An unexpected benzylic oxidation in the multicomponent synthesis of simplified analogs of anchinopeptolides and eusynstyelamides

Capurro, Pietro; Bergamaschi, Enrico; Basso, Andrea; Moni, Lisa

doi:10.1007/s10593-020-02682-9

Cited by 3 publications

(4 citation statements)

References 10 publications

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“…This was achieved via synthesis of the 2-(trimethylsilyl)ethane sulfonamide (SES) analogue of the isoindoline 4c , which could either be oxidized to the isoindole 5c and then deprotected or be directly converted to the free isoindole 5g using tetrabutylammonium fluoride (TBAF), which was more efficient and higher yielding (Scheme ). The exact mechanism of oxidation in the presence of TBAF is yet to be determined. , Upon removal of the SES protecting group, the methylene groups have singlet 1 H NMR resonances, indicating that the methylene protons are no longer diastereotopic. Although it is possible that diastereotopic splitting may be elucidated at lower temperatures to reveal latent atropisomerism, the lack of such splitting at room temperature classifies the deprotected 5g as a Class 1 system, nonatropisomeric.…”

Section: Resultsmentioning

confidence: 99%

“…The exact mechanism of oxidation in the presence of TBAF is yet to be determined. 76,77 Upon removal of the SES protecting group, the methylene groups have singlet 1 H NMR resonances, indicating that the methylene protons are no longer diastereotopic. Although it is possible that diastereotopic splitting may be elucidated at lower temperatures to reveal latent atropisomerism, the lack of such splitting at room temperature classifies the deprotected 5g as a Class 1 system, nonatropisomeric.…”

Section: δG ‡mentioning

confidence: 99%

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Synthesis and Atropisomeric Properties of Benzoazepine-Fused Isoindoles

et al. 2023

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Atropisomeric, bench-stable benzoazepine-fused isoindoles were synthesized via oxidation from isoindoline precursors. Using the isoindoles 5d−f as models, the stereochemistry and conformational folding of the systems were examined. Chiral UHPLC was used to analyze the rate of racemization and calculate the Gibbs free energy of enantiomerization (ΔG ‡ Enant ). X-ray crystallography, 1 H NMR spectroscopy, and DFT calculations were used to elucidate the three axes of chirality and clarify the structural factors contributing to ΔG ‡ Enant . Tandem rotation around the axes of chirality precludes the formation of diastereomers, with rotational restriction of the C aryl −N sulfonamide bond determined as the moderator of atropisomeric stability in the system, affected primarily by steric hindrance as well as by π-stacking interactions facilitated by the folded conformation of the sulfonamide over the isoindole moiety. Article pubs.acs.org/joc

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Section: Resultsmentioning

confidence: 99%

Section: δG ‡mentioning

confidence: 99%

Synthesis and Atropisomeric Properties of Benzoazepine-Fused Isoindoles

et al. 2023

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“…α-Substituted acrylamides 2 have been demonstrated to be valuable synthons for the synthesis of heterocycles 12 and natural products. 13 Having established this new methodology, we then moved to explore the possibility to couple the multicomponent reactions with visible-light-mediated functionalization of the resulting products. The first reaction we explored was a trifluoromethylation, which was first attempted on substrate 2f with trifluoromethylsulfonyl chloride in the presence of eosin Y under green LED irradiation, unsuccessfully; eventually, the synthesis of 3 was achieved using Umemoto II reagent and Ru photoredox catalysis with blue light, both in batch and under continuous flow conditions ( Scheme 3 , top).…”

Section: Resultsmentioning

confidence: 99%

“…α-Substituted acrylamides 2 have been demonstrated to be valuable synthons for the synthesis of heterocycles and natural products . Having established this new methodology, we then moved to explore the possibility to couple the multicomponent reactions with visible-light-mediated functionalization of the resulting products.…”

Section: Resultsmentioning

confidence: 99%

Into the Blue: Ketene Multicomponent Reactions under Visible Light

et al. 2021

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For the first time, a detailed study on the photophysical properties of variously substituted diazoketones and on their photoreactivity under blue LED irradiation was carried out. Despite very limited absorbance in the visible region, we have demonstrated that, independently from their structure, α-diazoketones all undergo a very efficient Wolff rearrangement. Contrarily to the same UV-mediated reaction, where photons can give rise to side processes, in this case, almost all absorbed photons are selective and effective, and the quantum yield is close to 100%. If the rearrangement is carried out in the presence of isocyanides and carboxylic acids/silanols, the photoreactivity is not affected, and the resulting ketenes can afford α-acyloxy- and α-silyloxyacrylamides through two distinct multicomponent reactions, performed both in batch and under continuous flow, with improved selectivity and broader scope. These photoinduced multicomponent reactions can be coupled with other visible-light-mediated transformations, thus increasing the diversity of the molecules obtainable by this approach.

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