Catalytic conversion of conjugated enones into optically active α-keto aziridines using chiral rare earth metal complexes

Sugihara, Hiroyasu; Daikai, Kazuhiro; Jin, Xiu Lan; Furuno, Hiroshi; Inanaga, Junji

doi:10.1016/s0040-4039(02)00361-1

Cited by 49 publications

(16 citation statements)

References 26 publications

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“…[3] However, to our knowledge, a general and highly stereoselective aziridination of simple a,b-unsaturated enones is still lacking. [4,5] Herein, we report an organocatalytic solution to this synthetic problem that is founded upon the use of a readily available chiral primary amine catalyst salt as well as on a rationally designed N-centered nucleophile.Previously reported asymmetric aziridinations of enones have severe restrictions in scope, as only chalcones are suitable substrates: metal-based systems [4] can provide highly enantioenriched compounds protected as N-tosyl derivatives, a protecting group that can prove to be difficult to remove, whereas two ingenious organocatalytic entries to nonprotected aziridines, showing moderate enantioselectivity (up to 67 % ee), were recently reported through the use of chiral tertiary amines. [5] Recently, the spectacular advances achieved in the field of chiral secondary amine catalysis [6] have set the conditions for the development of a highly chemo-and stereoselective aziridination of a,b-unsaturated aldehydes.…”

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“…Previously reported asymmetric aziridinations of enones have severe restrictions in scope, as only chalcones are suitable substrates: metal-based systems [4] can provide highly enantioenriched compounds protected as N-tosyl derivatives, a protecting group that can prove to be difficult to remove, whereas two ingenious organocatalytic entries to nonprotected aziridines, showing moderate enantioselectivity (up to 67 % ee), were recently reported through the use of chiral tertiary amines. [5] Recently, the spectacular advances achieved in the field of chiral secondary amine catalysis [6] have set the conditions for the development of a highly chemo-and stereoselective aziridination of a,b-unsaturated aldehydes.…”

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Organocatalytic Asymmetric Aziridination of Enones

et al. 2008

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The development of novel and efficient catalytic methodologies for the stereoselective preparation of chiral aziridines is an important synthetic target. [1] Aziridines constitute a key structural feature of several classes of natural products and are extremely versatile building blocks that can undergo synthetically useful transformations. [2] The catalytic asymmetric aziridinations of olefins provide direct and useful access to such a valuable scaffold, and great efforts and progress have been made in this field. [3] However, to our knowledge, a general and highly stereoselective aziridination of simple a,b-unsaturated enones is still lacking. [4,5] Herein, we report an organocatalytic solution to this synthetic problem that is founded upon the use of a readily available chiral primary amine catalyst salt as well as on a rationally designed N-centered nucleophile.Previously reported asymmetric aziridinations of enones have severe restrictions in scope, as only chalcones are suitable substrates: metal-based systems [4] can provide highly enantioenriched compounds protected as N-tosyl derivatives, a protecting group that can prove to be difficult to remove, whereas two ingenious organocatalytic entries to nonprotected aziridines, showing moderate enantioselectivity (up to 67 % ee), were recently reported through the use of chiral tertiary amines. [5] Recently, the spectacular advances achieved in the field of chiral secondary amine catalysis [6] have set the conditions for the development of a highly chemo-and stereoselective aziridination of a,b-unsaturated aldehydes. [7] Central to the success of this approach was the ability of the organocatalyst to integrate orthogonal activation modes (iminium ion and enamine catalysis) into a more elaborate reaction sequence, [8] thus promoting first the nucleophilic addition of a N-centered nucleophile followed by an intramolecular cyclization (Scheme 1). We sought to extend this organocatalytic strategy to a,b-unsaturated ketones, an idea that was mainly triggered by the recent applications of chiral primary amine salts as efficient activators of enones through iminium catalysis. [9] The reduced steric constraints of primary amines offers the unique possibility of catalyzing processes between sterically demanding partners, overcoming the inherent difficulties of chiral secondary amine catalysis.In particular, we recently introduced the catalyst primary amine salt 1, [10] which is made by combining the easily available 9-amino(9-deoxy)epi-hydroquinine 2 with d-N-Boc phenylglycine (3; Boc = tert-butyloxycarbonyl). Salt 1 exhibits high reactivity and selectivity in the enantioselective conjugate additions of carbon-, [10a] oxygen-, [10b] and sulfurcentered [10c] nucleophiles to a,b-unsaturated ketones.To consolidate salt 1 as a general and selective iminium catalyst for enones, we questioned whether this catalytic system might be successfully extended to the highly enantioselective amine conjugate addition, a primary strategy for C À N bond construction. [11] Prompted b...

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Organocatalytic Asymmetric Aziridination of Enones

et al. 2008

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“…3,4 However, alkene aziridination, particularly asymmetric aziridination, is far less well developed than the closely related epoxidation. [5][6][7][8] We were attracted by the report of Xu in 2002 that enones can be aziridinated by hydrazinium salt 1 in the presence of NaH (Scheme 1). 9 By analogy with an earlier study, 10 this chemistry was assumed to proceed by deprotonation of 1 to give an N-N ylid (aminimine), which then undergoes Michael addition to the enone followed by ring closure to give the aziridine.…”

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N-Amino-N-methylmorpholinium Salts: Highly Active Aziridination Reagents for Chalcones

Armstrong¹,

Carbery²,

Lamont³

et al. 2006

Synlett

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A highly effective aziridination reagent, based on Nmethylmorpholine, is reported which effects rapid conversion of chalcones to N-unfunctionalised aziridines at room temperature.Aziridines are highly attractive synthetic intermediates, 2 largely because they can undergo ring opening with a variety of nucleophiles to give functionalised amine products. 3,4 However, alkene aziridination, particularly asymmetric aziridination, is far less well developed than the closely related epoxidation. 5-8 We were attracted by the report of Xu in 2002 that enones can be aziridinated by hydrazinium salt 1 in the presence of NaH (Scheme 1). 9 By analogy with an earlier study, 10 this chemistry was assumed to proceed by deprotonation of 1 to give an N-N ylid (aminimine), which then undergoes Michael addition to the enone followed by ring closure to give the aziridine. An advantage of the method is that it affords N-unsubstituted aziridines which allows flexibility in further functionalising the nitrogen with a choice of activating group. We reasoned that this process had potential for asymmetric aziridination if chiral hydrazinium salts were employed. However, the strong base and carcinogenic solvent employed in this work were unattractive, as were the relatively long reaction times. Therefore, we undertook a study of alternative reaction conditions and report here the discovery of two new base systems as well as a more reactive hydrazinium salt that is particularly convenient to prepare. Scheme 1We began by testing the Xu nitrate salt 1 (2 equiv) for aziridination of chalcone with alternative bases and solvents. Early studies showed that it was possible to use NaOH in MeCN, but the yield of aziridine was low (17% after 18 h). Therefore we prepared alternative hydrazinium nitrate salts by amination of several cyclic amines. While the hydrazinium salts derived from N-methylpyrrolidine and N-methylpiperidine gave comparable or lower yields of aziridine, we were delighted to find that the N-methylmorpholinium nitrate salt 2a (Scheme 2), prepared by amination of N-methylmorpholine (Scheme 2), effected aziridination of chalcone in 95% yield after only three hours under the NaOH/MeCN conditions (Scheme 3). While this result was encouraging, particularly in identifying the reactivity of the morpholine framework, we felt that the procedure used to prepare the hydrazinium nitrate salt 2a from N-methylmorpholine was inconvenient since it required reaction with hydroxylamine-O-sulfonic acid (HOSA) and Ba(NO 3 ) 2 over extended time periods at raised temperatures. Therefore, we were pleased to find that the corresponding iodide salt could be more readily prepared simply by treatment of commercially available N-aminomorpholine 3 with one equivalent of iodomethane in THF at 0°C. The hydrazinium iodide salt 2b was isolated after filtration as a white solid in 77% yield and can be further purified by recrystallisation from EtOH. Under the same NaOH/MeCN conditions, the iodide 2b afforded a slightly lower yield of aziridine than nitrate 2a (Schem...

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“…It gave α-ketoaziridines in preparative yields for a large number of aryl or aryl-alkyl enones. [2][3][4] In the reaction performed with chalcone, subsequent isomerization of 2-benzoyl-3-phenylaziridine to α-aminochalcone has been reported. 5 Depending on the nature of the base and the solvent, β-elimination in the primary Michael adduct giving β-aminochalcone was also found to occur.…”

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confidence: 99%

Rearrangement of a 3-acyloxyamino-1,5-diketone into enamine and pyrrole: a mechanistic study

Uncuţa¹,

Bartha²,

Tănase³

et al. 2006

Arkivoc

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The paper reports on the diversity of products obtained from a 3-acyloxyamino-1,5 diketone in reaction with bases, the distribution of products being correlated with the nature of the base and the solvent. Like other derivatives of β-hydroxyamino ketones, this compound reacts to form a 2-acylaziridine. Unusually, however, the aziridine undergoes ring-opening with carbon-carbon bond breaking to yield a β-ketoenaminone as isolable product. A minor path occurring with carbon-nitrogen bond breaking gives an α-acylpyrrole. In a further reaction the ketoenaminone forms a dimer which is characterized by X-ray crystallography.

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Catalytic conversion of conjugated enones into optically active α-keto aziridines using chiral rare earth metal complexes

Cited by 49 publications

References 26 publications

Organocatalytic Asymmetric Aziridination of Enones

Organocatalytic Asymmetric Aziridination of Enones

N-Amino-N-methylmorpholinium Salts: Highly Active Aziridination Reagents for Chalcones

Rearrangement of a 3-acyloxyamino-1,5-diketone into enamine and pyrrole: a mechanistic study

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