Asymmetric Alcoholysis of Cyclic Anhydrides

Chen, Yonggang; McDaid, Paul; Deng, Li

doi:10.1021/cr020037x

Cited by 213 publications

(62 citation statements)

References 82 publications

(80 reference statements)

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“…Subsequent intramolecular cyclization reactions of intermediates I afforded precursor 1,2-dihydropyrroles II, which may be converted into dihydropyrrole 3 after protonation. [6] Cinchona alkaloids and their derivatives have been revealed as efficient organocatalysts for many asymmetric reactions, [8] particularly for a variety of asymmetric Cnucleophilic addition reactions in which the basic functionalities of the alkaloid activates acidic a-carbon pronucleophiles (Figure 1). [9][10][11][12] Surprisingly, to the best of our knowledge, isocyanoesters have not yet been used as nucleophiles in these reactions, or in other organic base-catalyzed nucleophilic addition reactions.…”

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confidence: 99%

Organocatalytic Asymmetric Formal [3+2] Cycloaddition Reaction of Isocyanoesters to Nitroolefins Leading to Highly Optically Active Dihydropyrroles

Guo¹,

Xue²,

Zhu³

et al. 2008

Angew Chem Int Ed

183

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Heterocyclic compounds containing a chiral pyrrolidine motif commonly appear in natural alkaloids and pharmaceutically active substances, and serve as building blocks commonly used for total syntheses; therefore there has been great demand for highly efficient asymmetric synthetic methods to access these compounds. [1,2] Optically active 2,3-dihydropyrroles are important unsaturated heterocyclic compounds that can not only be transformed into multisubstituted pyrrolidines for the synthesis of chiral building blocks, but can also be applied to the total synthesis of natural products.[3] The synthetic approaches to access enantioenriched pyrrolidines include chiral-auxiliary-assisted asymmetric synthesis and a number of transition-metal-catalyzed asymmetric dipolar addition reactions.[2] However, organocatalytic approaches to access chiral pyrrolidines are scarce [4] despite the growth in asymmetric organocatalysis in modern organic synthesis. [5] Moreover, the asymmetric catalytic synthesis of chiral 2,3-dihydropyrroles remains elusive and the discovery of catalytic asymmetric reactions that yield optically active 2,3-dihydropyrroles is an important challenge. Over 30 years ago, cycloaddition reactions of metalated isocyanides to a,b-unsaturated carbonyl and nitrile compounds were reported to generate racemic 2,3-dihydropyrroles.[6] An enantioselective version of this transformation may provide a method for direct access to chiral dihydropyrroles and would therefore be valuable in the synthesis of chiral building blocks and related alkaloids.[2] In contrast to the long history of nonasymmetric variants, [6] enantioselective, catalytic cycloaddition reactions of isocyanoesters with electron-deficient olefins are not yet available. Herein, we report the first catalytic asymmetric cycloaddition reaction of isocyanoesters [7] to nitroolefins by using alkaloid-derived bases to form highly functionalized 2,3-dihydropyrroles with excellent enantioselectivities (up to > 99 % ee).Our mechanistic proposal for the formal cycloaddition reaction catalyzed by a chiral base is shown in Scheme 1. The chiral base could promote an asymmetric Michael addition of isocyanoesters 1 to electron-deficient olefins, such as nitroolefins 2, by activating the acidic a-carbon atom of 1 to generate intermediates I. Subsequent intramolecular cyclization reactions of intermediates I afforded precursor 1,2-dihydropyrroles II, which may be converted into dihydropyrrole 3 after protonation. [6] Cinchona alkaloids and their derivatives have been revealed as efficient organocatalysts for many asymmetric reactions, [8] particularly for a variety of asymmetric Cnucleophilic addition reactions in which the basic functionalities of the alkaloid activates acidic a-carbon pronucleophiles (Figure 1). [9][10][11][12] Surprisingly, to the best of our knowledge, isocyanoesters have not yet been used as nucleophiles in these reactions, or in other organic base-catalyzed nucleophilic addition reactions. Despite this, we still believed that cinchona alkaloids...

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Organocatalytic Asymmetric Formal [3+2] Cycloaddition Reaction of Isocyanoesters to Nitroolefins Leading to Highly Optically Active Dihydropyrroles

Guo¹,

Xue²,

Zhu³

et al. 2008

Angew Chem Int Ed

183

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“…[10] Attempts to desymmetrize the eight-membered cyclic anhydride 10 were equally unsuccessful. In the presence of various organocatalysts, including Cinchona-alkaloid derivatives [11] and BINOL-derived chiral phosphoric acids, [12,13] reaction of 10 with methanol at À20 8C was very slow, thus affording, after 48 h, the racemic monoacid 2 a (R = Et) in less than 20 % yield. These results are in sharp contrast to the facile desymmetrization of five-and six-membered meso or prochiral anhydrides such as 11 (Figure 2), thus indicating the challenges associated with the desymmetrization of 1.…”

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Phosphoric Acid Catalyzed Desymmetrization of Bicyclic Bislactones Bearing an All‐Carbon Stereogenic Center: Total Syntheses of (−)‐Rhazinilam and (−)‐Leucomidine B

2014

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In the presence of a catalytic amount of an imidodiphosphoric acid, enantioselective desymmetrization of bicyclic bislactones by reaction with alcohols took place smoothly to afford enantiomerically enriched monoacids having an all-carbon stereogenic center. Concise catalytic enantioselective syntheses of both (À)-rhazinilam and (À)-leucomidine B were subsequently developed using (S)-methyl 4-ethyl-4-formylpimelate monoacid as a common starting material.

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“…[11] As a model substrate, the activated a,b-unsaturated ketone 1 a first underwent an intramolecular oxa-Michael addition in the presence of a cinchona alkaloid followed by electrophilic fluorination with Na 2 CO 3 [12] and N-fluorobenzenesulfonimide (NFSI) to deliver the desired product 3 a. Table 1 summarizes the results of the catalyst evaluation.…”

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confidence: 99%

“…As a compromise of both yield and enantioselectivity, a catalyst loading of 15 mol % was selected for the ensuing study. Lowering the reaction temperature to 0 8C brought no improvement in enantioselectivity, but led to a decrease in the yield and a prolonged reaction time ( [8][9][10][11]. Although higher ee values were obtained in Et 2 O or methyl tert-butyl ether (MTBE), the yields were markedly diminished probably due to the poor solubility of NFSI in these two solvents (Table 2, entries 12 and 15).…”

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confidence: 99%

“…[13] To propose a mechanism for the reaction, we assumed that the oxa-Michael addition was the enantiodiscriminating step and the stereocenter thus formed would govern the stereoselectivity of the electrophilic fluorination process as we have previously demonstrated. [10] Based on the experimental results and previous studies, [11] we proposed a transitionstate model to explain the stereochemical outcome of the reaction (Scheme 3). The bifunctional catalyst may activate both the nucleophile and the electrophilic acceptor through a hydrogen-bonding interaction, directing the oxygen nucleophile to attack the Re face of the double bond to form the Rconfigured product.…”

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Asymmetric Synthesis of Fluorinated Flavanone Derivatives by an Organocatalytic Tandem Intramolecular Oxa‐Michael Addition/Electrophilic Fluorination Reaction by Using Bifunctional Cinchona Alkaloids

Wang

Cui

Chai

et al. 2009

Chemistry A European J

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Flavanones are a large family of natural products with many important biological activities, such as antitumor and anti-inflammatory properties. [1, 2] However, despite intensive research devoted to the synthesis of flavanone derivatives, [3] only a limited number of methods, particularly catalytic asymmetric methods, are available for the asymmetric synthesis of this class of compound.[4] Structurally, the asymmetric, intramolecular oxa-Michael addition reaction of a phenol to chalcone would provide an easy access to chiral flavanones due to the ready availability of the starting materials. However, it was not until 2007 that a breakthrough based on this strategy, by using an organocatalytic method, was accomplished, by Scheidt and co-workers, [4d] probably due to the low reactivity of the substrates. They addressed this challenge by utilizing an activated, unsaturated ketone, 1, as the substrate and bifunctional chiral thioureas as catalysts (Scheme 1). Recently, Feng and co-workers [4g] reported a metal-catalyzed version of the same reaction employing chiral N,N'-dioxide nickel(II) complexes with excellent results. In view of these results, there is still the potential for the development of new organocatalysts to effect an asymmetric intramolecular oxa-Michael addition as a route to synthesize chiral flavanones.On the other hand, the introduction of a fluorine atom into a compound often results in important changes in its biological activity, which can lead to potential applications in medicinal chemistry and the pharmaceutical industry. [5] One of the most challenging subjects in the field of synthetic fluorine chemistry is the enantioselective construction of the C À F bond at a stereogenic carbon center.[6] Since the first asymmetric fluorination reagents were reported by Differding and Lang [7a] in 1988 and the first catalytic enantioselective fluorination was disclosed by Hintermann and Togni [7b] in 2000, this intriguing field of catalytic asymmetric fluorination has been blooming. [8,9] Our group has developed a onepot tandem reaction for the synthesis of fluorinated flavanones, from b-ketoesters and aldehydes, with excellent diastereoselectivities.[10] On the basis of these results, we envisaged that by using an appropriate bifunctional catalyst, an organocatalytic, asymmetric, intramolecular oxa-Michael addition of 1 would produce enantioenriched 2, which could then be subjected to electrophilic fluorination to provide novel, chiral, fluorinated flavanone derivatives (Scheme 1). Herein, we report the details of this research.Cinchona alkaloids and their derivatives were selected as catalysts to be investigated due to their easy availability and well-documented power as bifunctional organocatalysts in

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Asymmetric Alcoholysis of Cyclic Anhydrides

Cited by 213 publications

References 82 publications

Organocatalytic Asymmetric Formal [3+2] Cycloaddition Reaction of Isocyanoesters to Nitroolefins Leading to Highly Optically Active Dihydropyrroles

Organocatalytic Asymmetric Formal [3+2] Cycloaddition Reaction of Isocyanoesters to Nitroolefins Leading to Highly Optically Active Dihydropyrroles

Phosphoric Acid Catalyzed Desymmetrization of Bicyclic Bislactones Bearing an All‐Carbon Stereogenic Center: Total Syntheses of (−)‐Rhazinilam and (−)‐Leucomidine B

Asymmetric Synthesis of Fluorinated Flavanone Derivatives by an Organocatalytic Tandem Intramolecular Oxa‐Michael Addition/Electrophilic Fluorination Reaction by Using Bifunctional Cinchona Alkaloids

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