Efficient and Green Route to γ‐Lactams by Copper‐Catalysed Reversed Atom Transfer Radical Cyclisation of α‐Polychloro‐<i>N</i>‐allylamides, using a Low Load of Metal (0.5 mol%)

Bellesia, Franco; Clark, Andrew J.; Felluga, Fulvia; Gennaro, Armando; Isse, Abdirisak Ahmed; Roncaglia, Fabrizio; Ghelfi, Franco

doi:10.1002/adsc.201300132

Cited by 30 publications

(19 citation statements)

References 144 publications

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“…The IBN radicals acted as soluble halogen carriers to promote the HATRC reaction further . An attempt to lower the catalyst loading using ascorbic acid‐Na 2 CO 3 combination in ethanol by employing a method reported in literature– was ineffective due to the heterogeneous nature of the reaction mass (Table , entry ‐ 6 ). Reaction of enamine 20 a (Table , entry ‐ 5 ) with CuCl/PMDETA (0.7 eq) and AIBN (1 eq) in the presence of two equivalents of insoluble NaCl salt prolonged the reaction time from 6 h to 8 h, suggests towards low solubility of the reaction mass retarding the rate of reaction in entry 3 – 4 , 6 Table .…”

Section: Resultsmentioning

confidence: 99%

β,β,β‐Trichloroethyl‐NH‐Enamine as Viable System for 5‐Endo‐trig Radical Cyclization via Multifaceted Cu^I−Cu^II Redox Catalysis: Single Step Synthesis of Multi‐Functionalized NH‐Pyrroles

2019

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Here we report a mild and regioselective copper-catalyzed direct synthesis of multi-substituted and functionalized NH-pyrroles in high yields from diverse β,β,β-trichloroethyl-NH-enamines via a novel 5-endo-trig radical cyclization mode, previously known to be unviable in the enamine system. An approach to transform a geometrically 'disfavored to favored' 5-endo-trig radical cyclization mode in NH-enamine systems via multifaceted Cu I À Cu II redox catalysis generating radicals, preventing dehalogenative reduction of radical precursors and dehydrohalogenating the 5-endo-trig cyclized products have been demonstrated experimentally. With wider substrate scope, this method incorporates halo-, NH-and carbonyl functionalities besides alkyl, aryl and heteroaryl substituents in the pyrrole unit easily. These difficult to prepare 3-halo-NH-pyrroles are potential sources for natural products, agrochemicals, pharmaceuticals and organometallic chemistry. Scheme 1. a) Viable 5-endo-trig radical cyclizations in N-substituted enamide, b) unviable 5-endo-trig radical cyclizations in Nsubstituted enamine and c) transformation of unviable to viable mode in present work. UPDATES asc.wiley-vch.de Scheme 2. Synthesis of 3-chloro-NH-pyrroles 21 by Cu(I)/PMDETA-catalyzed 5-endo-trig radical cyclization-aromatization of NHenamines 20.Scheme 4. Study of the conformational role of substituents and functionalities of NH-enamines in the 5-endo-trig radical cyclization process.

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Section: Resultsmentioning

confidence: 99%

β,β,β‐Trichloroethyl‐NH‐Enamine as Viable System for 5‐Endo‐trig Radical Cyclization via Multifaceted Cu^I−Cu^II Redox Catalysis: Single Step Synthesis of Multi‐Functionalized NH‐Pyrroles

2019

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“…1 H NMR analysis of the crude product showed formation of a major single diastereomer (nearly 92%) along with small amounts of unidentifiable decomposition products due to the use of reflux conditions (Table , entry 3; Supporting Information, Figure S31). AIBN and ascorbic acid mediated ARGET‐ATRC, is highly successful in N ‐allyl‐α‐halo‐amides, a highly activated precursor with a pre‐protected nitrogen. However, in the cyclization of constitutionally different 2a , a less active haloalkyl precursor with free NH‐group, the amount of CuCl/PMDETA (1 mol%, to begin with) could be changed up to 10 mol%, only with AIBN (Table , entry 4; Supporting Information, Figure S32).…”

Section: Resultsmentioning

confidence: 99%

“…However, in the cyclization of constitutionally different 2a , a less active haloalkyl precursor with free NH‐group, the amount of CuCl/PMDETA (1 mol%, to begin with) could be changed up to 10 mol%, only with AIBN (Table , entry 4; Supporting Information, Figure S32). The cyclization of 2a did not occur completely (85%) using 10 mol% of CuCl 2 /PMDETA:ascorbic Acid/Na 2 CO 3 (1/1:5/10) in AcOEt/EtOH (3:1) at 35–40 °C even after 16 h, possibly due to lower solubility of copper complexes (isolated yield 68%; Supporting Information, Figure S33) among other factors. The presence of reactive NH‐groups in 2a , and 3a and acidity (also generated during the progress of the reaction) probably deactivated the Cu(I)/(II)‐species.…”

Section: Resultsmentioning

confidence: 99%

“…It possesses a high degree of functional group tolerance, and preserves all the halogen atoms in the cyclization products which is useful in performing halogen‐dependent transformations. Activators regenerated by the electron transfer (ARGET) process using reducing agents (AIBN, ascorbic acid, etc), and a platinum electrode surface (eATRC), represent a powerful technique in ATRC to reduce the catalyst loading drastically even below 1 mol%. Various nitrogenous ligands, in the complexation with Cu(I) halides, enhance the catalytic efficiency and regioselectivity in the cyclization step .…”

Section: Introductionmentioning

confidence: 99%

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Direct and Stereoselective Synthesis of Diversely Substituted 2,4‐trans‐(NH)‐Pyrrolidines by Copper(I)‐Catalyzed Radical Cyclization at Low Temperature

Ram

Gupta

2016

Adv Synth Catal

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This work describesasuccessfulc opper(I)catalyzed radical cyclization of b-haloethylallylamines bearing an unprotected NH-group while retaining catalyst-redox activity.T he cyclization occurs regio-and diastereoselectively at 0 8 8Ca nd furnishes diversely substituted 1,3-trans-(NH)-pyrrolidinesd irectly in high isolated yields.A ni nvolvement of the bulky copper complex in the cyclization step as the possible reason for the diastereoselectivity was proposed. Synthetica pplications of the productsi nt he preparation of useful 4-chloro-NH-pyrrole in as ingle step,h as also been demonstrated. Aq uick, mild and generalm ethod involving simple addition of trichloroacetic acid/dimethyl sulfoxide (CCl 3 CO 2 H-DMSO) solution to readily accessible N-allylaldimines and ketimines tolerating acid-sensitive and highly deactivating substituents was developed to access the amine precursors.

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“…These reagents appear by now to have a lower scope than tributyltin hydride, and this is valid also for our conditions, but in both cases, the work is still at an early stage. Current research aims at improving copper‐mediated ATR reactions, with lower catalyst loadings 27,32. As noted1 and also seen upon reducing reactive benzyl halides (Supporting Information, Table 6S), NaBH 3 CN may react through ionic pathways.…”

Section: Discussionmentioning

confidence: 99%

NaBH₃CN: A Janus Substitute for Tin‐Free Radical‐Based Reactions

2014

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Beside showing that thermal radical reactions (reduction, Giese reaction) are efficient if bromo‐/iodosugars are treated with NaBH3CN and 2,2″‐azobisisobutyronitrile, we explored new initiation conditions on the basis of CuI salts (≤0.5 equiv.) supposed to produce radicals from organobromides through a set. This was confirmed, as at about 50 °C under an inert atmosphere acetobromoglucose was reduced to the rearranged 2‐deoxyglucose and as N‐allyl α‐bromoamides reacted, depending on the conditions, either by reductive cyclization or atom‐transfer radical cyclization. A related cyclization occurred upon using Cu(OAc)2. This and other assays showed the reduction by NaBH3CN of CuII salts, either added or formed in situ. Having both ionic and radical reactivity, NaBH3CN appears as a Janus reagent that may be useful for tin‐free radical chemistry under mild and very simple conditions.

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Efficient and Green Route to γ‐Lactams by Copper‐Catalysed Reversed Atom Transfer Radical Cyclisation of α‐Polychloro‐N‐allylamides, using a Low Load of Metal (0.5 mol%)

Cited by 30 publications

References 144 publications

β,β,β‐Trichloroethyl‐NH‐Enamine as Viable System for 5‐Endo‐trig Radical Cyclization via Multifaceted Cu^I−Cu^II Redox Catalysis: Single Step Synthesis of Multi‐Functionalized NH‐Pyrroles

β,β,β‐Trichloroethyl‐NH‐Enamine as Viable System for 5‐Endo‐trig Radical Cyclization via Multifaceted Cu^I−Cu^II Redox Catalysis: Single Step Synthesis of Multi‐Functionalized NH‐Pyrroles

Direct and Stereoselective Synthesis of Diversely Substituted 2,4‐trans‐(NH)‐Pyrrolidines by Copper(I)‐Catalyzed Radical Cyclization at Low Temperature

NaBH₃CN: A Janus Substitute for Tin‐Free Radical‐Based Reactions

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Efficient and Green Route to γ‐Lactams by Copper‐Catalysed Reversed Atom Transfer Radical Cyclisation of α‐Polychloro‐N‐allylamides, using a Low Load of Metal (0.5 mol%)

Cited by 30 publications

References 144 publications

β,β,β‐Trichloroethyl‐NH‐Enamine as Viable System for 5‐Endo‐trig Radical Cyclization via Multifaceted CuI−CuII Redox Catalysis: Single Step Synthesis of Multi‐Functionalized NH‐Pyrroles

β,β,β‐Trichloroethyl‐NH‐Enamine as Viable System for 5‐Endo‐trig Radical Cyclization via Multifaceted CuI−CuII Redox Catalysis: Single Step Synthesis of Multi‐Functionalized NH‐Pyrroles

Direct and Stereoselective Synthesis of Diversely Substituted 2,4‐trans‐(NH)‐Pyrrolidines by Copper(I)‐Catalyzed Radical Cyclization at Low Temperature

NaBH3CN: A Janus Substitute for Tin‐Free Radical‐Based Reactions

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β,β,β‐Trichloroethyl‐NH‐Enamine as Viable System for 5‐Endo‐trig Radical Cyclization via Multifaceted Cu^I−Cu^II Redox Catalysis: Single Step Synthesis of Multi‐Functionalized NH‐Pyrroles

β,β,β‐Trichloroethyl‐NH‐Enamine as Viable System for 5‐Endo‐trig Radical Cyclization via Multifaceted Cu^I−Cu^II Redox Catalysis: Single Step Synthesis of Multi‐Functionalized NH‐Pyrroles

NaBH₃CN: A Janus Substitute for Tin‐Free Radical‐Based Reactions