Homoallyllic Nitrone Isomerization: Convenient Enantioselective Synthesis of Homoallylic Nitrones and Homoallylic Hydroxylamines

Cheng, Hin‐Soon; Seow, Ai-Hua; Loh, Teck‐Peng

doi:10.1021/ol800925v

Cited by 16 publications

(7 citation statements)

References 20 publications

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“…In the particular case of a-N-homoallylamino nitriles, a subsequent aza-Cope rearrangement takes place to afford previously unreported (2-azoniaallyl)zinc intermediates, [50] which lead to 2,3-methanopyrrolidines after a [3 + 2] cycloaddition process. Remarkable features of this mechanism include a chirality transfer through an asymmetric aza-Cope rearrangement, which is rather uncommon, [51] and the formation of a metalated azomethine-ylide that is configurationally stable on the timescale of the subsequent reaction. Additional mechanistic studies are underway in our group to fully understand the [3 + 2] process and will be reported in due course.…”

Section: Resultsmentioning

confidence: 99%

Cyclization of Zincated α‐N‐Homoallylamino Nitriles: A New Entry to Enantiopure 2,3‐Methanopyrrolidines

Ouizem

Cheramy

Botuha

et al. 2010

Chemistry A European J

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Stereoselective cyclization of zincated α-N-homoallylamino nitriles has been developed. Following treatment with lithium diisopropylamide (LDA) and transmetalation with zinc bromide, α-N-(1-phenylethyl)-N-homoallylamino nitriles lead to 2,3-methanopyrrolidines in moderate to good yields (up to 66 %) and excellent selectivities (up to >98:2). With substrates derived from α-branched homoallylic amines, a stereospecific inversion of the homoallylic stereogenic center was observed. To account for this, a mechanistic rationale involving the formation of zincioiminium ions from zincated α-amino nitriles is put forward. 2,3-Methanopyrrolidines should then arise from a sequence involving an aza-Cope rearrangement providing a configurationally stable (2-azoniaallyl)zinc species that then undergoes a [3+2] cycloaddition reaction.

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Section: Resultsmentioning

confidence: 99%

Cyclization of Zincated α‐N‐Homoallylamino Nitriles: A New Entry to Enantiopure 2,3‐Methanopyrrolidines

Ouizem

Cheramy

Botuha

et al. 2010

Chemistry A European J

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“…Wuts and Jung reported the 2‐aza‐Cope rearrangement of nitrones under catalysis with trimethylsilyl triflate,16 which actually involves hydroxyiminium cations. A similar process was described twenty years later by Loh and co‐workers using 10‐camphorsulfonic acid (CSA) as a catalyst 17. In both cases, the rearrangement involved cationic species, as in other 2‐aza‐Cope rearrangements.…”

Section: Introductionmentioning

confidence: 71%

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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“…84 Homoallylic nitrones are prepared from homoallylic hydroxylamines and aldehydes upon treatment with (+)-10-camphorsulfonic acid (CSA) catalyst via the 2-oxonia- [3,3]-sigmatropic rearrangement regioselectively (eq 16). 85 N-Vinylnitrones have been prepared by a two-step method; the reactions of αchloroaldehyde or α-phenoxyor α-acetoxyketone with Nbenzylhydroxylamines followed by treatment with a base (eq 17). 86 Oxazoline N-oxides (eq 18) 87 and imidazoline N-oxides 88 are obtained by condensations of heteroatom-substituted hydroxylamines with orthoesters.…”

Section: Oxidation Reactionmentioning

confidence: 99%

Synthesis and Transformations of Nitrones for Organic Synthesis

2019

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Nitrones are important compounds and are highly useful in many aspects. The first part describes the methods for synthesis of nitrones, which are useful and environmentally friendly. Catalytic oxidations, condensations, and other useful reactions are described. The nitrones thus obtained are key intermediates for the synthesis of biologically important nitrogen compounds. The second part describes the fundamental transformations of nitrones, which will provide the strategies and means for the construction of nitrogen compounds. The reactions with nucleophiles or radicals, C–H functionalization, and various addition reactions are described. The last reactions are particularly important for highly selective carboncarbon bond formations. 1,3-Dipolar cycloaddition reactions are excluded because the size of the review is limited and excellent reviews have been published in Chemical Reviews.

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Homoallyllic Nitrone Isomerization: Convenient Enantioselective Synthesis of Homoallylic Nitrones and Homoallylic Hydroxylamines

Abstract: An alpha-regioselective synthesis of homoallylic nitrones from aldehydes is reported on the basis of [3,3]-sigmatropic rearrangement. The products are obtained in up to 99% enantioselectivity and up to 80% yield under environmentally benign and mild reaction conditions.

Cited by 16 publications

References 20 publications

Cyclization of Zincated α‐N‐Homoallylamino Nitriles: A New Entry to Enantiopure 2,3‐Methanopyrrolidines

Cyclization of Zincated α‐N‐Homoallylamino Nitriles: A New Entry to Enantiopure 2,3‐Methanopyrrolidines

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

Synthesis and Transformations of Nitrones for Organic Synthesis

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