategy which demonstrated the use of both energy transfer and electron transfer pathways collectively, for the library synthesis of pentacyclic tetrahydro‐β‐carboline framework having a strained aziridine ring system . Initially, the Pictet‐Spengler reaction between tryptamine and formaldehyde resulted in the formation of THβC adduct 39 which on nucleophilic substitution reaction with α‐bromoketone generated N ‐alkyl THβC 40 (Scheme ). Compound 40 was then coupled with vinyl azide analogues 41 using Ru(bpy) 3 (PF 6 ) 2 , TBHP (oxidant), and CH 3 CN in the presence of 17 W white LED at room temperature to generate a library of compounds ( 43 , 60–70% yield) with high regio‐ and diastereoselectivity.…”

Designing Microflowreactors for Photocatalysis Using Sonochemistry: A Systematic Review Article

“…Because of its advantages, the synthesis of nanoparticles in microfluidics has become prominent in the past years [5]. The use of continuous microreactor led to the improvement of irradiation over the reaction mixture and offers a considerably reduced reaction time and better yields of products compared to batch reactors [25]. Batch reactors have a major disadvantage in the linear decrease in the intensity of the electromagnetic radiation with the square of the distance of the light source used [26,27].…”