Intermolecular [2 + 2] Cycloaddition of 1,4-Dihydropyridines with Olefins via Energy Transfer

Wang, Chengfeng; Lu, Zhan

doi:10.1021/acs.orglett.7b02881

Cited by 43 publications

(19 citation statements)

References 44 publications

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“…Toluene was degassed and stored over 4 Å molecular sieves in an AcrosSeal® bottle. (19) Dialkyl and benzyl-substituted amides were found to be incompatible with these reaction conditions (see supporting information). (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.…”

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

confidence: 96%

“…Preliminary 19 F NMR studies were performed using the model substrate 1a in order to establish reference peaks for the starting material, the hemiaminal intermediate and possible over-reduction and hydrolysis side products for the following optimisation efforts. In an oven-dried NMR tube, purged with N2, the amide 1a (28 mg, 0.125 mmol) and IrCl(CO)(PPh3)2 catalyst (Vaska's complex) (2.0 mg, 0.0025 mmol) were dissolved in d2-DCM (0.5 mL).…”

Section: S31 Initial Nmr Studiesmentioning

confidence: 99%

“…TMDS (44 µL, 0.25 mmol) was added and the tube was capped and gently shaken to allow for an evenly diffused solution. 19 F NMR spectrometry experiments were taken after one and two and a half hours respectively. The tube was then allowed to stand overnight and another NMR spectrum was taken.…”

Section: S31 Initial Nmr Studiesmentioning

confidence: 99%

“…An aliquot of the reaction was taken up and analysed using 19 F NMR spectroscopy to directly determine conversion percentage of starting material to the hemiaminal.…”

Section: S311 Procedures For the Optimisation Of The First Reductiomentioning

confidence: 99%

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

confidence: 96%

Section: S31 Initial Nmr Studiesmentioning

confidence: 99%

Section: S31 Initial Nmr Studiesmentioning

confidence: 99%

“…An aliquot of the reaction was taken up and analysed using 19 F NMR spectroscopy to directly determine conversion percentage of starting material to the hemiaminal.…”

Section: S311 Procedures For the Optimisation Of The First Reductiomentioning

confidence: 99%

See 2 more Smart Citations

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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“…Various catalysts were used for the synthesis of these compounds such as ionic liquid (21), tetrabutylammonium hydrogen sulfate (22), I 2 (23), cellulose sulfuric acid (24), HY-Zeolite (25), nano-Fe 3 O 4 (26) nano-Fe 2 O 3 (27), SnCl 4 -functionalized nano-Fe 3 O 4 encapsulated-silica particles (28), ZnFe 2 O 4 nanopowder (29), 3D printed α-Al 2 O 3 (30), Alginic Acid (31), Fe 3 O 4 @SiO 2 (32), magnetic nanoparticle supported Ni 2+ -containing ionic liquid (33) and metal triflate (34). Recently, the direction of science and technology has been shifted towards eco-friendly and natural product resources (such as natural biopolymers) that are attractive candidates in the search for solid support catalysts (24,(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46). Also in recent years, ultrasound has been used to accelerate the chemical reactions proceed via the formation and collapse of transient cavitation bubbles.…”

Section: Introductionmentioning

confidence: 99%

Ultrasound-promoted green synthesis of 1,4-dihydropyridines using fuctionalized MWCNTs as a highly efficient heterogeneous catalyst

Moradi

Zare

2018

Green Chemistry Letters and Reviews

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Carbocycles from Annulation of Alkynes and Alkenes

2022

Addition Reactions With Unsaturated Hydrocarbons

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Intermolecular [2 + 2] Cycloaddition of 1,4-Dihydropyridines with Olefins via Energy Transfer

Cited by 43 publications

References 44 publications

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

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

Ultrasound-promoted green synthesis of 1,4-dihydropyridines using fuctionalized MWCNTs as a highly efficient heterogeneous catalyst

Carbocycles from Annulation of Alkynes and Alkenes

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