Quantification of the Nucleophilic Reactivities of Cyclic β‐Keto Ester Anions

Corral-Bautista, Francisco; Mayr, Herbert

doi:10.1002/ejoc.201501107

Cited by 18 publications

(15 citation statements)

References 28 publications

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“…We obtained these parameters for 264 nucleophiles in different solvents for a total number of 341 data points from Mayr’s data set, which include 41 olefins, , 38 (hetero)aromatics, ,, 22 Si-enolates (silyl ketene acetals, silyl enol ethers), ,, 35 enamines, ,, 26 ylides, 5 NHCs, 31 anionic C-nucleophiles (carbanions), 67 N-nucleophiles (aliphatic amines, pyridines, imidazoles, etc. ), ,, 27 anionic N-nucleophiles, 41 O-nucleophiles (phenolates and carboxylates), , and 8 S-nucleophiles. , These were chosen over a nucleophilicity range of 35 N units in 7 different solvents (DCM, ACN, THF, acetone, DMF, DMSO, and water).…”

Section: Resultsmentioning

confidence: 99%

Nucleophilicity Prediction via Multivariate Linear Regression Analysis

2021

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The concept of nucleophilicity is at the basis of most transformations in chemistry. Understanding and predicting the relative reactivity of different nucleophiles is therefore of paramount importance. Mayr’s nucleophilicity scale likely represents the most complete collection of reactivity data, which currently includes over 1200 nucleophiles. Several attempts have been made to theoretically predict Mayr’s nucleophilicity parameters N based on calculation of molecular properties, but a general model accounting for different classes of nucleophiles could not be obtained so far. We herein show that multivariate linear regression analysis is a suitable tool for obtaining a simple model predicting N for virtually any class of nucleophiles in different solvents for a set of 341 data points. The key descriptors of the model were found to account for the proton affinity, solvation energies, and sterics.

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Section: Resultsmentioning

confidence: 99%

Nucleophilicity Prediction via Multivariate Linear Regression Analysis

2021

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“…The next focus is to probe suitable N , O -acetal-based conditions using an intermolecular variant (Scheme ). However, the activated N -lactoyl iminium species in situ generated from 41 under protonic or Lewis acidic conditions severely suffered from either double bond isomerization followed by recapture by methanol to produce 50 or tautomerization to form trans -enamide 51 , and was found to be reluctant to undergo Mannich addition with the lactonic nucleophile (for details, see the Supporting Information of ref ) . To devise a workaround, we became keenly aware of the alcohol exchange phenomenon of N , O -acetals under pyrolytic conditions reported by Ben-Ishai in the 1960s .…”

Section: Resultsmentioning

confidence: 99%

Landscape of Lankacidin Biomimetic Synthesis: Structural Revisions and Biogenetic Implications

et al. 2020

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In this report, a unified biomimetic approach to all known macrocyclic lankacidins is presented. By taking advantage of the thermolysis of N,O-acetal to generate the requisite N-acyl-1-azahexatriene species, we eventually realized the biomimetic Mannich macrocyclization, from which all of the macrocyclic lankacidins can be conquered by orchestrated desilylation. The reassignments of the reported structures of isolankacidinol (7 to 10) and the discovery of a recently isolated "lankacyclinol" found to be in fact 2,18-bis-epi-lankacyclinol (72) unraveled the previously underappreciated chemical diversity exhibited by the enzymatic macrocyclization. In addition, the facile elimination/decarboxylation/protonation process for the depletion of C1 under basic conditions resembling a physiological environment may implicate more undiscovered natural products with variable C2/C18 stereochemistries (i.e., 62, 73, and 75). The notable aspect provided by a biomimetic strategy is significantly reducing the step count compared with the two previous entries to macrocyclic lankacidins.

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“…Av arietyo fo ther arylsubstituted indanone-based ketoesters were all well tolerated, and gratifyingly the tetralonep roduct 3q could also be obtained in reasonable selectivity.S urprisingly,t he synthesis of the acyclic a-hydroxy-b-ketoester 3r was not possible under our base-free conditions. [25] When carrying out the above described H/D exchange NMR experiment on this startingm aterial (please compare with Figure 1f or starting material 2a), we found that in this specific case no H/D exchange takesp lace under base-free conditions, thus rationalizingt he missingr eactivity under our standard conditions. By adding an inorganic base the reaction proceeds well, but only with low enantioselectivity.…”

Section: Resultsmentioning

confidence: 99%

Bifunctional Ammonium Salt Catalyzed Asymmetric α‐Hydroxylation of β‐Ketoesters by Simultaneous Resolution of Oxaziridines

Novacek

Izzo

Vetticatt

et al. 2016

Chemistry A European J

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Chiral bifunctional urea-containing ammonium salts were found to be very efficient catalysts for asymmetric α-hydroxylation reactions of β-ketoesters with oxaziridines under base-free conditions. The reaction is accompanied by a simultaneous kinetic resolution of the oxaziridine and a plausible and so far unprecedented bifunctional transition-state model has been obtained by means of DFT calculations.

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Quantification of the Nucleophilic Reactivities of Cyclic β‐Keto Ester Anions

Cited by 18 publications

References 28 publications

Nucleophilicity Prediction via Multivariate Linear Regression Analysis

Nucleophilicity Prediction via Multivariate Linear Regression Analysis

Landscape of Lankacidin Biomimetic Synthesis: Structural Revisions and Biogenetic Implications

Bifunctional Ammonium Salt Catalyzed Asymmetric α‐Hydroxylation of β‐Ketoesters by Simultaneous Resolution of Oxaziridines

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