An Organocatalytic Asymmetric Friedel–Crafts Addition/Fluorination Sequence: Construction of Oxindole–Pyrazolone Conjugates Bearing Vicinal Tetrasubstituted Stereocenters

Bao, Xiaoze; Wang, Baomin; Cui, Longchen; Zhu, Guodong; He, Yuli; Qü, Jingping; Song, Yuming

doi:10.1021/acs.orglett.5b02470

Cited by 115 publications

(35 citation statements)

References 67 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…PCN-Q1-1 provided the product with ee values greater than 99 %a nd high diastereoselectivities over 20:1 dr.T he fact that the enantioselective performances are comparable strongly indicates that the Q1 molecules graftedo nP CN through the DVB molecular linker,w hich increases the space distance, inherit the mobility and original chiral environment of the homogeneous analogue (Q1). In addition, as demonstrated in our previous work, [18] the enantioselectivity stemmed from Q1 in the first step and is independento ft he fluorination in the second step. In addition, as demonstrated in our previous work, [18] the enantioselectivity stemmed from Q1 in the first step and is independento ft he fluorination in the second step.…”

supporting

confidence: 73%

“…ChemCatChem 2018ChemCatChem , 10,1248ChemCatChem -1252 www.chemcatchem.org 2018 Wiley-VCH Verlag GmbH &Co. KGaA, Weinheim cently reported. [18] The oxindole-pyrazolone conjugates have 3-substitued-3-aminooxindoles motifs, which constitutet he core structure of numerousn atural products and drug candidates. [19] In this study,w ef irst evaluated the performance of the prepared heterogeneous catalysts (PCN-Q1-1 and PCN-Q1-2) in the enantioselective addition of pyrazolone 2a to isatin ketimine 1a.T oo ur delight, both PCN-Q1-1 and PCN-Q1-2 were highly active, and they both catalyzed the reactiont o afford product 3 in high yields with high ee values (Table 1, entries 2a nd 3).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Porous Carbon Nanosheet‐Supported Chiral Squaramide for Highly Enantioselective Friedel–Crafts Reaction

Zhao

Bao

et al. 2018

ChemCatChem

Self Cite

View full text Add to dashboard Cite

Porous carbon nanosheets (PCNs) wereu sed for the first time as as upport to immobilize aq uinine-squaramide catalyst for the asymmetric Friedel-Craftsa ddition of pyrazolonest oi satin ketimines. Relying on its open structure with am acroporous network as well as hydrophobicity,t he PCN-supported catalyst presented catalytic performance comparable to its homogeneous catalyst;t he products were obtained in high yields (up to 90 %) with high ee values (up to 99 %). Recycling batch reactions together with ac ontinuous flow process confirmedt he stabilityo ft he catalyst.The heterogenization of homogeneous chiral catalysts is considered an effective approach towards sustainable asymmetric synthesis. [1] This strategy can providee asily recyclable solid catalysts with clearly known actives ites similar to their homogeneous counterparts. Nevertheless,h eterogenized chiral catalysts achievedb yt he surfacec ovalentt ethering strategy usually exhibit poor enantioselectivity owing to limited free space for chiral induction [2] and uncontrolled activity owing to certain side reactions initiated by the supports. Hence, the structural features and physicochemical properties of catalyst support materials are criticalt od etermine the performance of heterogenizedc atalysts.

show abstract

supporting

confidence: 73%

mentioning

confidence: 99%

Porous Carbon Nanosheet‐Supported Chiral Squaramide for Highly Enantioselective Friedel–Crafts Reaction

Zhao

Bao

et al. 2018

ChemCatChem

Self Cite

View full text Add to dashboard Cite

show abstract

“…A highly and useful one‐pot consecutive method, comprising of an organocatalytic AF‐C‐type addition reaction of 4‐nonsubstiuted pyrazolone derivatives to isatin obtained N ‐Boc ketimine derivatives and a subsequent diastereoselective fluorination of the pyrazolone scaffold, was achieved. This reaction sequence provides oxindole‐pyrazolone products presenting vicinal tetrafunctionalized stereocenters with a 0.5 mol % catalyst loading in excellent yield with high enantio‐ and diastereocontrol . N ‐substitution of the oxindole nitrogen has been explored ( 190 a – d ).…”

Section: Organocatalyzed Asymmetric Friedel‐crafts Reactions Usingmentioning

confidence: 99%

Organocatalyzed Asymmetric Friedel‐Crafts Reactions: An Update

Heravi

Zadsirjan

Heydari

et al. 2019

The Chemical Record

View full text Add to dashboard Cite

The Friedel‐Crafts alkylation (F‐CA) reaction is a special kind of carbon−carbon bond formations, which is frequently being used for the formation of such bond in some aromatic rings in organic synthesis. Its asymmetric variant gives enantiorich products. Commonly, an in situ organocatalyzed asymmetric Friedel‐Crafts alkylation (AF‐CA) proceeds via generation of an enamine as an intermediate. The organocatalyzed‐AF‐CA was discovered and established in the mid‐1980s and reviewed comprehensively in 2010. In this report, we are trying to update the applications of novel organocatalysts in the AF‐CA as a versatile synthetic strategy, which is frequently used in the effective asymmetric synthesis of complex molecules, pharmaceutically important compounds and most importantly in the total synthesis of biologically active natural products.

show abstract

“…[13] Fort he efficient creation of 3,2'-pyrrolidinyl spirooxindoles,w hich contain at etrasubstituted stereogenic center at the 3-position, we reasoned that ap hosphine-catalyzed cycloaddition reaction employing isatin-derived ketimines would be an ideal strategy (Scheme 3). However,t he reactivity of the ketimine starting materials poses serious challenges.D espite the widespread use of isatin-derived ketimines in other reactions,f or example,Mannich reactions, [14] Strecker reactions, [15] (aza) FriedelCrafts additions, [16] aza-Morita-Baylis-Hillman reactions, [17] and aza-Henry reactions, [18] they have never been used in phosphine-catalyzed annulation reactions.W eh ypothesized that our amino acid based phosphine catalysts may provide sufficient activation for the challenging ketimine substrates, since such phosphines are very nucleophilic and are not hindered owing to the direct linkage of the phosphorus atom to ap rimary carbon. To make our method amenable for the synthesis of multisubstituted 3,2'-pyrrolidinyl spirooxindoles, we envisaged that g-substituted allenes [19] could be used as reaction partners.H erein, we disclose the first phosphinecatalyzed [3+ +2] annulation with isatin-derived ketimines and simple/g-substituted allenoates to form 3,2'-pyrrolidinyl spirooxindoles in ahighly enantioselective manner.…”

mentioning

confidence: 99%

Phosphine‐mediated Highly Enantioselective Spirocyclization with Ketimines as Substrates

et al. 2016

View full text Add to dashboard Cite

Phosphine-catalyzed enantioselective annulation reactions involving ketimines are ad aunting synthetic challenge owingt ot he intrinsic low reactivity of ketimine substrates.Ah ighly enantioselective [3+ +2] cycloaddition reaction that makes use of isatin-derived ketimines as reaction partners was developed. Notably,b oth simple and g-substituted allenoates could be utilized,and various 3,2'-pyrrolidinyl spirooxindoles with at etrasubstituted stereocenter were obtained in excellent yields and with nearly perfect enantioselectivity (> 98 %eei nall cases).The ubiquity of spirocyclicf rameworks in natural products has long been af actor in galvanizing organic chemists to explore their preparation through the construction of carbocyclic and heterocyclic precursors.A mong established strategies,p hosphine-triggered annulation reactions have proven to be an efficient and versatile approach ever since the pioneering discovery of phosphine-catalyzed [3+ +2] cyclization by Lu and co-workers.[1] Nitrogen-containing ring systems are prevalent molecular architectures that are widely found in natural products and are extremely valuable as synthetic intermediates.Phosphine-catalyzed allene-imine annulation [2] is one of the most powerful methods for constructing such motifs,a nd has been widely employed in numerous syntheses of natural products and bioactive molecules. [3] In the vast majority of reported examples,aldehydederived aldimines are the electrophilic reaction partners utilized in these reactions.K etimines,o nt he other hand, are seldom used. Theu npopularity of ketimines in phosphine catalysis is likely due to their intrinsic low reactivity,s teric bulkiness,a nd the associated difficulty with stereochemical control. There are only two reports to date in which ketimines are employed for phosphine catalysis in anon-stereoselective manner, [4] and only one enantioselective example by Sasai and co-workers,which describes the use of cyclic ketimines in [4+ +2] annulation with allenoates.[5] Notably,t he cyclic ketimines utilized by Sasai et al. were rather special and the reaction suffered from arelatively narrow substrate scope.As part of our continued interests in phosphine catalysis, [6] we became interested in developing an efficient strategy for the use of ketimine substrates in common phosphine-mediated annulation reactions for the construction of molecular structures of biological significance (Scheme 1).Spirooxindoles are prominent structural motifs that are often found in natural products.A mong different spirooxindole cores,t he pyrrolidinyl spirooxindole frameworks represent av ery important class owing to their excellent bioactivity profiles.Most of the current research efforts have been focused on the synthesis of 3,3'-pyrrolidinyl spirooxindoles, [7] however, 3,2'-pyrrolidinyl spirooxindoles are also undeniably important and display ab road spectrum of biological activities [8] (Scheme 2). There are only ah andful of reports describing the synthesis of 3,2'-pyrrolidinyl scaffolds, [9] and these...

show abstract

An Organocatalytic Asymmetric Friedel–Crafts Addition/Fluorination Sequence: Construction of Oxindole–Pyrazolone Conjugates Bearing Vicinal Tetrasubstituted Stereocenters

Cited by 115 publications

References 67 publications

Porous Carbon Nanosheet‐Supported Chiral Squaramide for Highly Enantioselective Friedel–Crafts Reaction

Porous Carbon Nanosheet‐Supported Chiral Squaramide for Highly Enantioselective Friedel–Crafts Reaction

Organocatalyzed Asymmetric Friedel‐Crafts Reactions: An Update

Phosphine‐mediated Highly Enantioselective Spirocyclization with Ketimines as Substrates

Contact Info

Product

Resources

About