Catalytic Enantioselective Aza‐Benzoin Reactions of Aldehydes with 2<i>H</i>‐Azirines

Peng, Qiupeng; Guo, Donghui; Bie, Jianbo; Wang, Jian

doi:10.1002/anie.201712785

Cited by 45 publications

(21 citation statements)

References 68 publications

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“…Wang and co‐workers reported the first successful catalytic asymmetric reaction of carbon nucleophiles with 2 H ‐azirines (Scheme ) . The umpolung reaction of aldehydes 48 with 2 H ‐azirines 47 in the presence of a chiral N ‐heterocyclic carbene (NHC) as a catalyst underwent an aza‐benzoin reaction through a Breslow intermediate .…”

Section: Enantioselective Reactions Of 2h‐azirinesmentioning

confidence: 99%

“…Wang and co-workers reported the first successful catalytic asymmetricr eaction of carbon nucleophilesw ith 2H-azirines (Scheme 16). [26] The umpolung reactiono fa ldehydes 48 with 2H-azirines 47 in the presence of ac hiral N-heterocyclic car-Scheme12. Proposed transition state in the reaction of 2H-azirine 25 with diphenyl phosphite 26 by using bis(imidazoline)(28)-phenol as ac atalyst.…”

Section: Nucleophilicaddition Reactionsmentioning

confidence: 99%

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Enantioselective Reaction of 2H‐Azirines

Nakamura

2019

Chemistry An Asian Journal

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2H‐Azirines are useful precursors for the synthesis of a variety of chiral aziridine and amine derivatives with a range of biological activities. Owing to the ring strain and the presence of a C=N double bond, 2H‐azirines are more reactive than other types of ketimine, and undergo a range of enantioselective reactions, including reduction and Diels–Alder reactions, as well as nucleophilic addition to the C=N double bond. Therefore, the enantioselective reactions of 2H‐azirines has become a hot topic, in particular within the last few years. In this Minireview, we focus on the enantioselective reactions of 2H‐azirines by using catalytic or stoichiometric amounts of chiral additives, the reaction mechanisms, and the applications of these reactions of 2H‐azirines and related compounds in organic synthesis.

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Section: Enantioselective Reactions Of 2h‐azirinesmentioning

confidence: 99%

Section: Nucleophilicaddition Reactionsmentioning

confidence: 99%

Enantioselective Reaction of 2H‐Azirines

Nakamura

2019

Chemistry An Asian Journal

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“…An unprecedented enantioselective aza-benzoin coupling, starting from ring-strained 2H-azirines and aromatic aldehydes to give chiral aziridines, useful building synthons and valuable pharmaceutical structural motifs has been recently reported [38]. Functionalized benzaldehydes and heteroaromatic aldehydes are well tolerated (Scheme 21).…”

Section: Scheme 20mentioning

confidence: 99%

“…Scheme 21. Selected examples of enantioselective intermolecular aza-benzoin reactions between aldehydes and 2H-azirines from Ref [38].…”

Section: Scheme 20mentioning

confidence: 99%

An Overview on the N-Heterocyclic Carbene-Catalyzed Aza-Benzoin Condensation Reaction

Albanese

Gaggero

2018

Catalysts

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Abstract:The N-heterocyclic carbene(NHCs)-catalyzed aza-benzoin condensation reaction is an efficient, single step strategy which employs easily available substrates, such as aldehydes and imines, to provide α-amino ketones. The multifunctionality and high reactivity of α-amino ketones makes these structures attractive for medicinal chemistry and as precursors of a variety of amine derivatives. The different electrophilic characteristics of aldehydes and imines ensure a high regioselective reaction. Enantiomerically-enriched α-amino ketones have been synthesized through stereoselective couplings promoted by chiral N-heterocyclic carbenes. One-pot domino procedures, including an aza-benzoin step, allow valuable complex molecules to be accessed.

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“…[11] In 2018, Peng and co-workers reported the N-heterocyclic carbene( NHC)-catalyzed asymmetric addition of aldehydes to the C=Nbond of 2H-azirines. [12] The above two organocatalysts are very efficient and convenient for promoting the formation of chiral aziridines and shouldp lay similarr oles in asymmetric additionstothe C=N bond of 2H-azirines. Therefore, exploring the general role of organocatalysts and predicting the origin of reactione nantioselectivity are highly desirable.…”

Section: Introductionmentioning

confidence: 99%

Insights into N‐Heterocyclic Carbene (NHC)‐Catalyzed Asymmetric Addition of 2H‐Azirine with Aldehyde

Liu

Sun²,

et al. 2019

Chemistry An Asian Journal

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The possible mechanisms and origin of the enantioselectivity of the reaction between 2H-azirine and an aldehyde catalyzed by an N-heterocyclic carbene (NHC) were theoretically studied and predicted at the M06-2X/6-31G(d,p)/IEF-PCM MTBE //M06-2X-GD3/6-311 ++G(2df, 2pd)/ IEF-PCM MTBE level. The mostf avorable reaction pathway consists of four steps, i.e.,c omplexation of the NHC and the aldehyde, stepwise [1,2]-proton transfer,C ÀCb ond formation coupled with another proton transfer,a nd recycling of the NHC. The computational resultsi ndicate that the stereoselectivity-determining step is also the rate-determinings tep, which is the third step (i.e.,i ntermolecular addition). The calculated 99 % ee is very close to the experimentally observed value of 96 % ee,demonstrating that the calculations are reliable. Twoi mportant roles of the NHC were identifiedb y global reactioni ndex (GRI) analysisa nd natural population analysis( NPA), that is, realizing the umpolung reactivity of the aldehyde and facilitating the deprotonation of aldehyde. Moreover,t he efficiency of different NHC catalysts can be mainly predicted by computing the nucleophilic index of the corresponding Breslow intermediates. Furthermore, distortion/interaction and noncovalenti nteraction (NCI) analyses revealed that the p···p interactions between the NHC and substrates were the key factor in the reaction enantioselectivity.Scheme1.Asymmetric additions to the C=Nb ond of 2H-azirines for the synthesis of chiral aziridines under different transitionmetal-andorganocatalyst-catalyzed conditions.Scheme2.The entire catalytic cycle of the title reaction.

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Catalytic Enantioselective Aza‐Benzoin Reactions of Aldehydes with 2H‐Azirines

Cited by 45 publications

References 68 publications

Enantioselective Reaction of 2H‐Azirines

Enantioselective Reaction of 2H‐Azirines

An Overview on the N-Heterocyclic Carbene-Catalyzed Aza-Benzoin Condensation Reaction

Insights into N‐Heterocyclic Carbene (NHC)‐Catalyzed Asymmetric Addition of 2H‐Azirine with Aldehyde

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