Phosphoric Acid Catalyzed Aldehyde Addition to in Situ Generated <i>o</i>-Quinone Methides: An Enantio- and Diastereoselective Entry toward <i>cis</i>-3,4-Diaryl Dihydrocoumarins

Spanka, Matthias; Schneider, Christoph

doi:10.1021/acs.orglett.8b01865

Cited by 60 publications

(26 citation statements)

References 67 publications

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“…[1] Consequently, several groups have developed catalytic enantioselective syntheses of 3,4-disubstituted chroman-2-ones [2] and, to a much lesser extent, 3,3-disubstituted homologues (Scheme 1). This cyclization sequence was extended to an emerging organocatalytic decarboxylative-chlorination reaction in the presence of trichloroquinolinone and by means of a bifunctional cinchona derived Brønsted base which gave rise to the formation of dihydrocoumarins (up to 79:21 er) with a tertiary chlorinated stereocenter.…”

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confidence: 99%

“…[1] Consequently, several groups have developed catalytic enantioselective syntheses of 3,4-disubstituted chroman-2-ones [2] and, to a much lesser extent, 3,3-disubstituted homologues (Scheme 1). [1] Consequently, several groups have developed catalytic enantioselective syntheses of 3,4-disubstituted chroman-2-ones [2] and, to a much lesser extent, 3,3-disubstituted homologues (Scheme 1).…”

mentioning

confidence: 99%

“…This cyclization sequence was extended to an emerging organocatalytic decarboxylative-chlorination reaction in the presence of trichloroquinolinone and by means of a bifunctional cinchona derived Brønsted base which gave rise to the formation of dihydrocoumarins (up to 79:21 er) with a tertiary chlorinated stereocenter.Amongst the privileged coumarin scaffolds in medicinal chemistry, the dihydrocoumarin derivatives are widely distributed within naturally occurring molecules and bioactive compounds. [1] Consequently, several groups have developed catalytic enantioselective syntheses of 3,4-disubstituted chroman-2-ones [2] and, to a much lesser extent, 3,3-disubstituted homologues (Scheme 1). [3] Nevertheless, the construction of enantioenriched 3-substituted derivatives turned out to be more challenging.…”

mentioning

confidence: 99%

“…Amongst the privileged coumarin scaffolds in medicinal chemistry, the dihydrocoumarin derivatives are widely distributed within naturally occurring molecules and bioactive compounds. [1] Consequently, several groups have developed catalytic enantioselective syntheses of 3,4-disubstituted chroman-2-ones [2] and, to a much lesser extent, 3,3-disubstituted homologues (Scheme 1). [3] Nevertheless, the construction of enantioenriched 3-substituted derivatives turned out to be more challenging.…”

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C5‐Disubstituted Meldrum's Acid Derivatives as Platform for the Organocatalytic Synthesis of C3‐Alkylated Dihydrocoumarins

Martzel

Annibaletto

Levacher³

et al. 2019

Adv Synth Catal

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C5-disubstituted Meldrum's acid precursors were shown to be a useful platform for the synthesis of an array of 3-alkylated dihydrocoumarins with up to 93:7 er, thanks to an enantioselective domino cyclization-decarboxylative-protonation reaction triggered by an unprecedented benzhydrylderived cupreine organocatalyst. This cyclization sequence was extended to an emerging organocatalytic decarboxylative-chlorination reaction in the presence of trichloroquinolinone and by means of a bifunctional cinchona derived Brønsted base which gave rise to the formation of dihydrocoumarins (up to 79:21 er) with a tertiary chlorinated stereocenter.Amongst the privileged coumarin scaffolds in medicinal chemistry, the dihydrocoumarin derivatives are widely distributed within naturally occurring molecules and bioactive compounds. [1] Consequently, several groups have developed catalytic enantioselective syntheses of 3,4-disubstituted chroman-2-ones [2] and, to a much lesser extent, 3,3-disubstituted homologues (Scheme 1). [3] Nevertheless, the construction of enantioenriched 3-substituted derivatives turned out to be more challenging. To the best of our knowledge, the group of Scheidt has reported the single one-step asymmetric construction of 3-substituted dihydrocoumarins upon NHC organocatalysis eliciting a (4 + 2) cycloaddition reaction with er ranging from 75:25 to 93:7. [4] Beside the elegant but two steps enamine-based approaches developed by Xie and Liu, [5a-e] requiring the final oxidation of a lactol intermediate, List and co-workers have pioneered the challenging enantiose-lective delivery of a small proton atom to ketene dithioacetals. [5f] One of the obtained product was hydrolyzed into an a-phenyl dihydrocoumarin with high enantiomeric excess. In view of this background, an expedious synthetic sequence furnishing C3-substituted dihydrocoumarin remains desirable.Very recently, the group of Guiry achieved the synthesis of a series of 3-aryl dihydrocoumarins with er ranging from 65:35 to 94:6 (Scheme 1b). [6] This functionalization strategy takes advantage of the palladium-catalyzed decarboxylative protonation reaction [7] in the presence of ephedrine as a chiral stoichiometric source of proton. Although several teams ventured into this convenient enantioselective protonation (EP) strategy, mostly from hemimalonic esters in organocatalysis, only the groups of Brunner, Rouden, Zhang and Song succeeded in getting good er (rarely > 95:5) albeit at the expense of the use of high catalyst loading (up to 1 equiv.). [8,9] Scheme 1.

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“…[1] Consequently, several groups have developed catalytic enantioselective syntheses of 3,4-disubstituted chroman-2-ones [2] and, to a much lesser extent, 3,3-disubstituted homologues (Scheme 1). [1] Consequently, several groups have developed catalytic enantioselective syntheses of 3,4-disubstituted chroman-2-ones [2] and, to a much lesser extent, 3,3-disubstituted homologues (Scheme 1).…”

mentioning

confidence: 99%

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confidence: 99%

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C5‐Disubstituted Meldrum's Acid Derivatives as Platform for the Organocatalytic Synthesis of C3‐Alkylated Dihydrocoumarins

Martzel

Annibaletto

Levacher³

et al. 2019

Adv Synth Catal

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“…Then they reacted with β-dicarbonyl compounds. The same research group prepared cis-3,4-diarylchromanols through reaction of o-hydroxybenzhydryl alcohols and aryl acetaldehydes (Scheme 24) [39]. Ortho substitution in the aryl group of o-hydroxybenzhydryl alcohol enhanced the enantioselectivity.…”

Section: Cycloaddition Of Ortho-quinone Methidesmentioning

confidence: 99%

Recent Advances in Organocatalyzed Asymmetric Synthesis of Benzopyran and Benzodihydropyran (Chromane) Nuclei

Dalpozzo

Mancuso

2019

Symmetry

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Benzopyran and benzodihydropyran (chromane) nuclei are the core structure of many natural products, in particular flavonoids. Many compounds possessing this structure are nutraceuticals, pharmaceutical nutrients. Therefore, benzopyran and chromane scaffolds are important building blocks in organic synthesis and many efforts have been made to set up efficient methods for their synthesis. In particular, asymmetric methods are of great importance, being natural products, and generally chiral substances. This review aims to cover literature in the range 2017-first half of 2019.It should be noted that the oxa-Michael-Henry reaction between two molecules of nitrostyrene was not observed. Symmetry 2020, 12, x FOR PEER REVIEW 4 of 33 Scheme 2. Heterogeneous enantioselective synthesis of chromanes.Xia, Xu and co-workers performed an enantioselective, organocatalytic oxa-Michael-nitro-Michael reaction, but in this case, too, 2-hydroxynitrostyrenes reacted only with β-nitroolefins different from themselves [10]. The reaction afforded chiral chromane derivatives bearing three contiguous stereogenic centers (Scheme 3). The all-S stereochemistry was assigned by X-ray analysis. Subsequently, Andrés, Pedrosa and co-workers extended the reaction to polymer-supported squaramides [11]. Initially, they tested some 4-vinylphenyl-substituted squaramides and found that Squa2 (see Scheme 1, 5 mol%, rt, 12-72 h in dichloromethane) gave the best results (65-88% yields, 63:27 to >99:1 dr, 70-> 99% ee, 13 examples). The absolute configuration was once more (2S,3S,4S) and was established by X-ray analysis. The configuration of the minor isomer was instead established as (2S,3R,4S) by comparison of the 1 H-NMR coupling constants of the two diastereomers. Then Squa2 was co-polymerized with styrene and divinylbenzene and the experiments were repeated (65-86% yields, 58:42 to >99:1 dr, 56-74% ee). The polymer-supported catalyst was also recovered and recycled five times without affecting yields and selectivity. Finally, the enantiomers were obtained from a squaramide derived from (1R,2R)-1,2-cyclohexanediamine instead of Squa2 derived from α-amino acid. The authors attributed the opposite stereochemistry to a different assembly of the ternary complex formed by catalyst, nitroalkene and 2-hydroxynitrostyrene in the two cases. S O HN HO HO OHC Symmetry 2019, 11, 1510 5 of 31 Symmetry 2020, 12, x FOR PEER REVIEW 5 of 33 Scheme 3. Organocatalytic oxa-Michael nitro-Michael domino reaction.Another domino Michael/hemiacetalization (see also Scheme 2, eq 3) was carried out between aliphatic aldehydes and (E)-2-(2-nitrovinyl)phenols under modularly designed organocatalysts (Scheme 4) [12]. Cis-3,4-disubstituted chroman-2-ones were obtained after oxidation of the hemiacetal intermediate or chromanes after dehydroxylation. The reaction was scaled up to 0.5 mmol scale, without significant modification of yield and selectivity. The absolute stereochemistry was determined by the optical rotation of known compounds. Scheme 4. Domino reaction catalyzed by MDO o...

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New Developments in Enantioselective Brønsted Acid Catalysis with Strong Hydrogen Bond Donors

Dorsch

Schneider

2022

Asymmetric Organocatalysis

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Phosphoric Acid Catalyzed Aldehyde Addition to in Situ Generated o-Quinone Methides: An Enantio- and Diastereoselective Entry toward cis-3,4-Diaryl Dihydrocoumarins

Cited by 60 publications

References 67 publications

C5‐Disubstituted Meldrum's Acid Derivatives as Platform for the Organocatalytic Synthesis of C3‐Alkylated Dihydrocoumarins

C5‐Disubstituted Meldrum's Acid Derivatives as Platform for the Organocatalytic Synthesis of C3‐Alkylated Dihydrocoumarins

Recent Advances in Organocatalyzed Asymmetric Synthesis of Benzopyran and Benzodihydropyran (Chromane) Nuclei

New Developments in Enantioselective Brønsted Acid Catalysis with Strong Hydrogen Bond Donors

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