Forging Fluorine‐Containing Quaternary Stereocenters by a Light‐Driven Organocatalytic Aldol Desymmetrization Process

Cuadros, Sara; Dell’Amico, Luca; Melchiorre, Paolo

doi:10.1002/ange.201706763

Cited by 25 publications

(5 citation statements)

References 67 publications

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“…According to the reaction design shown in Fig. 2c, we began with an investigation of the model reaction for the construction of bridged tricyclo[5.2.1.0 1,5 ]decanes using the 1,3-cyclopentanedione tethered 1,6-enyne 1a as substrate, which can be easily prepared by a two-step sequence consisting of the reductive Knoevenagel condensation of commercially available cyclopentane-1,3-dione with alkynals 51,52 followed by allylation with allyl halides. The reaction was first conducted with 10 mol % of Ni(OAc) 2 .4H 2 O and 12 mol % of (S)-phenyl-Phox (L1) as catalyst in MeCN.…”

Section: Resultsmentioning

confidence: 99%

Synthesis of bridged tricyclo[5.2.1.01,5]decanes via nickel-catalyzed asymmetric domino cyclization of enynones

et al. 2020

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The restricted availability, expense and toxicity of precious metal catalysts such as rhodium and palladium challenge the sustainability of synthetic chemistry. As such, nickel catalysts have garnered increasing attention as replacements for enyne cyclization reactions. On the other hand, bridged tricyclo[5.2.1.0 1,5 ]decanes are found as core structures in many biologically active natural products; however, the synthesis of such frameworks with high functionalities from readily available precursors remains a significant challenge. Herein, we report a nickel-catalyzed asymmetric domino cyclization reaction of enynones, providing rapid and modular synthesis of bridged tricyclo[5.2.1.0 1,5 ]decane skeletons with three quaternary stereocenters in good yields and remarkable high levels of regio-and enantioselectivities (92-99% ee).

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Section: Resultsmentioning

confidence: 99%

Synthesis of bridged tricyclo[5.2.1.01,5]decanes via nickel-catalyzed asymmetric domino cyclization of enynones

et al. 2020

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“…52,53 The group of Melchiorre made a remarkable contribution to this field, not only by developing an asymmetric method and for obtaining chiral tetralines with high level of enantiocontrol, but also by exploring other reactions of photogenerated o-quinodimethanes. 54,55 Until the present, photochemical metal-free synthesis of phthalazines via photogenerated o-quinodimethanes has failed. 56 While a tetrahydrophthalazine derivative was observed in reaction of diethyl azodicarboxylate with photodiene of o-methyl benzophenone, it could, however, not be converted into a phthalazine.…”

Section: Resultsmentioning

confidence: 99%

Light-driven catalyst-free access to phthalazines: Merging two metal-free domino reactions in one-pot

Guryev

Schuster

Tsogoeva

2022

Preprint

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We report the development of an unprecedented metal-free four-step one-pot synthetic strategy to access high-value functionalized phthalazines using o-methyl benzophenones as starting compounds. Combination of a light-mediated enolization of o-methyl benzophenones/Diels-Alder reaction domino process with a subsequent deprotection/aromatization domino reaction in one-pot leads to sustainable and efficient organic synthesis. The tangible advantages, i.e. absence of catalysts or additives, utilization of commercially available and/or easily accessible substrates, mild reaction conditions, simplicity, and single work-up procedure, make this combined process highly appealing for the direct construction of various 1-aryl-phthalazines.

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“…Motivated by the potential applications of organofluorine compounds in a variety of scientific disciplines 26 , 27 , the scope of α-bromo-α-fluoroketones 5 was examined next (Fig. 3 ).…”

Section: Resultsmentioning

confidence: 99%

Formal enantioconvergent substitution of alkyl halides via catalytic asymmetric photoredox radical coupling

Li¹,

Kong²,

Qiao³

et al. 2018

Nat Commun

138

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Classic nucleophilic substitution reactions (SN1 and SN2) are not generally amenable to the enantioselective variants that use simple and racemic alkyl halide electrophiles. The merging of transition metal catalysis and radical chemistry with organometallic nucleophiles is a versatile method for addressing this limitation. Here, we report that visible light-driven catalytic asymmetric photoredox radical coupling can act as a complementary and generic strategy for the enantioconvergent formal substitution of alkyl haldies with readily available and bench-stable organic molecules. Single-electron reductive debrominations of racemic α-bromoketones generate achiral alkyl radicals that can participate in asymmetric Csp3–Csp3 bonds forming cross-coupling reactions with α-amino radicals derived from N-aryl amino acids. A wide range of valuable enantiomerically pure β2- and β2,2-amino ketones were obtained in satisfactory yields with good-to-excellent enantioselectivities by using chiral phosphoric acid catalysts to control the stereochemistry and chemoselectivity. Fluoro-hetero-quaternary and full-carbon quaternary stereocenters that are challenging to prepare were successfully constructed.

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Forging Fluorine‐Containing Quaternary Stereocenters by a Light‐Driven Organocatalytic Aldol Desymmetrization Process

Cited by 25 publications

References 67 publications

Synthesis of bridged tricyclo[5.2.1.01,5]decanes via nickel-catalyzed asymmetric domino cyclization of enynones

Synthesis of bridged tricyclo[5.2.1.01,5]decanes via nickel-catalyzed asymmetric domino cyclization of enynones

Light-driven catalyst-free access to phthalazines: Merging two metal-free domino reactions in one-pot

Formal enantioconvergent substitution of alkyl halides via catalytic asymmetric photoredox radical coupling

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