2928-12-3Relevant academic research and scientific papers
Sustainable electrochemical decarboxylative acetoxylation of aminoacids in batch and continuous flow
K?ckinger, Manuel,Hanselmann, Paul,Roberge, Dominique M.,Geotti-Bianchini, Piero,Kappe, C. Oliver,Cantillo, David
supporting information, p. 2382 - 2390 (2021/04/12)
Introduction of acetoxy groups to organic molecules is important for the preparation of many active ingredients and synthetic intermediates. A commonly used and attractive strategy is the oxidative decarboxylation of aliphatic carboxylic acids, which entails the generation of a new C(sp3)-O bond. This reaction has been traditionally carried out using excess amounts of harmful lead(iv) acetate. A sustainable alternative to stoichiometric oxidants is the Hofer-Moest reaction, which relies on the 2-electron anodic oxidation of the carboxylic acid. However, examples showing electrochemical acetoxylation of amino acids are scarce. Herein we present a general and scalable procedure for the anodic decarboxylative acetoxylation of amino acids in batch and continuous flow mode. The procedure has been applied to the derivatization of several natural and synthetic amino acids, including key intermediates for the synthesis of active pharmaceutical ingredients. Good to excellent yields were obtained in all cases. Transfer of the process from batch to a continuous flow cell signficantly increased the reaction throughput and space-time yield, with excellent product yields obtained even in a single-pass. The sustainability of the electrochemical protocol has been examined by evaluating its green metrics. Comparison with the conventional method demonstrates that an electrochemical approach has a significant positive effect on the greenness of the process.
Activity and specificity studies of the new thermostable esterase EstDZ2
Myrtollari, Kamela,Katsoulakis, Nikolaos,Zarafeta, Dimitra,Pavlidis, Ioannis V.,Skretas, Georgios,Smonou, Ioulia
, (2020/09/16)
In this paper, we study the activity and specificity of EstDZ2, a new thermostable carboxyl esterase of unknown function, which was isolated from a metagenome library from a Russian hot spring. The biocatalytic reaction employing EstDZ2 proved to be an efficient method for the hydrolysis of aryl p-, o- or m-substituted esters of butyric acid and esters of secondary alcohols. Docking studies revealed structural features of the enzyme that led to activity differences among the different substrates.
Base-catalyzed selective esterification of alcohols with unactivated esters
Zhang, Chunyan,Zhang, Guoying,Luo, Shizhong,Wang, Chunfu,Li, Huiping
supporting information, p. 8467 - 8471 (2018/12/01)
A practical and efficient base-catalyzed esterification has been developed for the facile synthesis of a broad range of esters from simple alcohols with unactivated tert-butyl esters. This protocol could be conducted at mild conditions, providing esters in high to excellent yields with good functional tolerance. Mechanistic studies provided evidence of an exchange of the tert-butyl alkoxide metal with the alcohol, producing a new alkoxide to participate in the transesterification reaction.
Asymmetric transesterification of secondary alcohols catalyzed by feruloyl esterase from Humicola insolens
Hatzakis, Nikos S.,Smonou, Ioulia
, p. 325 - 337 (2007/10/03)
A new asymmetric transesterification of secondary alcohols catalyzed by feruloyl esterase from Humicola insolens has been found. Although alcohols are not the natural substrates for this enzyme, a high R enantioselectivity was observed. Stereochemical studies showed that variations in substrate structure lead to strong variations in enantioselectivity. The highest enantioselectivities are obtained when the β-carbon of the secondary alcohol is tertiary or quaternary.
Transesterification/Acylation of Secondary Alcohols Mediated by N-Heterocyclic Carbene Catalysts
Singh, Rohit,Kissling, Rebecca M.,Letellier, Marie-Anne,Nolan, Steven P.
, p. 209 - 212 (2007/10/03)
N-Heterocyclic carbenes (NHC) are efficient catalysts for transesterification/acylation reactions involving secondary alcohols. The catalytic transformations are carried out employing low catalyst loadings in convenient reaction times at room temperature.
Concerted Bimolecular Substitution Reactions of 1-Phenylethyl Derivatives
Richard, John P.,Jencks, William P.
, p. 1383 - 1396 (2007/10/02)
Substituted 1-phenylethyl derivatives with ?+ > -0.08 exhibit bimolecular substitution reactions with azide ion in 20percent acetonitrile in water.The reactions with 1-phenylethyl chlorides follow a Hammett correlation with ρ = -2.9, compared with ρ = -5.6 (r+ = 1.15) for solvolysis.Swain-Scott correlations give values of s = 0.46 and 0.22 for 1-(4-nitrophenyl)ethyl chloride and tosylate, respectively; there are large positive deviations for azide ion and water and negative deviations for cyanide ion.The value of βnuc is 0.09 for reactions of substituted acetates with the chloride.The reactions exhibit ''synergism'' between the nucleophile and leaving group that favors the bimolecular reaction with Me2S, Br- > Cl- > OTs- leaving groups.The bimolecular reaction with azide follows the Grunwald-Winstein Y correlation with m = 0.8 in methanol-water mixtures.Bimolecular reactions with less reactive nucleophiles in the series N3-, CN-, AcO-, and ROH appear at progressively larger ? values, as the carbocation becomes less stable.It is concluded that these reactions are SN2 displacements that proceed through an open, ''exploded'' transition state that closely resembles a carbocation.Specific salt effects are small in water but are significant in acetonitrile-water mixtures and could be mistaken for normal or induced common ion rate depressions.No evidence was obtained for nucleophilic assistance to the formation of a carbocation intermediate.Concurrent SN1 and SN2 pathways occur in the reactions with solvent and azide of dimethylsulfonium ion, 1-(4-fluorophenyl)ethyl chloride, 1-(3-methoxyphenyl)ethyl chloride, and, probably, 1-(3-nitro-4-methoxyphenyl)ethyl chloride.Crude estimates of the lifetime of the carbocation intermediate in the presence of the nucleophile are consistent with the hypothesis that the concerted reactions are enforced by the absence of a significant lifetime of the carbocation in the presence of the nucleophile and that stepwise mechanisms are followed when the intermediate has a significant lifetime; the change from a stepwise to a concerted mechanism occurs when the intermediate ceases to have a lifetime in the presence of a nucleophile.
Reactions of Substituted 1-Phenylethyl Carbocations with Alcohols and Other Nucleophilic Reagents
Richard, John P.,Jencks, William P.
, p. 1373 - 1383 (2007/10/02)
Selectivities of a series of substituted 1-phenylethyl carbocations toward alcohols and other nucleophiles have been determined by product analysis.The 1-(4-dimethylamino)phenyl)ethyl carbocation exhibits a high selectivity in its reactions with alcohols , with KEtOH/KTFE = 140 and βnuc = 0.5.The selectivity for activation-limited reactions with alcohols decreases progressively with increasing reactivity of the carbocation, in contrast to the behavior expected from the N+ scale of reactivity.A sharper drop in selectivity for carbocations that react faster than ca. 109 S-1 is attributed to an approach to limiting rate constants for the more reactive alcohol.The limiting selectivity of kEtOH/kTFE = 2 for carbocations with ks ca. 1011 S-1 may represent reaction from a pool of solvent molecules in which there is a modest charge-dipole interaction between the alcohol and carbocation.The relatively low reactivity of water corresponds to that expected for an alcohol of pKa ca. 13.This is ascribed to an imbalance between charge development and solvation of the transition state compared with H3O+.Substituted acetate anions react with the 1-(4-methoxyphenyl)ethyl carbocation with βnuc = 0.13.The selectivity decreases with increasing cation reactivity as the carboxylate ions approach limiting rate constants of ca. 5 * 108 M-1 s-1.This relatively low limit is attributed to a requirement for desolvation of basic oxygen anions before reaction.A dependence of solvent selectivity on the leaving group shows that the 1-(4-methylphenyl)ethyl carbocation reacts with solvent, in part, through an ion pair.Azide ion reacts from a pool that can be described by an equilibrium constant of Kas = 0.3 M-1.Styrene formation from this carbocation is catalyzed by a leaving carboxylate ion and by added buffers, wih β = 0.14.The equilibrium constant for the formation of a reactive base-cation pair is ca. 0.04 M-1.Rate constants for collapse of the ion pair, to form ester, and for proton removal, to form 4-methylstyrene, were estimated to be approximately 1.6 * 1010 s-1 and 6 * 107 s-1, respectively.The rate constants for deprotonation and for hydration of the styrene give the acid dissociation constant of the carbocation to form 4-methylstyrene, pKA = -11.2.
