Catalytic Enantioselective Reaction of 2<i>H</i>-Azirines with Thiols Using Cinchona Alkaloid Sulfonamide Catalysts

Nakamura, Shuichi; Hayama, Daiki; Miura, Makiko; Hatanaka, Tsubasa; Funahashi, Yasuhiro

doi:10.1021/acs.orglett.7b04022

Cited by 42 publications

(16 citation statements)

References 59 publications

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“…[24] Nakamura et al applied the enantioselective reaction of thiols with 2H-azirines to in-situ-prepared ethyl 2H-azirine-3carboxylate (37), as ap recursor to a-/b-aminoacid esters, by using 8-quinolinesulfonylated cinchonidine catalyst 39 to afford products (R)-38 in good yields with high enantioselectivities (Scheme 13). [25] Furthermore, the reaction of 2H-azirines 37 with thiols by using 8-quinolinesulfonamide catalyst 40, which was prepared from cinchonine, afforded the opposite enantiomer with good enantioselectivities (up to 94 % ee). Good enantioselectivity was still obtained, even when the catalyst loading was decreased to 0.5 mol %( 93 % ee).…”

Section: Nucleophilicaddition Reactionsmentioning

confidence: 99%

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: Nucleophilicaddition Reactionsmentioning

confidence: 99%

Enantioselective Reaction of 2H‐Azirines

Nakamura

2019

Chemistry An Asian Journal

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“…[10] Notably,N akamura and co-workersr eported that the organocatalyst (8-quinolinesulfonamide) catalyzed the addition of thiols to 2H-azirines to produce chiral aziridines with high enantioselectivities (Scheme 1E). [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.…”

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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“…The addition of nucleophiles to the CN double bond of azirines serves as a convenient entry to C-substituted N–H aziridines . A plethora of nucleophiles have been reported to add to azirines, including organolithiums, Grignard reagents, N–H compounds, , phosphites, thiols, TMSCF 3 , TMSCN, , and hydride . Given this excellent demonstrated reactivity of azirines, we reasoned that carbamoyl anions should also add readily to the strained heterocycles to provide 2-aziridinyl amides (Figure D).…”

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confidence: 99%

Carbamoyl Anion Addition to Azirines

et al. 2021

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The addition of carbamoyl anions to azirines affords synthetically useful 2-aziridinyl amide building blocks. The reaction scope was explored with respect to both formamide and azirine, and the addition was found to be highly diastereoselective. A one-pot conversion of a ketoxime to an aziridinyl amide was demonstrated. The method was employed to incorporate an aziridine residue into a dipeptide segment.

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Catalytic Enantioselective Reaction of 2H-Azirines with Thiols Using Cinchona Alkaloid Sulfonamide Catalysts

Cited by 42 publications

References 59 publications

Enantioselective Reaction of 2H‐Azirines

Enantioselective Reaction of 2H‐Azirines

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

Carbamoyl Anion Addition to Azirines

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