Metal-assisted addition of a nitrate anion to bis(oxy)enamines. A general approach to the synthesis of α-nitroxy-oxime derivatives from nitronates

Naumovich, Yana A.; Buckland, Victoria Emily; Sen'ko, Dmitry A.; Nelyubina, Yulia V.; Khoroshutina, Yulia A.; Sukhorukov, Alexey Yu.; Ioffe, Sema L.

doi:10.1039/c6ob00388e

Cited by 27 publications

(11 citation statements)

References 54 publications

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“…These electrophilic reagents are easily accessible by silylation of aliphatic nitro compounds or readily available cyclic nitronates . Owing to the pyramidality of nitrogen and strong π→σ * N−O , n O →σ * N−O interactions, bis(oxy)enamines 1 and 2 can enter S N ′ reactions at the β‐carbon atom with the breakage of one of two weak nitrogen−oxygen bonds (Scheme ) ,. Another electrophilic center in their structure is silicon atom.…”

Section: Introductionmentioning

confidence: 99%

Divergent Reactivity of In Situ Generated Metal Azides: Reaction with N,N‐Bis(oxy)enamines as a Case Study

Zhmurov

Khoroshutina

Новиков

et al. 2017

Chemistry A European J

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What is the most significant result of this study? Non-alkali metal azides are explosive compounds, which can hardly be considered as convenient and useful reagents in organic synthesis. However,a sw ed iscovered in our study the metal ion can modulate the reactivity of the azide anion thus opening new opportunities for the synthesis of organic azides. The compromise is that the use of af ree-metal azide is not needed, since it can be safely generated in solution by ion exchange from NaN 3 and the corresponding metal salt. What was the inspiration for this cover design? The inspiration for the cover picture came from cue sports. We make an analogy of the chemical behavior observed in our studies with ab illiard game, in which balls are ions, and pockets are reac-tive centers of an organic molecule. Unlike in ar eal game based on mechanics, in a" chemical billiard", ion balls after collision may not only bounce off each other,b ut also can fuse to form ac ova-lently bonded pair,w hich moves along its own trajectory.A "metal-ion ball" depending on its nature, directs the attack of the "azide-anion ball" on either one or another electrophilic "pocket" of the substrate (silicon or carbon atoms). Thus, ac hemist is like ap rofessional billiard player selecting the right ball (promoter/cat-alyst) and disposition (reaction conditions) to hit the target center in the molecule. This simple allegory illustrates the results described in our article in ap opular and easy-to-understand manner. What other topics are you working on at the moment? Although we are originally synthetic chemists, our research interests go far beyond the borders of traditional synthesis. Besides our focus on NÀOs ystems and stereoselective synthesis, we are working in the areas of medicinal chemistry,c lick reactions, coordination compounds, polymers and quantum-chemical calculations. Our particular passions are adamantane-like molecules. Among our recent achievements are the synthesis and structural studies of "isourotropine" (the isomer of methenamine) and B,O,N-doped adamantanes. Invited for the cover of this issue is the group of Alexey Sukhorukov at the N. D. ZelinskyI nstitute of Organic Chemistry. The image depicts the reaction pathways taken by metal azides as a" chemical billiard"g ame. Read the full text of the arti

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Section: Introductionmentioning

confidence: 99%

Divergent Reactivity of In Situ Generated Metal Azides: Reaction with N,N‐Bis(oxy)enamines as a Case Study

Zhmurov

Khoroshutina

Новиков

et al. 2017

Chemistry A European J

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“…In a similar fashion, the nitrate anion, in the form of chromium or cobalt nitrate, can be used as a nucleophile [Scheme , Eq. (3)] …”

Section: Nitrones and Nitronates As α‐C‐electrophilic Synthonsmentioning

confidence: 99%

“…The Lewis acid‐mediated functionalization of cyclic nitronates was utilized to access GlaxoSmithKline's potent inhibitors of phosphodiesterase 4 in a stereoselective fashion . In the representative example shown in Scheme , the methyl group in cyclic nitronate 190 was oxygenated by silylation followed by the Cr(III)‐promoted addition of the nitrate anion …”

Section: Applications In Target‐oriented Organic Synthesismentioning

confidence: 99%

“…N‐ Oxyenamine systems can undergo migration of the OR group from the nitrogen atom to a carbon atom. This process readily takes place in N,N ‐bis(oxy)enamines 13 and 15 and is the major side reaction in most transformations of these compounds . For silylated nitrone derivatives (i.e., N‐ siloxyenamines 9 and 11 , Scheme ), no [1,3]‐shift of the siloxy group was observed.…”

Section: Functionalization Of the α‐Carbon Atom In Nitrones And Nitromentioning

confidence: 99%

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C−H Reactivity of the α‐Position in Nitrones and Nitronates

Sukhorukov

2019

Adv Synth Catal

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“…Experimental [20,22] and computational data [22] suggest that the S N ' substitution of the TMSO-group may proceed through an epimerizable N-vinyl,N-oxynitrenium cation C1. In our later study, we were able to optimize the epimerization ratio to 6: 1 by using Cr(NO 3 ) 3 as both a mild Lewis acid and the source of the nitrate anion [20]. However, the yield of nitroxy-derivative 12 was still not very high (ca.…”

Section: Introductionmentioning

confidence: 99%

The Cyclic Nitronate Route to Pharmaceutical Molecules: Synthesis of GSK’s Potent PDE4 Inhibitor as a Case Study

et al. 2020

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An efficient asymmetric synthesis of GlaxoSmithKline’s potent PDE4 inhibitor was accomplished in eight steps from a catechol-derived nitroalkene. The key intermediate (3-acyloxymethyl-substituted 1,2-oxazine) was prepared in a straightforward manner by tandem acylation/(3,3)-sigmatropic rearrangement of the corresponding 1,2-oxazine-N-oxide. The latter was assembled by a (4 + 2)-cycloaddition between the suitably substituted nitroalkene and vinyl ether. Facile acetal epimerization at the C-6 position in 1,2-oxazine ring was observed in the course of reduction with NaBH3CN in AcOH. Density functional theory (DFT) calculations suggest that the epimerization may proceed through an unusual tricyclic oxazolo(1,2)oxazinium cation formed via double anchimeric assistance from a distant acyloxy group and the nitrogen atom of the 1,2-oxazine ring.

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Metal-assisted addition of a nitrate anion to bis(oxy)enamines. A general approach to the synthesis of α-nitroxy-oxime derivatives from nitronates

Cited by 27 publications

References 54 publications

Divergent Reactivity of In Situ Generated Metal Azides: Reaction with N,N‐Bis(oxy)enamines as a Case Study

Divergent Reactivity of In Situ Generated Metal Azides: Reaction with N,N‐Bis(oxy)enamines as a Case Study

C−H Reactivity of the α‐Position in Nitrones and Nitronates

The Cyclic Nitronate Route to Pharmaceutical Molecules: Synthesis of GSK’s Potent PDE4 Inhibitor as a Case Study

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