Synthesis and Biological Activities of Conformationally Restricted Cyclopentenyl-Glutamate Analogues

Ung, Alison T.; Schäfer, Karl; Lindsay, Karl B.; Pyne, Stephen G.; Amornraksa, Kitti; Wouters, Ria; Linden, Ilse Van der; Biesmans, Ilse; Lesage, Anne; Skelton, Brian W.; White, Allan H.

doi:10.1021/jo010864i

Cited by 48 publications

(34 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[5a] further elegant developments and extensions of the chemistry based on nucleophilic phosphine catalysis have been widely pursued by many other groups [10] and this chemistry is enriching the arsenal of chemical reactions. [11] The commonly accepted mechanism for the phosphinecatalyzed [3 + 2] cycloaddition reaction of allenoates and activated alkenes is given in Scheme 2.…”

Section: Introductionmentioning

confidence: 99%

“…Despite the widespread application of phosphine-catalyzed [3 + 2] cycloaddition reactions and the continuing development of phosphine-catalyzed organocatalysis [10,11] and allene chemistry, [12] the detailed mechanism of phosphinecatalyzed [3 + 2] cycloaddition reactions has not been investigated experimentally or theoretically. To the best of our knowledge only a few studies have been conducted to rationalize the regioselectivity of these reactions by scrutinizing the [3 + 2] cycloaddition transition-state structures located by theoretical calculations.…”

Section: Introductionmentioning

confidence: 99%

“…These mechanistic studies give an insight into the chemistry of nucleophilic phosphine organocatalysis and related reactions in general. [10] In addition, these mechanistic insights will act as a guide in the future design of new reactions and new chiral organocatalysts. Furthermore, the results of this study will prompt chemists to rethink the role of a trace amount of water in "anhydrous" organic reactions that involve [1,n]-hydrogen shifts.…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, the results of this study will prompt chemists to rethink the role of a trace amount of water in "anhydrous" organic reactions that involve [1,n]-hydrogen shifts. [10] …”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Mechanism, Regioselectivity, and the Kinetics of Phosphine‐Catalyzed [3+2] Cycloaddition Reactions of Allenoates and Electron‐Deficient Alkenes

Liang

Liu

Xia

et al. 2008

Chemistry A European J

352

151

View full text Add to dashboard Cite

With the aid of computations and experiments, the detailed mechanism of the phosphine-catalyzed [3+2] cycloaddition reactions of allenoates and electron-deficient alkenes has been investigated. It was found that this reaction includes four consecutive processes: 1) In situ generation of a 1,3-dipole from allenoate and phosphine, 2) stepwise [3+2] cycloaddition, 3) a water-catalyzed [1,2]-hydrogen shift, and 4) elimination of the phosphine catalyst. In situ generation of the 1,3-dipole is key to all nucleophilic phosphine-catalyzed reactions. Through a kinetic study we have shown that the generation of the 1,3-dipole is the rate-determining step of the phosphine-catalyzed [3+2] cycloaddition reaction of allenoates and electron-deficient alkenes. DFT calculations and FMO analysis revealed that an electron-withdrawing group is required in the allene to ensure the generation of the 1,3-dipole kinetically and thermodynamically. Atoms-in-molecules (AIM) theory was used to analyze the stability of the 1,3-dipole. The regioselectivity of the [3+2] cycloaddition can be rationalized very well by FMO and AIM theories. Isotopic labeling experiments combined with DFT calculations showed that the commonly accepted intramolecular [1,2]-proton shift should be corrected to a water-catalyzed [1,2]-proton shift. Additional isotopic labeling experiments of the hetero-[3+2] cycloaddition of allenoates and electron-deficient imines further support this finding. This investigation has also been extended to the study of the phosphine-catalyzed [3+2] cycloaddition reaction of alkynoates as the three-carbon synthon, which showed that the generation of the 1,3-dipole in this reaction also occurs by a water-catalyzed process.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…Furthermore, the results of this study will prompt chemists to rethink the role of a trace amount of water in "anhydrous" organic reactions that involve [1,n]-hydrogen shifts. [10] …”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Mechanism, Regioselectivity, and the Kinetics of Phosphine‐Catalyzed [3+2] Cycloaddition Reactions of Allenoates and Electron‐Deficient Alkenes

Liang

Liu

Xia

et al. 2008

Chemistry A European J

352

151

View full text Add to dashboard Cite

show abstract

“…7 We also reported the synthesis of the 4-phenyl substituted derivative, rac-4, and its aryl substituted derivatives. Compound rac-4 is a selective antagonist at mGluR2…”

Section: Introductionmentioning

confidence: 99%