Rapid Access to Spirocylic Oxindoles: Application of Asymmetric N-Heterocyclic Carbene-Catalyzed [3 + 3] Cycloaddition of Imines to Oxindole-Derived Enals

Xie, Danbo; Yang, Limin; Lin, Youqiang; Zhang, Zhiming; Chen, Dongdong; Zeng, Xiaofei; Zhong, Guofu

doi:10.1021/acs.orglett.5b00726

Cited by 92 publications

(23 citation statements)

References 93 publications

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“…9a We thought that the reaction follows a similar reaction pathway to the literatures. 17 Due to the high leaving ability of the NHPI group on the semi stable ester 1a, the key α,β-unsaturated acyl azolium intermediate I could be easily generated through the addition of the NHC catalyst to the ester (Scheme 4), which would greatly benefit the following steps of the reaction and the stereoselectivity, as proposed by Bode 18 and related literature. 7h Then, a 1,2-addition of the enamine isomerized from imine 2 under basic conditions would occur, after further Claisen rearrangement, tautomerization, and lactam formation transformation sequences, and the desired product would be obtained with regeneration of the catalyst.…”

Section: Organic Lettersmentioning

confidence: 98%

N-Heterocyclic Carbene-Catalyzed Activation of Esters ofN-Hydroxyphthalimide: A Highly Enantioselective Route to Chiral Dihydropyridinones Bearing an All Carbon Quaternary Stereogenic Center

et al. 2015

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An N-heterocyclic carbene-catalyzed highly enantioselective [3 + 3] annulation reaction of N-hydroxyphthalimide (NHPI) 3,3-disubstituted acrylates and N-Ts ketimines was developed. In most cases, the desired chiral dihydropyridinone products bearing an all carbon quaternary stereogenic center could be obtained in good yields with excellent enantioselectivities (>99% ee's), which demonstrated the NHPI acrylates as a kind of excellent substrate in NHC-catalysis.

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Section: Organic Lettersmentioning

confidence: 98%

N-Heterocyclic Carbene-Catalyzed Activation of Esters ofN-Hydroxyphthalimide: A Highly Enantioselective Route to Chiral Dihydropyridinones Bearing an All Carbon Quaternary Stereogenic Center

et al. 2015

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“…In 2015, Zhong and co-workers demonstrated that NHCs can catalyze the [3+3] annulation reaction of oxindolederived enals 149 and imines 150, leading to the synthesis of optically active spirocyclic oxindoles 151 in the presence of bisquinone oxidant. 42 The products bearing a quaternary spiro-stereocenter were obtained in good to high yield and excellent enantiomeric purity (Scheme 33a). Later, the…”

Section: Short Review Syn Thesismentioning

confidence: 99%

Organocatalyzed [3+3] Annulations for the Construction of Heterocycles

Zhu¹,

Huang

2020

Synthesis

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Six-membered heterocyclic systems are widely distributed in many natural products and pharmaceuticals, and the construction of highly functionalized six-membered heterocyclic compounds is an important topic in modern organic synthesis. Organocatalyzed [3+3] annulations represents an important method for assembling a substantial variety of six-membered cycles that contain one or more heteroatoms. This review describes the development of organocatalyzed [3+3] annulations for the synthesis of six-membered heterocycles, including organocatalysis using secondary amines, tertiary amines, phosphines, chiral phosphoric acids and N-heterocyclic carbenes.1 Introduction2 Secondary Amine Catalyzed [3+3] Annulations2.1 Synthesis of Nitrogen Heterocycles2.2 Synthesis of Oxygen Heterocycles2.3 Synthesis of Sulfur Heterocycles3 Tertiary Amine Catalyzed [3+3] Annulations3.1 Catalysis through Multiple Hydrogen-Bonding Interactions3.2 Catalysis of Tertiary Amines as Lewis Bases4 Phosphine-Catalyzed [3+3] Annulations4.1 Synthesis of Nitrogen Heterocycles4.2 Synthesis of Oxygen Heterocycles4.3 Synthesis of Heterocycles Containing Two or More Heteroatoms5 Chiral Phosphoric Acid Catalyzed [3+3] Annulations5.1 Synthesis of Nitrogen Heterocycles5.2 Synthesis of Heterocycles Containing Two or More Heteroatoms6 N-Heterocyclic Carbene Catalyzed [3+3] Annulations6.1 Synthesis of Nitrogen Heterocycles6.2 Synthesis of Oxygen Heterocycles6.3 Synthesis of Heterocycles Containing Two or More Heteroatoms7 Conclusion and Outlook

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“…We hypothesized that it might be possible to realize such a switchable synthesis of spirocyclopentane oxindoles by choosing isatin‐derived enals and N‐sulfonyl ketimines as substrates. Based on literature precedence, isatin‐derived enals can easily form the three‐carbon homoenolate component, and N‐sulfonyl ketimines have been proven to act as a useful building block for structurally complex molecular synthesis . Inspired by the mentioned challenge, we envisioned a switchable asymmetric access to spirocyclopentane oxindoles either incorporating a β‐lactam or an enaminone moiety bearing multiple stereogenic centers (Scheme ).…”

Section: Figurementioning

confidence: 99%

Switchable Access to Different Spirocyclopentane Oxindoles by N‐Heterocyclic Carbene Catalyzed Reactions of Isatin‐Derived Enals and N‐Sulfonyl Ketimines

et al. 2017

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Anovel NHC-catalyzed annulation protocol for the asymmetric synthesis of biologically important b-lactam fused spirocyclopentane oxindoles with four contiguous stereocenters,i ncluding two quaternary carbon centers,w as developed. Alternatively,s pirocyclopentane oxindoles containing an enaminone moiety can be achieved using the same starting materials,isatin-derived enals,and N-sulfonyl ketimines,inthe presence of as lightly different NHC catalytic system. This switchable annulation strategy enables the selective assembly of both heterocyclic scaffolds with good yields and excellent enantioselectivities for abroad range of substrates.Interesting structurally complex molecules which show aw ide spectrum of biological activity have inspired chemists to design rational and valuable strategies for assembling synthetically challenging structural motifs. [1, 2] Ap articularly privileged structure with regard to both their structural complexity and their biological activity is the polycyclic spirooxindole scaffold. [1e, 2h,l] Representative examples of natural products incorporating the spirocyclopentane oxindole backbone,f or example,c yclopiamines,c itrinadins, marcfortines,n otoamides,a nd paraherquamides,a re shown in Figure 1. [3] To highlight the pharmaceutical relevance of these structures,m arcfortine Ae xhibits potential antiparasitic and anthelmintic activity.T hus its derivatives have been screened as potential clinical candidates for the treatment of gastrointestinal nematodes. [3h,i] Despite the unprecedented progress which has been made in asymmetric synthesis by employing organocatalysis, [2] thec onstruction of strained polycyclic structures with multiple and all-carbon quaternary stereocenters is still ac hallenge.W ithin this context, the development of novel efficient synthetic transformations for the catalytic asymmetric assembly of such structures is highly desirable.Recently,N -heterocyclic carbenes (NHCs) emerged as ap owerful tool for enantioselective CÀCb ond formations. Depending on the electronic and steric properties of the NHC and the substrates,different reactive intermediates beside the classical acyl anion equivalent, for example,a cyl azolium, [4] enolate, [5] and homoenolate [6] equivalents,c an be utilized for the asymmetric synthesis of highly enantioenriched structures.[7] Furthermore,t remendous advances have been made in the field of switchable synthesis through catalytic regiodivergent procedures.A sd ocumented in recent research, [6k, 8] this elegant synthesis strategy always involved careful control of the NHC reaction mode,h omoenolate versus either enolate or acyl anion reactivity,b ased on the different electronic and steric characteristics of the NHC catalyst. However,t he development of switchable synthetic protocols using the same NHC reaction mode,p roceeding through different reaction pathways,r emains af ormidable challenge. We hypothesized that it might be possible to realize such as witchable synthesis of spirocyclopentane oxindoles by choosing isat...

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Rapid Access to Spirocylic Oxindoles: Application of Asymmetric N-Heterocyclic Carbene-Catalyzed [3 + 3] Cycloaddition of Imines to Oxindole-Derived Enals

Cited by 92 publications

References 93 publications

N-Heterocyclic Carbene-Catalyzed Activation of Esters ofN-Hydroxyphthalimide: A Highly Enantioselective Route to Chiral Dihydropyridinones Bearing an All Carbon Quaternary Stereogenic Center

N-Heterocyclic Carbene-Catalyzed Activation of Esters ofN-Hydroxyphthalimide: A Highly Enantioselective Route to Chiral Dihydropyridinones Bearing an All Carbon Quaternary Stereogenic Center

Organocatalyzed [3+3] Annulations for the Construction of Heterocycles

Switchable Access to Different Spirocyclopentane Oxindoles by N‐Heterocyclic Carbene Catalyzed Reactions of Isatin‐Derived Enals and N‐Sulfonyl Ketimines

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