<sup>13</sup>C Kinetic Isotope Effects for the Addition of Lithium Dibutylcuprate to Cyclohexenone. Reductive Elimination Is Rate-Determining

Frantz, Doug E.; Singleton, Daniel A.; Snyder, James P.

doi:10.1021/ja9636348

Cited by 113 publications

(84 citation statements)

References 21 publications

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“…Based on a study of kinetic isotope effects, the Cu does not become s-bonded to the a-carbon of the enone in the rate-determining step, as it would in the addition of RÀCu across the double bond. [65] Synthetic considerations: Among the decisions the synthetic chemist must make about organocopper reactions are the copper(i) precursor (CuI, CuBr, CuBr´DMS, CuCN), the active organometallic (RLi, RMgX, RZnX, RNa), the stoichiometry (catalytic Cu, 1:1, 2:1, b 2:1 RLi), the solvent (THF, ether, DMS, dichloromethane), the additive (TMSCl, HMPA, phosphine, Lewis acid), and the dummy ligand (alkynyl, thienyl, hetero, trimethylsilylmethyl), in addition to experimental variables such as cuprate excess, temperature, time, and work-up. [5,6,44] Many of these factors are interrelated, and it is difficult if not impossible to predict with certainty which of the many kinds of organocopper reagents will be optimal for a particular substrate.…”

Section: Reactions With Cyimentioning

confidence: 99%

Re-evaluation of Organocuprate Reactivity: Logarithmic Reactivity Profiles for Iodo- versus Cyano-Gilman Reagents in the Reactions of Organocuprates with 2-Cyclohexenone and Iodocyclohexane

Bertz¹,

Chopra

Eriksson

et al. 1999

Chem. Eur. J.

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Iodo-Gilman reagents Me 2 -CuLi´LiI, Bu 2 CuLi´LiI, and BuThCuLi´LiI and cyano-Gilman reagents (ne Â e ªhigher order cyanocupratesº Me 2 CuLi´LiCN, Bu 2 CuLi´LiCN, and BuThCuLi´LiCN react with 2-cyclohexenone at various rates, which depend upon the R groups (Me, Bu, Th thienyl), Li salt (LiI vs. LiCN), solvent (ether vs. THF), and amount of trimethylsilyl chloride (TMSCl) additive. The effect of the Li salt (CuI vs. CuCN precursor) is less than that of solvent or TMSCl. The butylcuprate-iodocyclohexane reaction has also been examined as a function of Li salt, solvent, and TMSCl additive, and similar effects are observed. The reactivity matrix R with elements r i,j is a convenient way to store and present a large amount of relative reactivity data. Entry r i,j is the ratio of the rate with reagent i to the rate with reagent j, which we approximate by using yields measured after a short time (4 s). The logarithmic reactivity profile (LRP) provides an efficient means for determining yields under conditions where such comparisons are valid. The results of a large number of 4-point LRPs and related reactions are tabulated and analyzed to provide a clearer picture of organocuprate reactivity.

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Section: Reactions With Cyimentioning

confidence: 99%

Re-evaluation of Organocuprate Reactivity: Logarithmic Reactivity Profiles for Iodo- versus Cyano-Gilman Reagents in the Reactions of Organocuprates with 2-Cyclohexenone and Iodocyclohexane

Bertz¹,

Chopra

Eriksson

et al. 1999

Chem. Eur. J.

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“…[11 d, 15] The relative magnitude of the rate constants was also assessed (k 1 /k À1 1.5, k À1 b k 2 ). [13] Using their elegant method, Singleton et al recently determined the kinetic isotope effects in the conjugate addition to cyclohexenone and concluded that the rate-limiting step is CÀC bond formation by reductive elimination of a copper(iii) intermediate such as E. [16] This step must correspond to the Krauss/Smith second energy barrier (k 2 ).…”

Section: Introductionmentioning

confidence: 99%

Density Functional Studies on Conjugate Addition of (Me2CuLi)2 to Cyclohexenone: Stereoselectivity and Rate-Determining Step

Mori

Nakamura

1999

Chem. Eur. J.

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The reaction pathway of the conjugate addition of a dimeric cuprate (Me 2 CuLi) 2 to 2-cyclohexenone has been studied by means of the B3LYP hybrid density functional method, and intermediates and transition structures (TSs) on the potential surface of the reaction have been determined. A lithium/carbonyl coordination complex (CPli), a copper/olefin complex retaining a closed cuprate structure (CPcl), a copper/olefin complex with an open cuprate structure (CPop), and the TS of CÀC bond formation (TScc) have been located along the gas-phase pathway leading to the conjugate addition product (PD). We studied two diastereoisomeric pathways, and found that the pathway that results in the axial placement of the nucleophilic methyl group in the product was favored throughout the course of the reaction, except in the product complex. Thus, the stereoselectivity of the conjugate addition to cyclohexenone originates from the stereochemical preference of the final, ratelimiting C À C bond formation stage that mainly reflects the steric factors in the formation of 3-methylcyclohexanone enolate in its half-chair form (TSccax).Comparison of the calculated and experimental values for 13 C NMR chemical shift and kinetic isotope effects strongly suggests that the copper/olefin complex of the CPop structural type is the reactive intermediate that directly forms the product. Thus, the open complex CPop, rather than the closed complex CPcl hitherto considered, is a direct precursor of the product and crucial for the stereoselectivity of the conjugate addition. On the basis of theory and experiments, transition-state models for the conjugate addition to substituted cyclohexenones are provided.

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“…首先有机铜试剂与底物的碳碳双键(π 键)络合, 形成 π 化合物, 然后经过氧化加成, 形成三价有机铜中间体, 最后还原消除为烯醇盐和烷基铜. π 化合物在低温下用核磁数据可得到证实 [62] , 三价铜中间体的存在却没有直接证据, 但得到了量子化学计算的验证 [63] . Snyder [64] …”

Section: β-位具有手性中心的砜是有机合成中的一种重要unclassified

Recent Advances in Copper-Catalyzed Asymmetric Conjugate Addition of Grignard Reagents

Tang¹,

Ye²

2015

Chin. J. Org. Chem.

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Copper-catalyzed asymmetric 1,4-, 1,6-and 1,2-conjugate addition of Grignard reagents is an important method to build up a carbon chiral center, which exists in the key intermediates of many natural products and chiral drugs. In this paper, the copper-catalyzed asymmetric 1,4-, 1,6-and 1,2-conjugate addition of Grignard reagents to α,β-unsaturated compounds is summarized systematically, and such acceptors as α,β-unsaturated ketones, esters, lactones, aldehydes, thioesters as well as sulfones are involved. In addition, the mechanism of asymmetric 1,4-conjugate addition is also introduced.

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¹³C Kinetic Isotope Effects for the Addition of Lithium Dibutylcuprate to Cyclohexenone. Reductive Elimination Is Rate-Determining

Cited by 113 publications

References 21 publications

Re-evaluation of Organocuprate Reactivity: Logarithmic Reactivity Profiles for Iodo- versus Cyano-Gilman Reagents in the Reactions of Organocuprates with 2-Cyclohexenone and Iodocyclohexane

Re-evaluation of Organocuprate Reactivity: Logarithmic Reactivity Profiles for Iodo- versus Cyano-Gilman Reagents in the Reactions of Organocuprates with 2-Cyclohexenone and Iodocyclohexane

Density Functional Studies on Conjugate Addition of (Me2CuLi)2 to Cyclohexenone: Stereoselectivity and Rate-Determining Step

Recent Advances in Copper-Catalyzed Asymmetric Conjugate Addition of Grignard Reagents

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13C Kinetic Isotope Effects for the Addition of Lithium Dibutylcuprate to Cyclohexenone. Reductive Elimination Is Rate-Determining

Cited by 113 publications

References 21 publications

Re-evaluation of Organocuprate Reactivity: Logarithmic Reactivity Profiles for Iodo- versus Cyano-Gilman Reagents in the Reactions of Organocuprates with 2-Cyclohexenone and Iodocyclohexane

Re-evaluation of Organocuprate Reactivity: Logarithmic Reactivity Profiles for Iodo- versus Cyano-Gilman Reagents in the Reactions of Organocuprates with 2-Cyclohexenone and Iodocyclohexane

Density Functional Studies on Conjugate Addition of (Me2CuLi)2 to Cyclohexenone: Stereoselectivity and Rate-Determining Step

Recent Advances in Copper-Catalyzed Asymmetric Conjugate Addition of Grignard Reagents

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¹³C Kinetic Isotope Effects for the Addition of Lithium Dibutylcuprate to Cyclohexenone. Reductive Elimination Is Rate-Determining