Sequential Nucleophilic Addition/Intramolecular Cycloaddition to Chiral Nonracemic Cyclic Nitrones: A Highly Stereoselective Approach to Polyhydroxynortropane Alkaloids

Delso, J. Ignacio; Tejero, Tomás; Goti, Andrea; Merino, Pedro

doi:10.1021/jo200315k

Cited by 45 publications

(16 citation statements)

References 42 publications

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“…Nitrone 3 was prepared with complete selectivity and quantitative yield from nitrone 12 ,20a which was obtained from D ‐arabinose in six steps and 21.8 % overall yield (Scheme ) 27…”

Section: Resultsmentioning

confidence: 99%

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Evasive Neutral 2‐Aza‐Cope Rearrangements. Kinetic and Computational Studies with Cyclic Nitrones

et al. 2013

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A full experimental study of the activation energy required for the hitherto unknown neutral 2‐aza‐Cope rearrangement is presented. A kinetic study of the process showed activation energies in the range of 22.91–24.06 kcal/mol, in agreement with a process operating at moderate temperature (70 °C). Calculations at B3LYP/6‐311+G(d,p) and M06‐2X/6‐311+G(d,p) levels of theory considering solvent (dimethyl sulfoxide (DMSO) and toluene) effects (PCM model) predict reaction energy barriers that are in agreement with the values obtained from 1H NMR‐based kinetic experiments. Results obtained by using enantiomerically pure substrates demonstrate that the rearrangement takes place with complete transfer of chirality, in contrast to previously described cationic processes. The effects of solvent and acid catalysis, which converts the process into the more common cationic rearrangement, have also been studied. DFT calculations also predict correctly the acceleration of the process under acid catalysis, estimating energy barriers in the range of 16.80–18.57 kcal/mol.

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“…Nitrone 3 was prepared with complete selectivity and quantitative yield from nitrone 12 ,20a which was obtained from D ‐arabinose in six steps and 21.8 % overall yield (Scheme ) 27…”

Section: Resultsmentioning

confidence: 99%

“…On the other hand, nitrone 17 was obtained from nitrone 3 in quantitative yield and complete selectivity under the same reaction conditions. Prolonged heating of isolated 17 (or directly from 3 ) ultimately led to the corresponding cycloadduct 18 , as described 20a…”

Section: Resultsmentioning

confidence: 99%

Evasive Neutral 2‐Aza‐Cope Rearrangements. Kinetic and Computational Studies with Cyclic Nitrones

et al. 2013

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“…The addition of allylmagnesium bromide to cyclic nitrones 36 and 37 has been used in the synthesis of calystegines [55] and closely related nortropane alkaloids [56]. In these cases, excelent selectivities were observed with the employed substrates (Scheme 10); in general very good diastereofacial selectivities were obtained in the allylation of ppolyhydroxylated cyclic nitrones.…”

Section: Methodsmentioning

confidence: 99%

Recent Advances in the Preparation of Enantiomerically Pure Hydroxylamines from Nitrones

Matute¹,

García‐Viñuales²,

Hayes³

et al. 2016

COS

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This review covers the recent advances in the synthesis of enantiomerically pure hydroxylamines employing nitrones as starting materials. Nucleophilic additions of organometallic reagents to nitrones are the most common way for introducing a hydroxyamino group into carbon skeletons with the concomitant formation of a new carbon-carbon bond. Addition of carbanions derived from enolates, cyanide or fluorinated derivatives allow the preparation of complex structures. Radical additions and, in particular samarium diiodide-mediated reductive coupling of nitrones with carbonyl compounds and α,β-unsaturated esters have also been considered. All these approaches provide efficient methods of preparation of enantiomerically pure hydroxylamienes that are valuable synthetic intermediates. KeywordsHydroxylamines; Nitrones; Organometallics; Mannich; Reductive coupling 2 Graphical Abstract 3

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“…In contrast to aldonitrones, which have been widely used in synthesis, cyclic ketonitrones have been studied much less, even though they could give access to original alkaloid‐like structures containing a quaternary centre in the position α to the nitrogen atom , . To the best of our knowledge, these compounds have never been used in cycloaddition reactions to target pyrrolizidines and indolizidines.…”

Section: Introductionmentioning

confidence: 99%

“…To the best of our knowledge, these compounds have never been used in cycloaddition reactions to target pyrrolizidines and indolizidines. The design of synthetic routes towards such alkaloids bearing a quaternary centre at the ring junction seemed highly desirable, especially in view of recent reports describing polyhydroxylated nortropanes,[7b] indolizidines,[7c] and quinolizidines[7d] substituted at the ring junction as exceptionally potent and selective inhibitors of α‐glucosidases.…”

Section: Introductionmentioning

confidence: 99%

Ring‐Junction‐Substituted Polyhydroxylated Pyrrolizidines and Indolizidines from Ketonitrone Cycloadditions

et al. 2018

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A 1,3‐dipolar cycloaddition reaction of carbohydrate‐derived five‐membered cyclic ketonitrones with alkynes and alkenes was developed as an efficient and regioselective process to access highly functionalised isoxazolines and isoxazolidines bearing a quaternary centre α to the nitrogen atom. The latter compounds were used as intermediates for the synthesis of unprecedented ring‐junction‐substituted polyhydroxylated pyrrolizidines and indolizidines. These compounds were evaluated against a panel of glycosidases, and showed moderate but selective inhibition of α‐glucosidases.

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Sequential Nucleophilic Addition/Intramolecular Cycloaddition to Chiral Nonracemic Cyclic Nitrones: A Highly Stereoselective Approach to Polyhydroxynortropane Alkaloids

Cited by 45 publications

References 42 publications

Evasive Neutral 2‐Aza‐Cope Rearrangements. Kinetic and Computational Studies with Cyclic Nitrones

Evasive Neutral 2‐Aza‐Cope Rearrangements. Kinetic and Computational Studies with Cyclic Nitrones

Recent Advances in the Preparation of Enantiomerically Pure Hydroxylamines from Nitrones

Ring‐Junction‐Substituted Polyhydroxylated Pyrrolizidines and Indolizidines from Ketonitrone Cycloadditions

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