Efficient Use of Photons in Photoredox/Enamine Dual Catalysis with a Peptide-Bridged Flavin–Amine Hybrid

Tagami, Takuma; Arakawa, Yukihiro; Minagawa, Keiji; Imada, Yasushi

doi:10.1021/acs.orglett.9b02567

Cited by 15 publications

(8 citation statements)

References 37 publications

(20 reference statements)

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“…To probe the latter possibility, the reaction quantum yield (Φ prod ) was measured for the reaction of cyclohexylamine 1a with styrene 6b and found to be 0.31 (at 66% conversion to 7ab by NMR) . Given that quantum efficiencies for dual catalytic photoredox processes in which a cocatalyst is the quencher are typically very low (Φ prod < 0.1), , a value of 0.31 is suggestive of at least some contribution from an innate chain (with a photonically inefficient initiation step). The operation of a photoredox process in parallel with an innate chain thus cannot be excluded .…”

Section: Resultsmentioning

confidence: 99%

Photocatalytic Hydroaminoalkylation of Styrenes with Unprotected Primary Alkylamines

et al. 2021

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Catalytic, intermolecular hydroaminoalkylation (HAA) of styrenes provides a powerful disconnection for pharmacologically relevant γ-arylamines, but current methods cannot utilize unprotected primary alkylamines as feedstocks. Metal-catalyzed HAA protocols are also highly sensitive to α-substitution on the amine partner, and no catalytic solutions exist for α-tertiary γ-arylamine synthesis via this approach. We report a solution to these problems using organophotoredox catalysis, enabling a direct, modular, and sustainable preparation of α-(di)substituted γ-arylamines, including challenging electron-neutral and moderately electron-rich aryl groups. A broad range of functionalities are tolerated, and the reactions can be run on multigram scale in continuous flow. The method is applied to a concise, protecting-group-free synthesis of the blockbuster drug Fingolimod, as well as a phosphonate mimic of its in vivo active form (by iterative α-C–H functionalization of ethanolamine). The reaction can also be sequenced with an intramolecular N -arylation to provide a general and modular access to valuable (spirocyclic) 1,2,3,4-tetrahydroquinolines and 1,2,3,4-tetrahydronaphthyridines. Mechanistic and kinetic studies support an irreversible hydrogen atom transfer activation of the alkylamine by the azidyl radical and some contribution from a radical chain. The reaction is photon-limited and exhibits a zero-order dependence on amine, azide, and photocatalyst, with a first-order dependence on styrene.

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Section: Resultsmentioning

confidence: 99%

Photocatalytic Hydroaminoalkylation of Styrenes with Unprotected Primary Alkylamines

et al. 2021

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“…However, because of the distal chiral stereocenter from the active site, the reaction was not enantioselective. 70 Nevertheless, the flavin antenna was demonstrated to be efficient to induce a remote SET mechanism.…”

Section: Alkylation Of Aldehydesmentioning

confidence: 99%

Enantioselective Radical Reactions Using Chiral Catalysts

Mondal¹,

et al. 2022

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Scheme 24 Enantioselective Radical Hydroacylation of Enals with α-Ketoacids byMerging Photoredox Catalysis with Amine Catalysis.Jang et al. exploited enantioselective tandem Michael addition/oxyamination of α,β-unsaturated aldehydes by combining asymmetric iminium catalysis using organocatalyst with photoinduced SOMO catalysis using N719/TiO2. 60 Here, TiO2 acts as a second cooperative photocatalyst along with Ru photocatalyst N719 which bound to the latter, increases the enantio-and diastereoselectivity of the process. Adamantane carboxylic acid (30 mol%) was used as an additive which promotes formation of iminium ion 2.1.48A from aldehyde 2.1.48 and chiral amine catalyst. This iminium intermediate then reacts with diethyl malonate to provide intermediate 2.1.48B which either undergoes hydrolysis to form β-substituted aldehyde 2.1.50 or photo-oxidation by the photoexcited Ru(II) dye to form enamine radical 2.1.48C. Subsequent addition of TEMPO to radical intermediate 2.1.48BC followed by hydrolysis afforded the desired product 2.1.49 (Scheme 25). This mechanism is obeying to a polar/radical crossover sequence where the first stereocontrol arises from the addition of the malonate.Recently, Bach group reported promising preliminary results of enantioselective [2+2] photocycloaddition of cinnamaldehyde in the presence of ruthenium photocatalyst and proline derived organocatalyst. 61

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“…Imada, Arakawa, and co-workers achieved dual enamine catalysis with designed flavin 39, which contains a secondary amine unit connected to the isoalloxazine core with a proline linker. 82 Catalyst 39 was applied in the -functionalization of aliphatic aldehydes with TEMPO (Scheme 24). The efficiency of the designed flavin compared to unmodified analogues or (-)-riboflavin was rationalized by a significant increase in reaction quantum yield of up to Φ = 0.80 with flavin 39.…”

Section: Scheme 23mentioning

confidence: 99%

Molecular Editing of Flavins for Catalysis

Rehpenn¹,

Walter²,

Storch³

2021

Synthesis

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The diverse activity of flavoenzymes in organic transformations has fascinated researchers for a long time. However, when applied outside an enzyme environment, the isolated flavin cofactor only shows largely reduced activity. This highlights the importance of embedding the reactive flavin’s isoalloxazine core in defined surroundings. The latter include crucial non-covalent interactions with amino acid side chains or backbone as well as controlled access to reactants such as molecular oxygen. Nevertheless, molecular flavins are increasingly applied in the organic laboratory as valuable organocatalysts. Chemical modification of the parent isoalloxazine structure is of particular interest in this context in order to achieve reactivity and selectivity in transformations, which are so far only known with flavoenzymes or even unprecedented. This review aims to give a systematic overview of the reported designed flavin catalysts and highlights the impact of each structural alteration. It is intended to serve as a source of information when comparing the performance of known catalysts, but also when designing new flavins. Over the last decades, molecular flavin catalysis has emerged from proof-of-concept reactions to increasingly sophisticated transformations. This stimulates anticipating new flavin catalyst designs for solving contemporary challenges in organic synthesis.

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Efficient Use of Photons in Photoredox/Enamine Dual Catalysis with a Peptide-Bridged Flavin–Amine Hybrid

Cited by 15 publications

References 37 publications

Photocatalytic Hydroaminoalkylation of Styrenes with Unprotected Primary Alkylamines

Photocatalytic Hydroaminoalkylation of Styrenes with Unprotected Primary Alkylamines

Enantioselective Radical Reactions Using Chiral Catalysts

Molecular Editing of Flavins for Catalysis

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