Overlap Control of Carbanionoid Reactions. I. Stereoselectivity in Alkaline Epoxidation

Zimmerman, Howard E.; Singer, Lawrence A.; Thyagarajan, B. S.

doi:10.1021/ja01510a024

Cited by 93 publications

(24 citation statements)

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“…They argued that rotation about the C α –C β sigma bond of a β-hydroperoxy enolate intermediate (and stereochemical scrambling) was rapid relative to cleavage of the peroxyl O–O bond to form the oxirane ring. This analysis was consistent with a number of earlier observations by others concerning related processes,6 and has since been reinforced by studies of the peroxidation of different α,β-unsaturated carbonyl compounds with alkaline hydrogen peroxide in both protic and aprotic media 7. Clearly, a rationalization of the stereochemical outcomes of the transformations of Figure 1 could be framed quite differently for stepwise and concerted processes.…”

supporting

confidence: 89%

Anti-Selective Epoxidation of Methyl α-Methylene-β-tert-butyldimethylsilyloxycarboxylate Esters. Evidence for Stereospecific Oxygen Atom Transfer in a Nucleophilic Epoxidation Process

Švenda

Myers

2009

Org. Lett.

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Methyl α-methylene-β-tert-butyldimethylsilyloxycarboxylate esters are found to undergo diastereoselective epoxidation in the presence of potassium tert-butoxide-tert-butyl hydroperoxide to form anti products. In an effort to better understand mechanistic details of the transformation and the basis of diastereoselectivities observed, we studied the epoxidation of substrates with α-methylene groups containing (trans) deuterium labels and discovered that oxygen-atom transfer proceeds with ≥95% stereospecificity in all cases examined. These and other experiments suggest that the mechanism of epoxidation is not distinguishable from a concerted process.In the context of a problem in target-directed, complex synthesis we were led to explore the epoxidation of methyl α-methylene-β-hydroxycarboxylate esters and their hydroxyl-protected derivatives, and report here that the corresponding tert-butyldimethylsilyl ethers undergo efficient, anti-selective epoxidation with potassium tert-butylperoxide in tetrahydrofuran (THF). While syn-selective epoxidations of α-methylene-β-hydroxy-carboxylate esters have been reported, 1 a method for anti-selective epoxidation of this substrate class had not been described previously. Figure 1 are results of epoxidations of nine methyl α-methylene-β-tertbutyldimethyl-silyloxycarboxylate esters bearing different β-alkyl substituents. All transformations employed stoichiometric amounts of tert-butyl hydroperoxide and catalytic quantities of potassium tert-butoxide (0.1-0.3 equiv) in THF at 0 °C. 2 Substrates with dimethoxymethyl, benzyloxymethyl, or unsaturated β-substituents reacted relatively rapidly, while those with cyclohexyl, ethyl, or 2-benzyloxyethyl β-substituents reacted more slowly, and required distributed addition of as much as 0.3 equiv of potassium tert-butoxide to achieve complete conversion. All reactions were complete within 12 h at 0 °C, provided that care was taken to thoroughly dry all substrates, reagents, and solvents (see Supporting Information). As summarized in Figure 1, anti products were formed selectively in all cases. Substrates with unsaturated β-substituents were epoxidized with somewhat lower selectivities, which evidence suggests may be due in part to a stereoelectronic effect (vide infra). In an important early finding, Tanaka et al. showed that 1,2-disubstituted allylic alcohols undergo syn-selective epoxidation in the presence of vanadium acetylacetonate and tert-butyl hydroperoxide. 3 Later, Baylis-Hillman products were shown to undergo syn-selective epoxidation with both vanadium-and titanium-based reagents. 1 We used the latter method to obtain authentic samples of the syn diastereomers for two of the examples of Figure 1, with the results shown in eqs 1 and 2 below. Interestingly, but not unexpectedly, the rates of epoxidations mediated by potassium tert-butoxide and titanium tetraisopropoxide varied inversely with substrates bearing electron-donating and electron-withdrawing β-substituents. Substrates in Figure 1 with more electron-withdrawin...

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supporting

confidence: 89%

Anti-Selective Epoxidation of Methyl α-Methylene-β-tert-butyldimethylsilyloxycarboxylate Esters. Evidence for Stereospecific Oxygen Atom Transfer in a Nucleophilic Epoxidation Process

Švenda

Myers

2009

Org. Lett.

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“…Likewise, 1 H NMR spectra of compounds 2c-h indicated the presence of two isomers in equal amounts as shown by the existence of two oxirane proton signals. This proves the formation of the diazaspiro derivatives 2c-h as mixtures of diastereomers although according to the literature [17] the epoxidation of ,-unsaturated ketones with alkaline hydrogen peroxide is diastereoselective.…”

supporting

confidence: 62%

Novel synthesis of highly functionalized pyrazolone systems via rearrangement of 5-phenyl-1-oxa-5,6-diazaspiro[2.4]heptane-4,7-diones

Metwally

Mohamed

Moustafa

et al. 2011

Chem Heterocycl Comp

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“…With 9e and 9f, the electron-rich aryl rings failed to migrate in the absence of DMPU, 15 and it was possible to isolate products 15 resulting from carbolithiation without rearrangement, even in THF (entries [11][12][13][14][15][16]. Epimeric products were produced from (E)-and (Z)-9f.…”

mentioning

confidence: 99%

“…Evidently, both the carbolithiation and aryl migration steps are stereospecific, 16 since either inverting the double-bond geometry in the starting material or exchanging the substituents Ar 1 and Ar 2 changes the configuration of the products. The crystal structure of 14a indicates that the addition-migration process is mechanistically suprafacial.…”

mentioning

confidence: 99%

Tandem β-Alkylation−α-Arylation of Amines by Carbolithiation and Rearrangement of N-Carbamoyl Enamines (Vinyl Ureas)

et al. 2010

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Organolithiums add in an umpolung fashion to the beta-carbon of N-carbamoyl enamines (N-vinyl ureas). The reaction proceeds with syn diastereospecificity and provides urea-stabilized, configurationally defined organolithiums. Facilitated by coordinating solvents (THF or DMPU), these undergo intramolecular attack on an N'-aryl group, resulting in retentive arylation of the organolithium and hence overall addition of an alkyl or aryl group to both carbon atoms of the urea-substituted alkene. Facile deprotection in hot butanol permits the rapid, multicomponent construction of heavily substituted amines.

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Overlap Control of Carbanionoid Reactions. I. Stereoselectivity in Alkaline Epoxidation

Cited by 93 publications

References 0 publications

Anti-Selective Epoxidation of Methyl α-Methylene-β-tert-butyldimethylsilyloxycarboxylate Esters. Evidence for Stereospecific Oxygen Atom Transfer in a Nucleophilic Epoxidation Process

Anti-Selective Epoxidation of Methyl α-Methylene-β-tert-butyldimethylsilyloxycarboxylate Esters. Evidence for Stereospecific Oxygen Atom Transfer in a Nucleophilic Epoxidation Process

Novel synthesis of highly functionalized pyrazolone systems via rearrangement of 5-phenyl-1-oxa-5,6-diazaspiro[2.4]heptane-4,7-diones

Tandem β-Alkylation−α-Arylation of Amines by Carbolithiation and Rearrangement of N-Carbamoyl Enamines (Vinyl Ureas)

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