Highly Enantioselective Construction of Tricyclic Derivatives by the Desymmetrization of Cyclohexadienones

Martín‐Santos, Cecilia; Jarava‐Barrera, Carlos; Pozo, Sandra del; Parra, Alejandro; Díaz‐Tendero, Sergio; Mas‐Ballesté, Rubén; Cabrera, Silvia; Alemán, José V.

doi:10.1002/ange.201402853

Cited by 25 publications

(5 citation statements)

References 58 publications

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“…The asymmetric synthesis of a collection of tricyclic derivatives 204 was developed by Alemán and collaborators via an aminocatalyzed desymmetrization reaction involving ad hoc prepared cyclohexadienone/enals 203 ( Scheme 56 , eq 2). 156 DFT-based calculations and control experiments showed that this transformation proceeds via an asynchronous eliminative [4 + 2] cycloaddition ( endo transition state) and not a stepwise Michael/aldol/elimination cascade reaction.…”

Section: Vinylogous Aldehydesmentioning

confidence: 99%

New Developments of the Principle of Vinylogy as Applied to π-Extended Enolate-Type Donor Systems

et al. 2020

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The principle of vinylogy states that the electronic effects of a functional group in a molecule are possibly transmitted to a distal position through interposed conjugated multiple bonds. As an emblematic case, the nucleophilic character of a π-extended enolate-type chain system may be relayed from the legitimate α-site to the vinylogous γ, ε, ..., ω remote carbon sites along the chain, provided that suitable HOMO-raising strategies are adopted to transform the unsaturated pronucleophilic precursors into the reactive polyenolate species. On the other hand, when “unnatural” carbonyl ipso -sites are activated as nucleophiles (umpolung), vinylogation extends the nucleophilic character to “unnatural” β, δ, ... remote sites. Merging the principle of vinylogy with activation modalities and concepts such as iminium ion/enamine organocatalysis, NHC-organocatalysis, cooperative organo/metal catalysis, bifunctional organocatalysis, dicyanoalkylidene activation, and organocascade reactions represents an impressive step forward for all vinylogous transformations. This review article celebrates this evolutionary progress, by collecting, comparing, and critically describing the achievements made over the nine year period 2010–2018, in the generation of vinylogous enolate-type donor substrates and their use in chemical synthesis.

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Section: Vinylogous Aldehydesmentioning

confidence: 99%

New Developments of the Principle of Vinylogy as Applied to π-Extended Enolate-Type Donor Systems

et al. 2020

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“…Recently, Alemán reported a straightforward method for the construction of tricyclic fused rings from a cyclohexadienone tethered alkenal by employing an organocatalyzed asymmetric desymmetrization strategy (Fig. 1b ) 14 . In this process, desymmetrization step involved the intramolecular [4 + 2] cycloaddition of chiral dienamine with a diastereotropic enone constructed tricyclic fused rings with three chiral centers.…”

Section: Introductionmentioning

confidence: 99%

Two-step synthesis of chiral fused tricyclic scaffolds from phenols via desymmetrization on nickel

et al. 2017

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Tricyclic furan derivatives with multiple chiral centers are ubiquitous in natural products. Construction of such tricyclic scaffolds in a stereocontrolled, step-economic, and atom-economic manner is a key challenge. Here we show a nickel-catalyzed highly enantioselective synthesis of hydronaphtho[1,8-bc]furans with five contiguous chiral centers via desymmetrization of alkynyl-cyclohexadienone by oxidative cyclization and following formal [4 + 2] cycloaddition processes. Alkynyl-cyclohexadienone was synthesized in one step from easily accessible phenols. This reaction represents excellent chemo-selectivity, regio-selectivity, diastereo-selectivity, and enantio-selectivity (single diastereomer, up to 99% ee). An extraordinary regioselectivity in the formal [4 + 2] cycloaddition step with enones revealed the diverse reactivity of the nickelacycle intermediate. Desymmetrization of alkynyl-cyclohexadienones via oxidative cyclization on nickel was supported by the isolation of a nickelacycle from a stoichiometric reaction. Enantioenriched tricyclic products contain various functional groups such as C=O and C=C. The synthetic utility of these products was demonstrated by derivatization of these functional groups.

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“…After that, Aleman et al . performed an intramolecular [4+2] cycloaddition of cyclohexadienones 15 containing α,β‐unsaturated aldehydes at remote position [14] . It involved a formal conjugated Michael addition/aldol reaction sequence by means of dienamine catalysis, which was also promoted by Jørgensen‐Hayashi organocatalyst IIb .…”

Section: Desymmetrization Via Organocatalytic Enantioselective Intramolecular Michael Reaction (Immr)mentioning

confidence: 99%

Organocatalytic Enantioselective Intramolecular (Hetero)Michael Additions in Desymmetrization Processes

et al. 2021

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The organocatalytic enantioselective desymmetrization reaction by means of an intramolecular (hetero)Michael addition is a useful strategy for the creation of complex carbo-and heterocycles with the generation of multiple stereocenters in a very simple manner. The intramolecular addition of carbon, oxygen and nitrogen nucleophiles to prochiral substrates bearing electronically deficient olefins takes place in the presence of organocatalysts, such as chiral primary and secondary amines, NHCs, ureas, thioureas, and BINOL phosphoric acid derivatives, reaching high levels of diastereo-and enantioselectivity. The main bottleneck of this methodology is the design and synthesis of the starting materials, which compromises its application. To date, the majority of examples are related to the use of 1,4-cyclohexanedione derivatives.

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Highly Enantioselective Construction of Tricyclic Derivatives by the Desymmetrization of Cyclohexadienones

Cited by 25 publications

References 58 publications

New Developments of the Principle of Vinylogy as Applied to π-Extended Enolate-Type Donor Systems

New Developments of the Principle of Vinylogy as Applied to π-Extended Enolate-Type Donor Systems

Two-step synthesis of chiral fused tricyclic scaffolds from phenols via desymmetrization on nickel

Organocatalytic Enantioselective Intramolecular (Hetero)Michael Additions in Desymmetrization Processes

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