Enantioselective synthesis of 3-fluoro-3-allyl-oxindoles via phosphine-catalyzed asymmetric γ-addition of 3-fluoro-oxindoles to 2,3-butadienoates

Wang, Tianli; Hoon, Ding Long; Lü, Yixin

doi:10.1039/c5cc03289j

Cited by 94 publications

(22 citation statements)

References 76 publications

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“…Based on the obtained results and our previous studies,– the plausible stereocontrol models are presented in Table . We propose that the amide and carbamate portions of the catalyst interact with cyclic imines through hydrogen‐bonding interactions, which contribute significantly to the key transition‐state models leading to the formation of the observed major stereoisomer.…”

Section: Methodsmentioning

confidence: 81%

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: 81%

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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“…In 2014, the Lu group developed 2,3-butadienoates as Michael acceptors for the asymmetric addition reaction with 3-fluorooxindoles 233 for the synthesis of 3-fluoro-3-allyloxindoles containing a C–F quaternary center (Scheme 133). 336 The l- threonine derived phosphine-amide C78 was demonstrated as the best choice of catalyst, which was able to catalyze the conversion of several 2,3-butadienoates 316 into the corresponding products with excellent yields (88−95%) and high enantioselectivities (83−94% ee). The ester group of 2,3-butadienoates almost have no effect on the reaction efficiency, and the groups including methyl, t -butyl, benzyl, and bulky anthryl were all well tolerated in the reaction, affording the same level of yields and enantioselectivities.…”

Section: Modern Methods For Construction Of Quaternary C–f Stereogenimentioning

confidence: 99%

Modern Approaches for Asymmetric Construction of Carbon–Fluorine Quaternary Stereogenic Centers: Synthetic Challenges and Pharmaceutical Needs

et al. 2018

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New methods for preparation of tailor-made fluorine-containing compounds are in extremely high demand in nearly every sector of chemical industry. The asymmetric construction of quaternary C−F stereogenic centers is the most synthetically challenging and, consequently, the least developed area of research. As a reflection of this apparent methodological deficit, pharmaceutical drugs featuring C−F stereogenic centers constitute less than 1% of all fluorine-containing medicines currently on the market or in clinical development. Here we provide a comprehensive review of current research activity in this area, including such general directions as asymmetric electrophilic fluorination via organocatalytic and transition-metal catalyzed reactions, asymmetric elaboration of fluorine-containing substrates via alkylations, Mannich, Michael, and aldol additions, cross-coupling reactions, and biocatalytic approaches. CONTENTS

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“…36 With the use of 3-fluorooxindoles as pronucleophiles, we subsequently realized an enantioselective γ-addition to 2,3-butadienoates for the facile synthesis of optically enriched 3-fluoro-3-allyloxindole derivatives. 37 More recently, we utilized 5H-thiazol-4-ones and 5H-oxazol-4-ones as reaction partners and achieved their enantioselective γ-additions of to 2,3-butadienoates. 38 In the presence of amino acid-derived bifunctional phosphine P-2 or P-10, chiral thiazolones and oxazolones with a heteroatom (S or O)-containing tertiary chiral center were obtained in high yields with excellent enantioselectivities (Scheme 25).…”

Section: Asymmetric γ-Umpolung Additionmentioning

confidence: 99%

Amino Acid-Derived Bifunctional Phosphines for Enantioselective Transformations

et al. 2016

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Even though seminal reports on phosphine catalysis appeared in the 1960s, in the last few decades of the past century trivalent phosphines were viewed primarily as useful ligands for transition-metal-mediated processes. The 1990s saw revived interest in using phosphines in organic catalysis, but the key advances in asymmetric phosphine catalysis have all come within the past decade. The uniqueness of phosphine catalysis can be attributed to the high nucleophilicity of the phosphorus atom. In typical phosphine-catalyzed reactions, nucleophilic attacks of the phosphorus atom on electron-deficient multiple bonds create different reactive ylide-type intermediates. When such structurally diverse zwitterionic species react with a variety of suitable substrates, new reaction patterns are often discovered and a diverse array of reactions can be developed. In recent years, substantial progress has been made in the field of asymmetric phosphine catalysis; many new reactions have been discovered, and numerous enantioselective processes have been reported. However, we felt that powerful and versatile phosphine catalysts that can work for a wide range of asymmetric reactions are still lacking. We therefore set our goal to develop a family of easily derived phosphine catalysts that are efficient in asymmetric induction for a broad range of phosphine-mediated transformations. This Account describes our efforts in the past few years on the development of amino acid-based bifunctional phosphines and their applications to enantioselective processes. Building upon our previous success in primary-amine-mediated enamine catalysis, we first established that bifunctional phosphines could be readily prepared from amino acids. In most of our studies, we chose threonine as the key backbone for catalyst development, and threonine-based monoamino acid or dipeptide bifunctional phosphines have displayed remarkable stereochemical control. We began our investigations by demonstrating the usefulness of our phosphine catalysts in aza-Morita-Baylis-Hillman (aza-MBH) and MBH reactions. We then showed the great power of amino acid/dipeptide phosphines in a wide range of [3 + 2] annulation processes, including [3 + 2] cycloaddition of allenoates to acrylates/acrylamides, [3 + 2] annulation of imines with allenoates, and [3 + 2] cyclization employing MBH carbonates and activated alkenes. By utilizing α-substituted allenoates and activated alkenes, we developed an enantioselective [4 + 2] annulation to access functionalized cyclohexenes. We also devised a novel enantioselective [4 + 2] annulation process by using α-substituted allenones for the construction of 3,4-dihydropyrans. With the use of β'-acetate allenoate, a [4 + 1] annulation process has been designed to access chiral spiropyrazolones. Another array of reactions that make use of the basicity of zwitterionic phosphonium enolate intermediates have been successfully attained, including the first phosphine-catalyzed asymmetric Michael addition, enantioselective allylic substitution of MBH carbo...

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Enantioselective synthesis of 3-fluoro-3-allyl-oxindoles via phosphine-catalyzed asymmetric γ-addition of 3-fluoro-oxindoles to 2,3-butadienoates

Cited by 94 publications

References 76 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

Modern Approaches for Asymmetric Construction of Carbon–Fluorine Quaternary Stereogenic Centers: Synthetic Challenges and Pharmaceutical Needs

Amino Acid-Derived Bifunctional Phosphines for Enantioselective Transformations

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