Diastereodivergent Addition of Allenylzincs to Aryl Glyoxylates

Hameury, Thomas; Guillemont, Jérôme; Hijfte, Luc Van; Bellosta, Véronique; Cossy, Janine

doi:10.1021/ol900494g

Cited by 35 publications

(25 citation statements)

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“…Interestingly, the Et 2 Zn-mediated reaction displayed a predominantly trans relationship between ethynyl and OH groups in the resulting 2-alkynylcyclopentanol products, suggesting the intervention of open transition states. [12] This interpretation contrasts with observations made in the related intermolecular reactions of allenylzinc (and allenylindium) reagents generated in the same fashion, which have been widely reported to participate in intermolecular carbonyl addition reactions [1][2][3] in which, with few exceptions, [14,15] the observed very high stereoselectivity was consistent with the involvement of chelated transition structures. [16] Two features of those trans-selective intramolecular reactions should be noticed.…”

Section: Introductioncontrasting

confidence: 79%

Catalyst‐ and Solvent‐Dependent Stereodivergence in the Intramolecular Et₂Zn/Pd⁰‐Promoted Carbonyl Propargylation: Mechanistic Implications

Arrate

Durana

Lorenzo

et al. 2013

Chemistry A European J

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Carbonyl-tethered propargylic benzoates undergo intramolecular carbonylpropargylation upon treatment with Et2 Zn in the presence of a catalytic amount of Pd(0) with the formation of 2-alkynylcyclopentanol products. A ligand/solvent effect on the cis/trans selectivity (referring to the relative positions of alkynyl and OH groups) of ring-closure has been found. In a non-coordinating solvent (benzene), increasing the electron-donating ability of the phosphine ligand (while decreasing its dissociation ability) leads to an increased tendency towards the trans product. On the other hand, the combination of a coordinating solvent (THF) and PPh3 , an easily dissociated phosphine, results in the exclusive formation of cis products. Experimental and computational results are compatible with a divergent behavior of an allenylethylpalladium intermediate that partitions between competitive carbonyl-addition and transmetalation pathways, each leading to a different diastereoisomer. These results also suggest that the dissociating ability of the phosphine regulates that behavior.

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Section: Introductioncontrasting

confidence: 79%

Catalyst‐ and Solvent‐Dependent Stereodivergence in the Intramolecular Et₂Zn/Pd⁰‐Promoted Carbonyl Propargylation: Mechanistic Implications

Arrate

Durana

Lorenzo

et al. 2013

Chemistry A European J

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“…ZnEt 2 serves as an efficient hydride donor, triggering the sequential Brook and Ireland-Claisen rearrangements, to afford the glycolic acid in 69% yield with good diastereoselectivity (Table 1, entry 5). The reduction of α-ketoesters with ZnEt 2 or EtMgBr has been previously reported; however, it is typically a minor byproduct to ethyl addition 9. Allyl zinc bromide and allenyl zinc bromide were useful triggers as well (Table 1, entries 6–10).…”

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confidence: 88%

Synthesis of γ,δ-Unsaturated Glycolic Acids via Sequenced Brook and Ireland−Claisen Rearrangements

Schmitt

Johnson

2010

Org. Lett.

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Organozinc, magnesium, and lithium nucleophiles initiate a Brook/Ireland-Claisen rearrangement sequence of allylic silyl glyoxylates resulting in formation of γ,δ-unsaturated α-silyloxy acids.New methods to produce the glycolic acid moiety continue to be important in the creation of small molecule building blocks. 1 γ,δ-Unsaturated glycolic acid derivatives represent a functional group-rich subset of substituted α-hydroxy acids with significant potential for further elaboration. The preparation of such compounds may be achieved via Ireland-Claisen rearrangement of allyl glycolate esters. 2 While the standard Ireland-Claisen rearrangement is performed by sequential enolization and silylation of allylic esters, alternative approaches to the requisite silyl ketene acetal have been reported. Methods include 1,4-addition to enoates, 3 silylene transfer followed by 6π-electrocyclization, 4 or by Rh-catalyzed reduction of enoates. 5 These methods allow for the generation of chiral products from achiral starting materials; however, a method that introduces multiple α-substituents in a single-pot process could potentially allow more rapid buildup of molecular complexity. An assessment of other Grignard reagents revealed that MeMgBr had potential as an effective nucleophile as it cleanly added to cinnamyl silyl glyoxylate 1a at 0 °C. In this case, Brook rearrangement did not occur below room temperature. When the reaction was allowed to warm, only decomposition was observed. Silyl ketene acetal formation was then attempted by addition of MeMgBr at 0 °C followed by warming to room temperature and addition of TMSCl; however, this also resulted in decomposition. Given that no TMS incorporation had occurred, we turned to TMSOTf, which induced the desired Ireland-Claisen rearrangement and provided the γ,δ-unsaturated glycolic acid 7 in 55% yield ( Organozinc nucleophiles were also found to be effective. ZnEt 2 serves as an efficient hydride donor, triggering the sequential Brook and Ireland-Claisen rearrangements, to afford the glycolic acid in 69% yield with good diastereoselectivity (Table 1, entry 5). The reduction of α-ketoesters with ZnEt 2 or EtMgBr has been previously reported; however, it is typically a minor byproduct to ethyl addition. 9 Allyl zinc bromide and allenyl zinc bromide were useful triggers as well (Table 1, entries 6-10).Substituted allylic zinc nucleophiles were also competent initiators. Methallyl zinc bromide provided the desired products with slightly diminished diastereoselectivity relative to allyl zinc bromide (Table 1, entries 11-12). The reaction was also tolerant of crotyl-and cinnamylzinc reagents; however, products were obtained as a complex mixture of diastereomers (not shown). Notably, none of the organozinc nucleophiles required silyl ketene acetal formation, as the zinc enolate underwent [3,3]-rearrangement spontaneously. Geranyl silyl glyoxylate 20 underwent the title transformation when treated with allenyl or allylic zinc bromides, providing glycolic acid derivatives in moderat...

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“…Recently, we reported on the synthesis of tertiary 2,3-diaryl-2-hydroxypentynoates 2 and 3 by diastereodivergent addition of allenylzincs to aryl glyoxylates 1 (Scheme 2). [5] Depending on the conditions used to generate the allenylzinc species [Scheme 2, Equation (1) and (2)], diastereomeric homopropargylic alcohols 2 and 3 were produced in good yields and diastereoselectivities. In order to utilize this method to prepare biologically active compounds, the synthetic potential of these tertiary alcohols was investigated through diverse transformations.…”

Section: Introductionmentioning

confidence: 99%

Reduction of Alkynyl α‐Hydroxy Esters: Stereoselective α‐Ketol Rearrangement

Hameury¹,

Bellosta²,

Guillemont³

et al. 2010

Eur J Org Chem

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Diastereodivergent Addition of Allenylzincs to Aryl Glyoxylates

Abstract: A diastereodivergent addition of allenylzincs to aryl glyoxylates was observed depending on the method used for the preparation of the allenylzinc reagent. The allenylzincs were prepared from propargylic benzoates in the presence of a palladium catalyst or by metalation of alkynes.

Cited by 35 publications

References 14 publications

Catalyst‐ and Solvent‐Dependent Stereodivergence in the Intramolecular Et₂Zn/Pd⁰‐Promoted Carbonyl Propargylation: Mechanistic Implications

Catalyst‐ and Solvent‐Dependent Stereodivergence in the Intramolecular Et₂Zn/Pd⁰‐Promoted Carbonyl Propargylation: Mechanistic Implications

Synthesis of γ,δ-Unsaturated Glycolic Acids via Sequenced Brook and Ireland−Claisen Rearrangements

Reduction of Alkynyl α‐Hydroxy Esters: Stereoselective α‐Ketol Rearrangement

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Diastereodivergent Addition of Allenylzincs to Aryl Glyoxylates

Abstract: A diastereodivergent addition of allenylzincs to aryl glyoxylates was observed depending on the method used for the preparation of the allenylzinc reagent. The allenylzincs were prepared from propargylic benzoates in the presence of a palladium catalyst or by metalation of alkynes.

Cited by 35 publications

References 14 publications

Catalyst‐ and Solvent‐Dependent Stereodivergence in the Intramolecular Et2Zn/Pd0‐Promoted Carbonyl Propargylation: Mechanistic Implications

Catalyst‐ and Solvent‐Dependent Stereodivergence in the Intramolecular Et2Zn/Pd0‐Promoted Carbonyl Propargylation: Mechanistic Implications

Synthesis of γ,δ-Unsaturated Glycolic Acids via Sequenced Brook and Ireland−Claisen Rearrangements

Reduction of Alkynyl α‐Hydroxy Esters: Stereoselective α‐Ketol Rearrangement

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Catalyst‐ and Solvent‐Dependent Stereodivergence in the Intramolecular Et₂Zn/Pd⁰‐Promoted Carbonyl Propargylation: Mechanistic Implications

Catalyst‐ and Solvent‐Dependent Stereodivergence in the Intramolecular Et₂Zn/Pd⁰‐Promoted Carbonyl Propargylation: Mechanistic Implications