5459-93-8Relevant articles and documents
A Lewis Base Nucleofugality Parameter, NFB, and Its Application in an Analysis of MIDA-Boronate Hydrolysis Kinetics
García-Domínguez, Andrés,Gonzalez, Jorge A.,Leach, Andrew G.,Lloyd-Jones, Guy C.,Nichol, Gary S.,Taylor, Nicholas P.
supporting information, (2022/01/04)
The kinetics of quinuclidine displacement of BH3 from a wide range of Lewis base borane adducts have been measured. Parameterization of these rates has enabled the development of a nucleofugality scale (NFB), shown to quantify and predict the leaving group ability of a range of other Lewis bases. Additivity observed across a number of series R′3-nRnX (X = P, N; R′ = aryl, alkyl) has allowed the formulation of related substituent parameters (nfPB, nfAB), providing a means of calculating NFB values for a range of Lewis bases that extends far beyond those experimentally derived. The utility of the nucleofugality parameter is explored by the correlation of the substituent parameter nfPB with the hydrolyses rates of a series of alkyl and aryl MIDA boronates under neutral conditions. This has allowed the identification of MIDA boronates with heteroatoms proximal to the reacting center, showing unusual kinetic lability or stability to hydrolysis.
Understanding the Role of Protic Ionic Liquids (PILs) in Reactive Systems: Rational Selection of PILs for the Design of Green Synthesis Strategies for Allylic Amines and β-Amino Esters
Bravo, María V.,Fernández, José L.,Adam, Claudia G.,Della Rosa, Claudia D.
, p. 919 - 926 (2019/07/31)
The reactive behaviour of protic ionic liquids (PILs) has been shown to be governed not only by their chemical structures but also by their global compositions, which include the presence of free acids and bases at equilibrium with ionic pairs. Six PILs composed of primary, secondary, or tertiary alkyl ammonium cations with two couterions, nitrate or acetate, were tested in model reactions with unsaturated substrates. The free species that were naturally present in these liquids were identified by cyclic voltammetry. Only tributylammonium nitrate was found to be mostly composed just of the ionic pair; the other five PILs also contain variable amounts of free acid and amine. In reactive systems, these free species determine the products of the reaction. In particular, allylic amines and β-amino esters were obtained in good yields (91 and 75 %, respectively) by reaction of conjugated dienes and acrylates in the presence of PILs. By taking into account the actual composition of each PIL, it was possible to direct the reaction path towards a specific product with good yields, to ensure acid catalysis, to avoid polymerization of the substrate, and to promote phase transfer of products. These results establish some useful guidelines for the rational design of new PIL-based one-step synthetic strategies.
Photometric Characterization of the Reductive Amination Scope of the Imine Reductases from Streptomyces tsukubaensis and Streptomyces ipomoeae
Matzel, Philipp,Krautschick, Lukas,H?hne, Matthias
, p. 2022 - 2027 (2017/10/07)
Imine reductases (IREDs) have emerged as promising enzymes for the asymmetric synthesis of secondary and tertiary amines starting from carbonyl substrates. Screening the substrate specificity of the reductive amination reaction is usually performed by time-consuming GC analytics. We found two highly active IREDs in our enzyme collection, IR-20 from Streptomyces tsukubaensis and IR-Sip from Streptomyces ipomoeae, that allowed a comprehensive substrate screening with a photometric NADPH assay. We screened 39 carbonyl substrates combined with 17 amines as nucleophiles. Activity data from 663 combinations provided a clear picture about substrate specificity and capabilities in the reductive amination of these enzymes. Besides aliphatic aldehydes, the IREDs accepted various cyclic (C4–C8) and acyclic ketones, preferentially with methylamine. IR-Sip also accepted a range of primary and secondary amines as nucleophiles. In biocatalytic reactions, IR-Sip converted (R)-3-methylcyclohexanone with dimethylamine or pyrrolidine with high diastereoselectivity (>94–96 % de). The nucleophile acceptor spectrum depended on the carbonyl substrate employed. The conversion of well-accepted substrates could also be detected if crude lysates were employed as the enzyme source.
