Asymmetric Aziridination of <i>N</i>-Sulphonyl Ketimines with Unfunctionalized Ketones: A One-pot Approach to Multisubstituted Fused Aziridines

Zhang, Sheng; Li, Lijun; Xin, Lilan; Liu, Wenmin; Xu, Kun

doi:10.1021/acs.joc.6b02827

Cited by 30 publications

(9 citation statements)

References 56 publications

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“…Moreover, the catalytic reactions worked well for the cyclic aldimines 5′ when employing the α‐chloro acetophenones 6′ as nucleophilic reaction partners, giving products ( 8 a – f ) with excellent stereoselectivities in high yields. The X‐ray crystal structure of rac ‐ 7 a was obtained, and the absolute configurations of the aza‐Darzens products listed in Table were assigned by comparing both the optical rotation and HPLC analysis of 7 a′ with that of previously reported results …”

Section: Methodsmentioning

confidence: 99%

Highly Enantioselective Synthesis of Fused Tri‐ and Tetrasubstituted Aziridines: aza‐Darzens Reaction of Cyclic Imines with α‐Halogenated Ketones Catalyzed by Bifunctional Phosphonium Salt

Pan

Zhang

et al. 2019

Angew Chem Int Ed

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The first enantioselective aza-Darzens reaction of cyclic imines with a-halogenated ketones was realized under mild reaction conditions by using amino-acid-derived bifunctional phosphonium salts as phase-transfer promoters.A variety of structurally dense tri-and tetrasubstituted aziridine derivatives,c ontaining benzofused heterocycles as well as spiro-structures,w ere readily synthesized in high yields with excellent diastereo-and enantioselectivities (up to > 20:1 d.r. and > 99.9 %ee). The highly functionalizedaziridine products could be easily transformed into different classes of biologically active compounds.Optically pure fused N-heterocycles,e specially aziridinecontaining molecules,are versatile intermediates in chemical synthesis, [1] and they are also prevalent building blocks in many biologically active compounds,i ncluding natural alkaloids and pharmaceutical agents (Scheme 1). [2] Accordingly, an umber of catalytic methods have been devised for the stereoselective construction of such structural motifs over the past two decades. [3][4][5][6][7][8][9] In this context, the aza-Darzens reaction becomes one of the most straightforward and efficient approaches for producing such ring systems. [5] Lewis and Brønsted acid catalyzed aza-Darzens of a-diazoacetates and imines,offering aziridines,were first disclosed by Brookhart, Te mpleton, and co-worker. [6] Thea symmetric variants of these acid-catalyzed aza-Darzens reactions were first reported by Wulff and co-workers [7] and further developed by Maruoka and co-workers, [8] and others, [9] particularly providing cis-o r/and trans-disubstituted aziridines in high yields with excellent stereoselectivities.However,less success has been achieved in direct construction of trisubstituted chiral aziridine scaffolds by this process,a nd only two examples were reported. [10] Maruoka and co-workers dis-closed achiral Brønsted acid catalyzed aziridination between N-a-diazoacylo xazolidinones and N-Boc imines,t hus creating trisubstituted chiral aziridine skeletons. [10a] Quite recently, Tr ost developed aZ n-ProPhenol catalyzed aza-Darzens reaction of chlorinated aromatic ketones with N-Boc aldimines,p roviding an ovel method for constructing trisubstituted chiral aziridine motifs. [10b] Although these impressive advances have been made,h ighly enantioselective preparation of trisubstituted aziridine rings is still synthetically challenging,let alone direct asymmetric synthesis of structurally dense tetrasubstituted chiral aziridine molecules.T ot he best of our knowledge,n og eneral and straightforward catalytic protocol to access optically pure tetrasubstituted aziridines has been reported so far. Therefore,i ti sh ighly desirable to explore autilitarian strategy to fill this void.In this study,w ea ttempted to develop an alternative approach to prepare structurally dense tri-and tetrasubstituted aziridines with readily available catalysts and reagents. In the past decades,a symmetric phase-transfer catalysis (PTC) has been recognized as ap owerful and versatile...

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Section: Methodsmentioning

confidence: 99%

Highly Enantioselective Synthesis of Fused Tri‐ and Tetrasubstituted Aziridines: aza‐Darzens Reaction of Cyclic Imines with α‐Halogenated Ketones Catalyzed by Bifunctional Phosphonium Salt

Pan

Zhang

et al. 2019

Angew Chem Int Ed

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“…To this end, the first scaffold target was the smallest stable aza‐ring system, that is, aziridines . Among different possible synthetic strategies to aziridines, the carbenium transfer approach through sulfonium ylides was employed affording different aziridine‐fused sulfonamides ( 2 a – h ) with two different sites in acceptable to good yields (Scheme ). Intriguingly, reactions of sulfonium ylides with N‐sulfonyl‐aldimine 1 (R 1 =H) did not afford the corresponding aziridines.…”

Section: Methodsmentioning

confidence: 99%

“…To this end, the first scaffold target was the smallest stable aza-ring system, that is, aziridines. [6] Among differentp ossible synthetic strategies to aziridines, [7] the carbenium transfer approacht hrough sulfonium ylides was employed affording different aziridine-fused sulfonamides (2a-h) with two differents ites in acceptable to good yields (Scheme2). Intriguingly,r eactions of sulfonium ylides with Nsulfonyl-aldimine 1 (R 1 = H) did not afford the corresponding aziridines.E xcept for 2c and 2h that bear two adjacent aryl groups,a nd were formed in equimolar ratio of syn and anti isomersi nh igh yields, aziridines were formed mostly as single syn diastereomers (2b, 2d-g)o ra sm ajor isomer (2a,d .r.7 :1).…”

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confidence: 99%

A Scaffold‐Diversity Synthesis of Biologically Intriguing Cyclic Sulfonamides

Zimmermann

Akbarzadeh

Otte

et al. 2019

Chemistry A European J

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A" branching-folding" synthetic strategy that affords arange of diversecyclic benzo-sulfonamide scaffolds is presented. Whereasd ifferent annulation reactions on common ketimine substrates build the branching phase of the scaffold synthesis, ac ommon hydrogenative ringexpansion method, facilitated by an increase of the ringstrain during the branching phase, led to sulfonamides bearingm edium-sized rings in af olding pathway.C ell paintinga ssay was successfullye mployed to identify tubulin targeting sulfonamides as novel mitotic inhibitors. Supporting information and the ORCID identification number(s) for the author(s) of this articlecan be found under: https://doi.org/10.Scheme2.Abranching pathwaytoc yclic sulfonamides by annulationa nd addition reactions of N-sulfonyl ketimines. DABCO = 1,4-diazabicyclo[2.2.2]octane.Scheme3.Ring-expansion and modulationr eactions through palladium-mediatedheterogeneoush ydrogenation/hydrogenolysis.Conditions:i )10mol %P d/ C, EtOH/EtOAc,1 atm H 2 ;ii) 14 mol %P d/C, EtOH/EtOAc, 7.5 atm H 2 ;i ii)Pearlman'sc atalyst (20 wt %.,9mol %), MeOH/EtOAc,2h; iv) aq. NaOH/THF/MeCN, 19 h; v) first,( COCl) 2 or SOCl 2 in CHCl 3 ,6 08C; then, corresponding amine in THF at 0 8C; vi)Pd(OH) 2 /C, H 2 ;v ii)10mol %P d/C, 7atm H 2 ,16h;v iii)Et 3 N, CDI, MeCN,1 6h;ix) 10 mol %P d/CH 2 ,EtOH (+ EtOAc for 22 d). For 22a:a dditional step of DMP/NaHCO 3 ,DCM 08 C, 3h;x )NaB(OAc) 3 H, corresponding amine, 4 MS, 1,2-DCE,16-48h.

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“…In 2017, Xu, Zhang and co‐workers presented a highly diastereo‐ and enantioselective one‐pot procedure for the preparation of multisubstituted chiral fused aziridines 71 that consisted of an amino amide Cat. 24 ‐catalyzed direct asymmetric Mannich reaction of 2b with unmodified ketones 7 and a CuBr 2 ‐promoted oxidative intramolecular C–H amination reaction . Notably, the iodinated product 73 was generated instead as a single diastereomer in the absence of transition metal salts, albeit in a low yield (Scheme ).…”

Section: Use Of Cyclic Imines 2 Bearing a 1h‐isoindole Moietymentioning

confidence: 99%

Organocatalytic Asymmetric Transformations Involving the Cyclic Imine Moiety in Indole and Isoindole Related Heterocycles

Cheng

Shao

2018

Adv Synth Catal

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Scheme 8. Asymmetric Mannichr eaction of 2-aryl-3H-indol-3-ones 1c with aldehydes and ketones catalyzed by l-proline. Scheme 12. Catalytic asymmetric aza-DAr eaction of 2-aryl-3H-indol-3-ones 1c with 2,4-dienals 34 via trienaminec atalysis. Scheme 18. Enantioselective[ 4 + +2] cycloaddition of ketimines 2a or 2b with allenoate 53a catalyzed by (R)-SITCP Cat. 18. Scheme 34. Bifunctional phosphine Cat. 31-catalyzed stepwise [4+ +2]/[2+ +2] cycloadditions between allene ketones 96 and 2d.

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Asymmetric Aziridination of N-Sulphonyl Ketimines with Unfunctionalized Ketones: A One-pot Approach to Multisubstituted Fused Aziridines

Cited by 30 publications

References 56 publications

Highly Enantioselective Synthesis of Fused Tri‐ and Tetrasubstituted Aziridines: aza‐Darzens Reaction of Cyclic Imines with α‐Halogenated Ketones Catalyzed by Bifunctional Phosphonium Salt

Highly Enantioselective Synthesis of Fused Tri‐ and Tetrasubstituted Aziridines: aza‐Darzens Reaction of Cyclic Imines with α‐Halogenated Ketones Catalyzed by Bifunctional Phosphonium Salt

A Scaffold‐Diversity Synthesis of Biologically Intriguing Cyclic Sulfonamides

Organocatalytic Asymmetric Transformations Involving the Cyclic Imine Moiety in Indole and Isoindole Related Heterocycles

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