Radical alkylation of <i>para</i>-quinone methides with 4-substituted Hantzsch esters/nitriles <i>via</i> organic photoredox catalysis

Wu, Qing-Yan; Min, Qing-Qiang; Ao, Gui-Zhen; Liu, Feng

doi:10.1039/c8ob01641k

Cited by 42 publications

(12 citation statements)

References 42 publications

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“…All reactions were carried out under a dry nitrogen atmosphere by using standard Schlenk techniques. 1a , 1a-Br , 1b , 1c , 1i , 2a , 2b , 2c , 2d , 2e , 2g , 2h , 2i , 2j , 2k , 2l , 2m , 2n , 2o , 2p , 2r , 2s , 4a , 4c , and 5aa were prepared according to the literature procedures. Other reagents including starting materials for the preparation of 1a – j , 2a – s , 4a – c , 1a-Cl , fac -[Ir(ppy) 3 ], fac -[Ir(Fppy) 3 ], anhydrous NiCl 2 , ligands (bpy, dtbbpy, dMebpy, dMeObpy), bases, TEMPO, and solvents were obtained from commercial sources.…”

Section: Experimental Sectionmentioning

confidence: 99%

“…The use of visible light excitement of a photoredox catalyst, followed by single-electron-transfer (SET) processes, leads to the generation of alkyl radicals from 4-alkyl-1,4-dihydropyridines, 1,2,14 enabling not only simple alkylation 3−5 but also alkylative reactions accompanied by other transformations such as cross-coupling reactions in the presence of additional catalysts. [6][7][8][9][10][11][12][13]15 In fact, we have recently succeeded in photoredox-catalyzed aromatic substitution reactions of cyanoarenes with 4-alkyl-1,4-dihydropyridines 3 and cooperative nickel-and photoredox-catalyzed crosscoupling reactions of aryl and alkenyl halides with 4-alkyl-1,4-dihydropyridines. 8,9 In the course of our study to expand the utility of 4-alkyl-1,4dihydropyridines toward alkylative reactions, we next planned to apply 4-alkyl-1,4-dihyropyridines to the alkylative cyclization reactions of haloalkynes.…”

Section: ■ Introductionmentioning

confidence: 99%

“…Recently, our group and others have demonstrated that 4-alkyl-1,4-dihydropyridines can be used as powerful alkylation reagents to offer a variety of alkylative reactions in photoredox-catalyzed molecular transformations, − providing an alternative to using classical, but highly reactive, organometallic alkylation reagents. The use of visible light excitement of a photoredox catalyst, followed by single-electron-transfer (SET) processes, leads to the generation of alkyl radicals from 4-alkyl-1,4-dihydropyridines, ,, enabling not only simple alkylation − but also alkylative reactions accompanied by other transformations such as cross-coupling reactions in the presence of additional catalysts. − , In fact, we have recently succeeded in photoredox-catalyzed aromatic substitution reactions of cyanoarenes with 4-alkyl-1,4-dihydropyridines and cooperative nickel- and photoredox-catalyzed cross-coupling reactions of aryl and alkenyl halides with 4-alkyl-1,4-dihydropyridines. , …”

Section: Introductionmentioning

confidence: 99%

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Cooperative Photoredox- and Nickel-Catalyzed Alkylative Cyclization Reactions of Alkynes with 4-Alkyl-1,4-dihydropyridines

et al. 2021

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Cooperative photoredox- and nickel-catalyzed alkylative cyclization reactions of iodoalkynes with 4-alkyl-1,4-dihydropyridines as alkylation reagents under visible light irradiation have been achieved to afford the corresponding alkylated cyclopentylidenes in good to high yields. Introduction of substituents at the propargylic position of iodoalkynes has led to the stereoselective formation of E-isomers. The present reaction system provides a novel synthetic method for alkylative cyclization reactions of both terminal and internal alkynes with cooperative photoredox and nickel catalysis.

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Section: Experimental Sectionmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Cooperative Photoredox- and Nickel-Catalyzed Alkylative Cyclization Reactions of Alkynes with 4-Alkyl-1,4-dihydropyridines

et al. 2021

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“…With the development of visible‐light‐promoted photoredox catalysis, p ‐QMs have emerged as radical precursors for generating diarylmethyl radical intermediates through a photocatalytic single electron reduction process [13] . A variety of structurally diverse diarylmethane derivatives could be easily obtained via photoredox‐catalyzed di‐/trifluoromethylation, [13c,f,i] alkylation, [13d] decarboxylative addition, [13h] and cyanoalkylation [13g] of p ‐QMs. In particular, Lu et al [14] .…”

Section: Figurementioning

confidence: 99%

An Efficient Approach to Access 2,2‐Diarylanilines via Visible‐Light‐Promoted Decarboxylative Cross‐Coupling Reactions

et al. 2021

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A straightforward protocol for the visible‐light‐promoted decarboxylative 1,6‐conjugate addition of N‐aryl glycines to para‐quinone methides under transition‐metal‐free conditions is disclosed. This method provides scalable and efficient access to 2,2‐diarylanilines with biological and pharmacologic potential in good to excellent yields (39 examples, up to 97% yield). The synthetic utility of this work has been illustrated in the efficient synthesis of 3‐substituted indoline.

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“…(20) The propensity for over-reduction is unclear, but a potential intramolecular [1,4]-HAT event from the α-amino radical instead of Giese addition could be responsible. (21) Tahara, A.; Miyamoto, Y.; Aoto, R.; Shigeta, K.; Une, Y.; Sunada, Y.; Motoyama, Y.; Nagashima, H. Catalyst Design of Vaska-Type Iridium Complexes for Highly Efficient Synthesis of π-Conjugated Enamines. Organometallics 2015, 34, 4895-4907.…”

Section: Scheme 8 (A) Identification Of Possible Yield-determining Pmentioning

confidence: 99%

Reverse Polarity Reductive Functionalization of Tertiary Amides via a Dual Iridium-Catalyzed Hydrosilylation and Single Electron Transfer Strategy

et al. 2020

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A new strategy for the mild generation of synthetically valuable α-amino radicals from robust tertiary amide building blocks has been developed. By combining Vaska's complex-catalyzed tertiary amide reductive activation and photochemical single electron reduction into a streamlined tandem process, metastable hemiaminal intermediates were successfully transformed into nucleophilic α-amino free radical species. This umpolung approach to such reactive intermediates was exemplified through coupling with an electrophilic dehydroalanine acceptor, resulting in the synthesis of an array of α-functionalized tertiary amine derivatives, previously inaccessible from the amide starting materials. The utility of the strategy was expanded to include secondary amide substrates, intramolecular variants and late stage functionalization of an active pharmaceutical ingredient. DFT analyses were used to establish the reaction mechanism and elements of the chemical system that were responsible for the reaction's efficiency. Scheme 1. α-Functionalization strategies for amine synthesis from tertiary amides Scheme 3. Optimization studies for (A) Vaska's catalyzed amide hydrosilylation. (B) The photocatalytic reductive coupling of the silyl hemiaminal intermediate with DHA derivative. stituted structures delivered tertiary amine products, although a steric increase vs. reaction efficiency trend was observed. 19 Intramolecular Cyclization. We recognized the opportunity that this tandem amide activation protocolthrough tethering an alkene acceptor to the alkyl chain of the amide starting material-could be suitably leveraged towards the synthesis of complex heterocyclic amine frameworks. Accordingly, model substrates bearing a pendant α,β-unsaturated ester (1s-1t) were prepared, but initial studies demonstrated that these motifs did not readily undergo hydrosilylation using Vaska's catalyst (only around 80% conversion was achieved after 8 hours of reaction time), and furthermore significant quantities of over reduction side-product were isolated following the photocatalytic step. 20 Nevertheless, these initial challenges were circumvented when a derivative of Vaska's complex bearing triphenylphosphite ligands-previously reported by Nagashima 21-was employed in the hydrosilylation step instead (Scheme 5). Pleasingly, clean conversion to a stable silyl hemiaminal species was achieved within one hour, and subsequent subjection to the optimized photoredox conditions delivered the desired cyclic pyrrolidine (4s) and piperidine (4t) products in good yields. Scheme 5. Extension of the Vaska-photoredox system for reductive cyclization of tertiary amides Secondary Amide Activation. Recent endeavors by Chida and Sato, and Huang have demonstrated the utility of [Ir(COE)2Cl]2 complex in conjunction with Et2SiH2 reductant for the nucleophilic reductive functionalization of secondary amide building blocks, affording the corresponding α-branched secondary amine products. 4e,f Scheme 6. Reverse polarity, photocatalytic reductive functionalization of seconda...

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Radical alkylation of para-quinone methides with 4-substituted Hantzsch esters/nitriles via organic photoredox catalysis

Cited by 42 publications

References 42 publications

Cooperative Photoredox- and Nickel-Catalyzed Alkylative Cyclization Reactions of Alkynes with 4-Alkyl-1,4-dihydropyridines

Cooperative Photoredox- and Nickel-Catalyzed Alkylative Cyclization Reactions of Alkynes with 4-Alkyl-1,4-dihydropyridines

An Efficient Approach to Access 2,2‐Diarylanilines via Visible‐Light‐Promoted Decarboxylative Cross‐Coupling Reactions

Reverse Polarity Reductive Functionalization of Tertiary Amides via a Dual Iridium-Catalyzed Hydrosilylation and Single Electron Transfer Strategy

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