Visible Light Photocatalytic Synthesis of Tetrahydroquinolines Under Batch and Flow Conditions

Abstract

In this work, we describe the use of visible light and a photocatalytic system for the cyclization of iodoaryl vinyl derivatives to tetrahydroquinoline structures. The reaction proceeds under very mild conditions, tolerates different functional groups and more importantly, the method allows the synthesis The synthesis of tetrahydroquinolines (THQs) is of special interest, since they are heterocyclic structures present in natural and unnatural compounds with interesting biological properties (Scheme 1a). [1] For example, tetrahydroquinolines display anti-HIV activity (I), [2] antifungal properties against Cladosporium cladosporioides, yeasts, hialohyphomycetes and dermatophytes (II), [3] and antitumor (III) [4] as well as antidepressant activities (IV). [5] Therefore, new approaches and strategies for the synthesis of this class of molecules are one of the main objectives of the modern synthetic chemistry. [1a] In this regard, among all the synthetic methods available for preparing THQs, radical chemistry has proven to be a straightforward methodology with a good functional group tolerance. In fact, different synthesis of THQs have been reported under radical conditions, most of them using tin sources as hydrogen donor and AIBN as initiator (Scheme 1b). [6] In these methodologies, given the energetic reaction conditions (usually 80-100°C) required, the control in the regioselectivity of the reaction (6 exo-trig vs 7 endo-trig cyclization) is not very predictable, normally giving a mixture of products. Moreover, the protection (PG) of the start-[a

Enhancing Visible-Light Photocatalysis via Endohedral Functionalization of Single-Walled Carbon Nanotubes with Organic Dyes

“…Interestingly, 5 was able to convert electron-poor substrates such as iodobenzonitrile ( 7a ), which was fully dehalogenated in 16 h. Finally, the catalytic performance of PTH@oSWNT was expanded further by studying different C–C bond formation photoreactions, which are important reactions from a synthetic point of view. Thus, the encapsulated hybrid material was also able to accomplish the light-mediated synthesis of tetrahydroisoquinoline ( 7q ) with a 52% yield, starting from the corresponding iodide 6q in a 6- exo cycling procedure . On the other hand, 5 was able to afford the α-alkylation of aliphatic aldehydes ( 8a ) with diethyl-bromomalonate 6r with a very good conversion (99%) and enantioselectivity (97% ee). , To check for any modifications after reaction, the material was also analyzed by Raman spectroscopy, TGA, and elemental analysis, but no alterations were detected (see Figures S7 and S8 in the Supporting Information).…”

“…Thus, the encapsulated hybrid material was also able to accomplish the light-mediated synthesis of tetrahydroisoquinoline (7q) with a 52% yield, starting from the corresponding iodide 6q in a 6-exo cycling procedure. 38 On the other hand, 5 was able to afford the α-alkylation of aliphatic aldehydes (8a) with diethylbromomalonate 6r with a very good conversion (99%) and enantioselectivity (97% ee). 39,40 To check for any modifications after reaction, the material was also analyzed by Raman spectroscopy, TGA, and elemental analysis, but no alterations were detected (see Figures S7 and S8 in the Supporting Information).…”

Visible Light‐Mediated Cyclisation Reaction for the Synthesis of Highly‐Substituted Tetrahydroquinolines and Quinolines

“…Yang and co‐workers recently demonstrated the one‐pot photo‐initiated enantioselective synthesis of 2‐substituted THQs, [10g] via the cyclisation of 2‐aminoenones to the corresponding quinoline, ( E )/( Z ) isomerisation, and subsequent chiral phosphoric acid‐catalysed enantioselective hydrogenation to the THQ. Aleman and co‐workers reported the photocatalytic reduction of iodoaryl vinyl derivatives to the corresponding aryl radical, [11d] which undergoes a 6 ‐exo‐trig cyclisation to afford the THQ both in batch and in flow. Though these reports document significant advantages, including avoiding the use of stoichiometric radical initiators and high temperatures, they reveal a limited substrate scope, especially to access substitution at each of the 2‐, 3‐, and 4‐positions of THQ, whilst only a single example contained a pyridyl functionality [12] .…”

Solvent-Free Visible Light Photocatalytic Oxidation Processes Mediated by Transparent Films of an Imine-Based Organic Polymer

“…However, the scarcity, high cost and toxicity of these metals has pushed forward the research on organic photocatalysts. Among them, phenyl phenothiazine (PTH) derivatives have been successfully used in dye-sensitized solar cells (DSSCs) [9][10][11], water splitting [12], hydrogen production [13][14][15][16][17], pollutant degradation [18] and organic synthesis [19][20][21][22].…”