Dearomative Photocatalytic Construction of Bridged 1,3‐Diazepanes

Leitch, Jamie A.; Rogova, Tatiana; Duarte, Fernanda; Dixon, Darren J.

doi:10.1002/anie.201914390

Cited by 75 publications

(41 citation statements)

References 138 publications

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“…For instance, an excellent way towards construction of tricyclic products via a reductive diversion of the Minisci reaction was recently reported by Duarte and Dixon. 121 Interestingly, if the emitter can generate two or more TADF-active states (Fig. 22(a)), or if the conditions for both TADF and TTA are satisfied (Fig.…”

Section: Dual Delayed Fluorescencementioning

confidence: 99%

Dual emission in purely organic materials for optoelectronic applications

2021

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Section: Dual Delayed Fluorescencementioning

confidence: 99%

Dual emission in purely organic materials for optoelectronic applications

2021

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“…Thedegree of p-orbital overlap that could be achieved in the transition states of the 3am exo and endo structures possibly has agreater effect on the energy difference than for the diastereomers of 3aa.This change in atomic arrangement of radical addition accounts for the switch in diastereoselectivity. [31,32]…”

Section: Methodsmentioning

confidence: 99%

Dearomative Photocatalytic Construction of Bridged 1,3-Diazepanes

Leitch

Rogova

Duarte

et al. 2019

Preprint

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The construction of diverse sp 3 -rich skeletal ring systems is of importance to drug discovery programmes and natural product synthesis.Herein, we report the photocatalytic construction of 2,7-diazabicyclo[3.2.1]octanes (bridged 1,3diazepanes) via ar eductive diversion of the Minisci reaction. The fused tricyclic product is proposed to form via radical addition to the C4 position of 4-substituted quinoline substrates,with subsequent Hantzschester-promoted reduction to ad ihydropyridine intermediate whichu ndergoes in situ twoelectron ring closure to form the bridged diazepane architecture.Awide scope of N-arylimine and quinoline derivatives was demonstrated and good efficiency was observed in the construction of sterically congested all-carbon quaternary centers.C omputational and experimental mechanistic studies provided insights into the reaction mechanism and observed regioselectivity/diastereoselectivity. Scheme 1. Photoredox catalysis in reverse polarity synthesis, and proposed concept for quinoline functionalization.

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“…. (15) For reviews see: ( 18Anhydrous conditions were essential to prevent iminium ion hydrolysis. Toluene was degassed and stored over 4 Å molecular sieves in an AcrosSeal® bottle.…”

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

confidence: 99%

“…To this end, we reasoned that if single electron transfer (SET) to the metastable silylated hemiaminal or iminium ion could be realized, entry to the nucleophilic α-amino radical and therefore umpolung reactivity would be enabled (Scheme 2). Of the techniques available for such a single electron reduction, photoredox catalysis has emerged as the most versatile, and in related works, 15 the resulting free radical species have been shown to engage in a range of transformations, including reaction with electrophilic species such as Michael acceptors. 16 Scheme 2.…”

Section: Introductionmentioning

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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Dearomative Photocatalytic Construction of Bridged 1,3‐Diazepanes

Cited by 75 publications

References 138 publications

Dual emission in purely organic materials for optoelectronic applications

Dual emission in purely organic materials for optoelectronic applications

Dearomative Photocatalytic Construction of Bridged 1,3-Diazepanes

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

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