Enantioselective copper-catalyzed conjugate additions of in situ generated organozirconium reagents to N -heterocyclic Michael acceptors

Némethová, Ivana; Bilka, Stanislav; Šebesta, Radovan

doi:10.1016/j.jorganchem.2017.12.042

Cited by 6 publications

(6 citation statements)

References 36 publications

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“…Among the earliest examples of ACAs to heterocyclic Michael acceptors were additions of dialkyl zinc reagents to unsaturated lactams, [11] and lactones, furanones, and pyranones developed by Hoveyda [12] . Feringa, Dieter as well as our laboratory have developed methodologies for Cu‐catalyzed asymmetric conjugate additions to N ‐protected piperidones using dialkylzinc [13] and alkylzirconium reagents [14] . However, there is a need for complementary reagents that enable access to different functionalities and possess higher reactivity to balance out the lower reactivity of the heterocyclic substrate.…”

Section: Methodsmentioning

confidence: 99%

“…[12] Feringa, Dieter as well as our laboratory have developed methodologies for Cu-catalyzed asymmetric conjugate additions to N-protected piperidones using dialkylzinc [13] and alkylzirconium reagents. [14] However, there is a need for complementary reagents that enable access to different functionalities and possess higher reactivity to balance out the lower reactivity of the heterocyclic substrate. Grignard reagents, as considerably reactive organometallic nucleophiles, may fulfill this role.…”

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confidence: 99%

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Asymmetric Tandem Conjugate Addition and Reaction with Carbocations on Unsaturated Heterocycles

et al. 2022

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Heterocycles possessing multiple substituents and stereogenic centers are important structural motifs in many compounds of interest. We present here stereoselective tandem transformation based on Cu‐catalyzed conjugate addition of Grignard reagents to heterocyclic Michael acceptors, which is followed by one‐pot trapping of in situ formed enolates with stabilized carbocations or their equivalents. The transformations are highly enantio‐ and diastereoselective with Josiphos‐type ferrocene ligand. The reaction of chiral metal enolates with onium compounds allows the installation of structurally attractive substituents on chromenone or piperidinone core. Moreover, cycloheptatrienyl and benzodithiolyl substituents can be further modified, thus expanding synthetic possibilities of this methodology.

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Section: Methodsmentioning

confidence: 99%

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confidence: 99%

Asymmetric Tandem Conjugate Addition and Reaction with Carbocations on Unsaturated Heterocycles

et al. 2022

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“…Organozirconium compounds are another class of organometallic reagents that have been used widely in the synthesis of complex molecules. Recently, Fletcher and co-workers demonstrated the applicability of a hydrozirconation in the ACA reaction to non-heterocyclic conjugated substrates [22][23][24][25][26], while the Šebesta group was the first to report the copper-catalysed addition of organozirconium reagents to N-substituted 2,3dehydro-4-piperidones (Scheme 4A) [27]. In the latter work, the organozirconium reagents were generated first in situ by the hydrozirconation of alkenes.…”

Section: Review Copper-catalysed C-c Bond-forming Reactions At the Hementioning

confidence: 99%

Copper-catalysed alkylation of heterocyclic acceptors with organometallic reagents

Guo¹,

Harutyunyan²

2020

Beilstein J. Org. Chem.

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Copper-catalysed asymmetric C–C bond-forming reactions using organometallic reagents have developed into a powerful tool for the synthesis of complex molecules with single or multiple stereogenic centres over the past decades. Among the various acceptors employed in such reactions, those with a heterocyclic core are of particular importance because of the frequent occurrence of heterocyclic scaffolds in the structures of chiral natural products and bioactive molecules. Hence, this review focuses on the progress made over the past 20 years for heterocyclic acceptors.

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“…62 Our team has shown that aza-heterocyclic Michael acceptors are among the most challenging substrates for the ACA of organozirconium compounds. 63 If Ts-protected lactams were used, the enantioselectivity of the reaction did not surpass 64% ee and this level of stereoinduction was not broadly applicable. On the other hand, the low reactivity of protected dihydropiperidones 40 prevented the formation of the desired products 41 in satisfactory yields (Scheme 11).…”

Section: Short Review Synthesismentioning

confidence: 99%

Are Organozirconium Reagents Applicable in Current Organic Synthesis?

Némethová

Šebesta

2020

Synthesis

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The search for mild, user-friendly, easily accessible, and robust organometallic reagents is an important feature of organometallic chemistry. Ideally, new methodologies employing organometallics should be developed with respect to practical applications in syntheses of target compounds. In this short review, we investigate if organozirconium reagents can fulfill these criteria. Organozirconium compounds are typically generated via in situ hydrozirconation of alkenes or alkynes with the Schwartz reagent. Alkyl and alkenylzirconium reagents have proven to be convenient in conjugate additions, allylic substitutions, cross-coupling reactions, and additions to carbonyls or imines. Furthermore, the Schwartz reagent itself is a useful reducing agent for polar functional groups.1 Introduction2 Synthesis and Generation of the Schwartz Reagent3 Structure and Properties of Cp2Zr(H)Cl4 Reactivity of Organozirconium Reagents4.1 Asymmetric Conjugate Addition4.2 Asymmetric Allylic Alkylations4.3 Desymmetrization Reactions4.4 Cross-Coupling Reactions4.5 1,2-Additions5 Conclusions

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Enantioselective copper-catalyzed conjugate additions of in situ generated organozirconium reagents to N -heterocyclic Michael acceptors

Cited by 6 publications

References 36 publications

Asymmetric Tandem Conjugate Addition and Reaction with Carbocations on Unsaturated Heterocycles

Asymmetric Tandem Conjugate Addition and Reaction with Carbocations on Unsaturated Heterocycles

Copper-catalysed alkylation of heterocyclic acceptors with organometallic reagents

Are Organozirconium Reagents Applicable in Current Organic Synthesis?

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