Catalytic asymmetric synthesis of CF<sub>3</sub>-substituted tertiary propargylic alcohols via direct aldol reaction of α-N<sub>3</sub>amide

Noda, Hidetoshi; Amemiya, Fuyuki; Weidner, Karin; Kumagai, Naoya; Shibasaki, Masakatsu

doi:10.1039/c7sc00330g

Cited by 64 publications

(24 citation statements)

References 115 publications

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“…Catalytic asymmetric aldol reaction is recognized as one of the most efficient strategies for driving it to form the desired enantioenriched β‐hydroxy carbonyl moiety with the concomitant formation of a carbon‐carbon bond, and therefore, as a fundamental transformation in organic chemistry, has attracted broad interest over the past two decades . Since List et al .…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Extended Bipyridine‐proline Chiral Catalysts and Resulting Effects on the Asymmetric Aldol Reactions of Bulkier Aldehyde Derivatives with Cyclohexanone

Sun

Bai

et al. 2020

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Axially‐unfixed 2,2′‐bipyridine‐based chiral catalysts were synthesized using enantiopure amino acids as chiral sources, which were successfully used in asymmetric aldol reactions of p‐nitrobenzaldehyde with cyclohexanone, while the bulkier aldehyde derivatives (2‐naphthaldehyde, 9‐anthracenecarboxaldehyde, and 1‐pyrenecarboxaldehyde) were selected to further elucidate the catalytic properties. Particularly, the influences of the bipyridine‐proline chiral structures and the polarities of used solvents (petroleum ether, toluene, CH2Cl2, ethanol, DMF, DMSO, and water) on the catalytic performance were investigated. The results indicated that the structure of bipyridine catalysts, the molecular volume of aldehydes, and the polarity of solvents have significant eﬀects on the catalytic activities, in which, the smaller steric effects were conducive to the improvement of the yields and stereoselectivities for asymmetric aldol reaction, along with the increased polarity of used solvents and the decreased molecular volume of aldehydes. Meanwhile, the chemical identity of all compounds was confirmed by 1H‐NMR, 13C‐NMR, HRMS, and HPLC analysis.

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Section: Introductionmentioning

confidence: 99%

Synthesis of Extended Bipyridine‐proline Chiral Catalysts and Resulting Effects on the Asymmetric Aldol Reactions of Bulkier Aldehyde Derivatives with Cyclohexanone

Sun

Bai

et al. 2020

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“…Whereas amides and carboxylic acids, which are regarded as more challenging aldol donor substrates in terms of reluctant enolization, have been incorporated in the direct aldol reaction manifold, no enantioselective variants have been reported (Scheme b) . Herein, we report an enantio‐ and diastereoselective direct catalytic aldol reaction of α‐fluorinated ketones 2 and α‐hydroxylated 7‐azaindoline amides 1 (Scheme c) . The reaction was developed in a diastereodivergent fashion, affording both syn ‐ and anti ‐configured 1,2‐dihydroxycarboxylic acid units with fluorinated substituents.…”

Section: Methodsmentioning

confidence: 99%

Direct Catalytic Asymmetric Aldol Reaction of α‐Alkoxyamides to α‐Fluorinated Ketones

2019

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α‐Oxygen‐functionalized amides found particular utility as enolate surrogates for direct aldol couplings with α‐fluorinated ketones in a catalytic manner. Because of the likely involvement of open transition states, both syn‐ and anti‐aldol adducts can be accessed with high enantioselectivity by judicious choice of the chiral ligands. A broad variety of alkoxy substituents on the amides and aryl and fluoroalkyl groups on the ketone were tolerated, and the corresponding substrates delivered a range of enantioenriched fluorinated 1,2‐dihydroxycarboxylic acid derivatives with divergent diastereoselectivity depending on the ligand used. The amide moiety of the aldol adduct was transformed into a variety of functional groups without protection of the tertiary alcohol, showcasing the synthetic utility of the present asymmetric aldol process.

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“…[54] In 2017, Shibasaki and co-workers reportedadirect catalytic asymmetrica ldol reactiono fa na mide with CF 3 ketones (Scheme 29). [55] Their designed amide underwent facile enolization and subsequent enantioselective aldol addition [56] in the presenceo facopper(II) triflate, bis(hydroxamic acid) 52, [57] and Barton'sb ase. Thisc atalytic system was optimized specifically for alkynyl CF 3 ketones, and aw ide range of productswere obtained with high syn-a nd enantioselectivities.…”

Section: Aldol Reactionsmentioning

confidence: 99%

Catalytic Asymmetric Synthesis of α‐Trifluoromethylated Carbinols: A Case Study of Tertiary Propargylic Alcohols

2018

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Enantioenriched CF 3 -substituted tertiary alcohols have been applied in ab road range of chemical disciplines, including medicinal chemistry and agrochemistry. The widely prescribed anti-HIV pharmaceutical efavirenz is one particular example of the application of these chiral building blocks. Because the typical synthetic route to this small drug molecule involves the stoichiometric use of ac hiral promoter,s ignificant effort has been devoted to the development of catalytic alternatives for accessing this building block.I n this Focus Review,w es ummarize the catalytic asymmetric synthesis of CF 3 -substituted tertiary propargylic alcohols based on three retrosynthetic approaches, namely one trifluoromethylation approacha nd two building-block strategies.T he general challenges that are involved in the construction of aC F 3 -substituted tetrasubstituted stereogenic carbon speciesa re highlighted and possible future directions in the field are discussed.

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Catalytic asymmetric synthesis of CF₃-substituted tertiary propargylic alcohols via direct aldol reaction of α-N₃amide

Abstract: The catalyst comprising Cu(ii)/chiral hydroxamic acid was found to play a bifunctional role in the direct aldol reaction of α-N3 amide to alkynyl CF3 ketones.

Cited by 64 publications

References 115 publications

Synthesis of Extended Bipyridine‐proline Chiral Catalysts and Resulting Effects on the Asymmetric Aldol Reactions of Bulkier Aldehyde Derivatives with Cyclohexanone

Synthesis of Extended Bipyridine‐proline Chiral Catalysts and Resulting Effects on the Asymmetric Aldol Reactions of Bulkier Aldehyde Derivatives with Cyclohexanone

Direct Catalytic Asymmetric Aldol Reaction of α‐Alkoxyamides to α‐Fluorinated Ketones

Catalytic Asymmetric Synthesis of α‐Trifluoromethylated Carbinols: A Case Study of Tertiary Propargylic Alcohols

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Catalytic asymmetric synthesis of CF3-substituted tertiary propargylic alcohols via direct aldol reaction of α-N3amide

Abstract: The catalyst comprising Cu(ii)/chiral hydroxamic acid was found to play a bifunctional role in the direct aldol reaction of α-N3 amide to alkynyl CF3 ketones.

Cited by 64 publications

References 115 publications

Synthesis of Extended Bipyridine‐proline Chiral Catalysts and Resulting Effects on the Asymmetric Aldol Reactions of Bulkier Aldehyde Derivatives with Cyclohexanone

Synthesis of Extended Bipyridine‐proline Chiral Catalysts and Resulting Effects on the Asymmetric Aldol Reactions of Bulkier Aldehyde Derivatives with Cyclohexanone

Direct Catalytic Asymmetric Aldol Reaction of α‐Alkoxyamides to α‐Fluorinated Ketones

Catalytic Asymmetric Synthesis of α‐Trifluoromethylated Carbinols: A Case Study of Tertiary Propargylic Alcohols

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Catalytic asymmetric synthesis of CF₃-substituted tertiary propargylic alcohols via direct aldol reaction of α-N₃amide