Access to Functionalized Quaternary Stereocenters via the Copper-Catalyzed Conjugate Addition of Monoorganozinc Bromide Reagents Enabled by <i>N</i>,<i>N-</i>Dimethylacetamide

Fulton, Tyler J.; Alley, Phebe L; Rensch, Heather R; Ackerman, Adriana M; Berlin, Cameron B; Krout, Michael R.

doi:10.1021/acs.joc.8b02201

Cited by 5 publications

(5 citation statements)

References 51 publications

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“…Monoorganozinc compounds exhibit excellent reactivity towards β,β-disubstituted enones in the presence of TMSCl and CuBr.DMS in polar solvent N,N-dimethylacetamide (DMA) at 0 to 23 °C to synthesize various cyclic functionalized β-quaternary ketones (Scheme 10). [20] The reaction can furnishes five-, six-, and seven-membered ring products in high yields. Monoorganozinc compounds can readily be obtained from alkyl bromides which participate in conjugate addition.…”

Section: Non-asymmetric Conjugate Additionmentioning

confidence: 99%

Alkylation of Electron‐Deficient Olefins through Conjugate Addition of Organozinc Reagents: An Update

Baruah¹,

Deb

2021

Eur J Org Chem

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This review focuses on the applications of organozinc reagents in conjugate addition reactions. Organozinc compounds are a class of organometallic reagent used in various reactions such as addition, substitution, and coupling reactions. The conjugate addition or 1, 4-addition is one of the most useful bond forming strategies used in organic synthesis since broad range of nucleophiles can be employed in the reaction. Addition of organozinc to electron-deficient olefins attracts synthetic chemists as it preferably undergoes conjugate addition over 1,2addition unlike other organometallic reagents, such as Grignard reagent or organolithium. Many natural products were also synthesized by applying the conjugate addition reaction of organozinc. Moreover, organozinc reagents have superior functional group compatibility and can be easily prepared relative to other organometallic compounds. Consequently, conjugate additions of organozinc reagents were highly studied and having a review on it is very important at present. Though a few reviews are available, they either do not focus directly on the organozinc reagents or not on the conjugate addition. We hope that this review article will be of great use to organic researchers.

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Section: Non-asymmetric Conjugate Additionmentioning

confidence: 99%

Alkylation of Electron‐Deficient Olefins through Conjugate Addition of Organozinc Reagents: An Update

Baruah¹,

Deb

2021

Eur J Org Chem

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“…36−38 Translation of this reactivity to catalytic manifolds, while promising, is currently limited in scope to simple benzylic nucleophiles and cyclic enones. 39 Similarly, conjugate allylation of enones with organometallic reagents (Cu, 40−42 In, 43,44 Ba 45 ) is substrate-controlled, affording mixtures of 1,2-and 1,4-addition products. Selectivity is further complicated using 1,3-disubstituted allyl reagents due to competing αand γ-addition.…”

Section: ■ Backgroundmentioning

confidence: 99%

“…The most-developed approach to these products is conjugate addition under conditions to trap the enolate as the silyl enol ether, but this can be challenging for certain substitution patterns and functional groups. For example, reliable conjugate benzylation necessitates the use of excess preformed, thermally unstable organocopper reagents (Scheme A). − Translation of this reactivity to catalytic manifolds, while promising, is currently limited in scope to simple benzylic nucleophiles and cyclic enones . Similarly, conjugate allylation of enones with organometallic reagents (Cu, − In, , Ba) is substrate-controlled, affording mixtures of 1,2- and 1,4-addition products.…”

Section: Introductionmentioning

confidence: 99%

Ligand–Metal Cooperation Enables Net Ring-Opening C–C Activation/Difunctionalization of Cyclopropyl Ketones

et al. 2023

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Reactions that cleave C–C bonds and enable functionalization at both carbon sites are powerful strategic tools in synthetic chemistry. Stereodefined cyclopropyl ketones have become readily available and would be an ideal source of 3-carbon fragments, but general approaches to net C–C activation/difunctionalization are unknown. Herein, we demonstrate the cross-coupling of cyclopropyl ketones with organozinc reagents and chlorotrimethylsilane to form 1,3-difunctionalized, ring-opened products. A combination of experimental and theoretical studies rules out more established mechanisms and sheds light on how cooperation between the redox-active terpyridine (tpy) ligand and the nickel atom enables the C–C bond activation step. The reduced (tpy·–)NiI species activates the C–C bond via a concerted asynchronous ring-opening transition state. The resulting alkylnickel(II) intermediate can then be engaged by aryl, alkenyl, and alkylzinc reagents to furnish cross-coupled products. This allows quick access to products that are difficult to make by conjugate addition methods, such as β-allylated and β -benzylated enol ethers. The utility of this approach is demonstrated in the synthesis of a key (±)-taiwaniaquinol B intermediate and the total synthesis of prostaglandin D1.

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“…[36][37][38] Translation of this reactivity to catalytic manifolds, while promising, is currently limited in scope to simple benzylic nucleophiles and cyclic enones. 39 Similarly, conjugate allylation of enones with organometallic reagents (Cu, [40][41][42] In, 43,44 Ba 45 ) is substrate controlled, affording mixtures of 1,2-and 1,4-addition products. Selectivity is further complicated using 1,3-disubstituted allyl reagents due to competing α-and γ-addition.…”

Section: Introductionmentioning

confidence: 99%

Ligand-Metal Cooperation Enables Net C–C Activation Cross-Coupling Reactivity of Cyclopropyl Ketones

Gilbert

Trenerry

Longley

et al. 2023

Preprint

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Reactions that cleave C–C bonds and enable functionalization at both carbon sites are powerful strategic tools in synthetic chemistry. Stereodefined cyclopropyl ketones have become readily available and would be an ideal source of 3-carbon fragments, but general approaches to net C–C activation / difunctionalization are unknown. Herein we demonstrate the cross-coupling of cyclopropyl ketones with organozinc reagents and chlorotrimethylsilane to form 1,3-difunctionalized, ring-opened products. A combination of experimental and theoretical studies rule out more established mechanisms and shed light on how cooperation between the redox-active terpyridine (tpy) ligand and the nickel atom enables the C–C bond activation step. The reduced (tpy•–)NiI species activates the C–C bond via a concerted asynchronous ring-opening transition state. The resulting alkylnickel(II) intermediate can then be engaged by aryl-, alkenyl-, and alkylzinc reagents to furnish cross-coupled products. This allows quick access to products that are difficult to make by conjugate addition methods, such as β-allylated and β-benzylated enol ethers. The utility of this approach is demonstrated in the synthesis of a key (±)-taiwaniaquinol B intermediate and the total synthesis of prostaglandin D1.

show abstract

Access to Functionalized Quaternary Stereocenters via the Copper-Catalyzed Conjugate Addition of Monoorganozinc Bromide Reagents Enabled by N,N-Dimethylacetamide

Cited by 5 publications

References 51 publications

Alkylation of Electron‐Deficient Olefins through Conjugate Addition of Organozinc Reagents: An Update

Alkylation of Electron‐Deficient Olefins through Conjugate Addition of Organozinc Reagents: An Update

Ligand–Metal Cooperation Enables Net Ring-Opening C–C Activation/Difunctionalization of Cyclopropyl Ketones

Ligand-Metal Cooperation Enables Net C–C Activation Cross-Coupling Reactivity of Cyclopropyl Ketones

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