Photoredox Alkenylation of Carboxylic Acids and Peptides: Synthesis of Covalent Enzyme Inhibitors

Kammer, Lisa Marie; Lipp, Benjamin; Opatz, Till

doi:10.1021/acs.joc.8b02759

Cited by 27 publications

(16 citation statements)

References 69 publications

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“…Successful formation of ester 64 required the addition of biphenyl (10 mol%) as a redox mediator to decrease BET, which has been reported as an issue with DCA. 64 (See later for further discussion. )…”

Section: Bicatalytic Processesmentioning

confidence: 99%

Recent advances in visible light-activated radical coupling reactions triggered by (i) ruthenium, (ii) iridium and (iii) organic photoredox agents

2021

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Section: Bicatalytic Processesmentioning

confidence: 99%

Recent advances in visible light-activated radical coupling reactions triggered by (i) ruthenium, (ii) iridium and (iii) organic photoredox agents

2021

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“…The chloromethyl radical generation by photoredox catalysis is a useful strategy for cyclopropanation [58]. Most photoredox catalyzed, decarboxylative generations of carbon-centered radicals are based on the formation of "stabilized" α-amino [59][60][61][62][63][64][65] or benzyl [66][67][68][69][70] radical species. However, the generation of unstabilized alkyl radical species is also known [71][72][73][74].…”

Section: Resultsmentioning

confidence: 99%

Visible-light-induced addition of carboxymethanide to styrene from monochloroacetic acid

Vliet¹,

Leeuwen²,

Brouwer³

et al. 2020

Beilstein J. Org. Chem.

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Where monochloroacetic acid is widely used as a starting material for the synthesis of relevant groups of compounds, many of these synthetic procedures are based on nucleophilic substitution of the carbon chlorine bond. Oxidative or reductive activation of monochloroacetic acid results in radical intermediates, leading to reactivity different from the traditional reactivity of this compound. Here, we investigated the possibility of applying monochloroacetic acid as a substrate for photoredox catalysis with styrene to directly produce γ-phenyl-γ-butyrolactone. Instead of using nucleophilic substitution, we cleaved the carbon chlorine bond by single-electron reduction, creating a radical species. We observed that the reaction works best in nonpolar solvents. The reaction does not go to full conversion, but selectively forms γ-phenyl-γ-butyrolactone and 4-chloro-4-phenylbutanoic acid. Over time the catalyst precipitates from solution (perhaps in a decomposed form in case of fac-[Ir(ppy)3]), which was proven by mass spectrometry and EPR spectroscopy for one of the catalysts (N,N-5,10-di(2-naphthalene)-5,10-dihydrophenazine) used in this work. The generation of HCl resulting from lactone formation could be an additional problem for organometallic photoredox catalysts used in this reaction. In an attempt to trap one of the radical intermediates with TEMPO, we observed a compound indicating the generation of a chloromethyl radical.

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“…Very recently, Opatz presented a method for the decarboxylation of the COOH moiety of peptides, converting it into an αamino radical before radical addition to Michael acceptors (e.g., vinyl sulfone and acrylonitrile) with 9,10-dicyanoanthracene (DCA) as an organic photoredox catalyst (Scheme 44). 169 The examples listed in Scheme 44B exhibited how this tactic could be used to conveniently synthesize complex biomolecules as lead structures for potential biological evaluation. Accordingly, functionalization of compound 44-5, which is derived from Fmoc-L-phenylalanine 44-4 followed by late-stage manipulation, provided the potent cysteine protease inhibitor K11777 in three straightforward steps with 27% overall yield.…”

Section: Radical-mediated Desulfonylation Of Vinylic Sulfonesmentioning

confidence: 99%

Desulfonylation via Radical Process: Recent Developments in Organic Synthesis

et al. 2021

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As the "chemical chameleon", sulfonyl-containing compounds and their variants have been merged with various types of reactions for the efficient construction of diverse molecular architectures by taking advantage of their incredible reactive flexibility. Currently, their involvement in radical transformations, in which the sulfonyl group typically acts as a leaving group via selective C−S, N−S, O−S, S−S, and Se−S bond cleavage/ functionalization, has facilitated new bond formation strategies which are complementary to classical two-electron cross-couplings via organometallic or ionic intermediates. Considering the great influence and synthetic potential of these novel avenues, we summarize recent advances in this rapidly expanding area by discussing the reaction designs, substrate scopes, mechanistic studies, and their limitations, outlining the state-of-the-art processes involved in radical-mediated desulfonylation and related transformations. With a specific emphasis on their synthetic applications, we believe this review will be useful for medicinal and synthetic organic chemists who are interested in radical chemistry and radical-mediated desulfonylation in particular. CONTENTS

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Photoredox Alkenylation of Carboxylic Acids and Peptides: Synthesis of Covalent Enzyme Inhibitors

Cited by 27 publications

References 69 publications

Recent advances in visible light-activated radical coupling reactions triggered by (i) ruthenium, (ii) iridium and (iii) organic photoredox agents

Recent advances in visible light-activated radical coupling reactions triggered by (i) ruthenium, (ii) iridium and (iii) organic photoredox agents

Visible-light-induced addition of carboxymethanide to styrene from monochloroacetic acid

Desulfonylation via Radical Process: Recent Developments in Organic Synthesis

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