Chemoenzymatic dynamic kinetic resolution (DKR) of amines involving sulfanyl radical-induced racemization happened to be the very first switchable DKR process allowing the synthesis of either (R)- or (S)-amides, in good yield and high enantiomeric excess, depending on the nature of the enzyme; the different steps of the development of (S)-selective DKR are discussed.
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http://dx.doi.org/10.1039/c0ob00054j | DOI Listing |
J Org Chem
December 2024
Medicines for All Institute, Virginia Commonwealth University, Richmond, Virginia 23284-3068, United States.
Herein, we describe a new seven-step approach to prepare ()-1-(3,6-dibromopyridin-2-yl)-2-(3,5-difluorophenyl)ethan-1-amine (()-) from the inexpensive 2-(3,5-difluorophenyl)acetic acid. The key steps in the sequence include (1) the Weinreb amide-based ketone synthesis to provide an entry point to the core structure; (2) simple functional group transformations to afford the racemic amine -; and (3) dynamic kinetic resolution (DKR) to access the chiral amine ()-. This seven-step process delivered the enantiopure amine ()- in an overall isolated yield of approximately 15%.
View Article and Find Full Text PDFNat Commun
August 2024
College of Pharmaceutical Science & Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou, P. R. China.
N-oxides play a pivotal role in natural products and emerging drug design, while also serving as valuable ligand scaffolds in organometallic chemistry. Among heteroatom oxidations, the conversion of amines to N-oxides is a critical and challenging facet. We present here a highly enantioselective N-oxidation methodology for both cyclic and acyclic amines.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
September 2024
Instituto Investigaciones Químicas (CSIC-US), Centro de Innovación en Química Avanzada (ORFEO-CINQA), C/ Américo Vespucio 49, 41092, Sevilla, Spain.
A ruthenium-catalyzed reductive amination via asymmetric transfer hydrogenation (ATH) has been used to perform an efficient dynamic kinetic resolution (DKR) of N-aryl 2-formyl pyrroles decorated with a phosphine moiety positioned at the ortho' position. The strategy relies on the labilization of the stereogenic axis in the substrate facilitated by a transient Lewis acid-base interaction (LABI) between the carbonyl carbon and the phosphorus center. The reaction features broad substrate scope of aliphatic amines and N-aryl pyrrole scaffolds, and proceeds under very mild conditions to afford P,N atropisomers in good to high yields and excellent enantioselectivities (up to 99 % ee) for both diphenyl and dicyclohexylphosphino derivatives.
View Article and Find Full Text PDFChembiochem
August 2024
Institute of Chemistry, Biocatalytic Synthesis Group, Otto von Guericke University of Magdeburg, Building 28, Universitätsplatz 2, 39106, Magdeburg, Germany.
This study explores a combination of the concept of enantioselective enzymatic synthesis of β-chiral amines through transamination with in situ product crystallization (ISPC) to overcome product inhibition. Using 2-phenylpropanal as a readily available and easily racemizing substrate of choice, (R)-β-methylphenethylamine ((R)-2-phenylpropan-1-amine) concentrations of up to 250 mM and enantiomeric excesses of up to 99 % are achieved when using a commercially available transaminase from Ruegeria pomeroyi in a fed-batch based dynamic kinetic resolution reaction on preparative scale. The source of substrate decomposition during the reaction is also investigated and the resulting unwanted byproduct formation is successfully reduced to insignificant levels.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
April 2024
College of Chemistry, Huazhong Agricultural University, Wuhan, 430070, P. R. China.
Bio-catalysis represents a highly efficient and stereoselective method for the synthesis of valuable chiral compounds, however, the poor stability and limited reaction types of free enzymes restrict their wide application in industrial production. In this work, to overcome these problems, a multifunctional photoenzymatic nanoreactor CALB@COF-Ir was developed through the encapsulation of Candida antarctica lipase B (CALB) in a photosensitive covalent organic framework COF-Ir. This bio-nanocluster serves as efficient catalysts in asymmetric dynamic kinetic resolution (DKR) of secondary amines to give a series of chiral amines in high yields (up to 99 %) and enantioselectivities (up to 99 % ee).
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