Owing to the more abundant occurrence of racemic compounds compared to prochiral or meso forms, most enantiomerically pure products are obtained via racemate resolution. This review summarizes (chemo)enzymatic enantioconvergent processes based on the use of hydrolytic enzymes, which are able to invert a stereocenter during catalysis that can overcome the 50%-yield limitation of kinetic resolution. Recent developments are presented in the fields of inverting or retaining sulfatases, epoxide hydrolases and dehalogenases, which allow the production of secondary alcohols or vicinal diols at a 100% theoretical yield from a racemate via enantioconvergent processes.
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http://dx.doi.org/10.1016/j.tibtech.2013.05.005 | DOI Listing |
J Am Chem Soc
December 2024
Hefei National Laboratory for Physical Sciences at the Microscale and Department of Chemistry, University of Science and Technology of China, Hefei, 230026, China.
Asymmetric catalytic versions of electricity-driven processes hold immense potential for the sustainable preparation of chiral compounds. However, the involvement of anodic oxidative cross-dehydrogenative coupling events between two distinct nucleophiles makes it challenging for a chiral catalyst to regulate the stereochemistry of the products. Our current electrocatalytic strategy for enantioconvergent cross-dehydrogenative α- and γ-nitroalkylation via radical-based pathways produces an array of enantioenriched nitroesters without supplementary stoichiometric oxidants.
View Article and Find Full Text PDFOrg Lett
October 2024
Jiangsu Key Laboratory of Neuropsychiatric Diseases and Department of Medicinal Chemistry, College of Pharmaceutical Sciences, Soochow University, 199 Ren-Ai Road, Suzhou, Jiangsu 215123, China.
Cobalt-catalyzed enantioconvergent cross-coupling of C(sp)-H bonds with -generated sulfenate anions is achieved to access chiral sulfoxides, which are found in the structures of many biologically active agents. The more challenging aliphatic C-H bonds as well as sterically hindered substrates containing tertiary C-H bonds could also be tolerated well. Mechanistic studies indicate that the transformation could undergo a CoS(O)R-mediated single-electron transfer with -fluorocarboxamides, followed by a 1,5-hydrogen atom transfer and then a pivotal organocobalt(IV)-controlled enantioselective cross-coupling process.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
December 2024
Joint School of National University of Singapore and Tianjin University, International Campus of Tianjin University, Binhai New City, 350207, Fuzhou, China.
We present herein a catalytic enantioconvergent diamination of racemic allylic alcohols with the construction of two C-N bonds and 1,3-nonadjacent stereocenters. This iridium/chiral phosphoric acid cooperative catalytic system operates through an atom-economical borrowing hydrogen amination/aza-Michael cascade, and converts readily available phenylenediamines and racemic allylic alcohols to 1,5-tetrahydrobenzodiazepines in high enantioselectivity. An intriguing solvent-dependent switch of diastereoselectivity was also observed.
View Article and Find Full Text PDFNat Chem
December 2024
Department of Chemistry and Biochemistry, University of California, Santa Barbara, CA, USA.
Catalytic asymmetric dearomatization represents a powerful means to convert flat aromatic compounds into stereochemically well-defined three-dimensional molecular scaffolds. Using new-to-nature metalloredox biocatalysis, we describe an enzymatic strategy for catalytic asymmetric dearomatization via a challenging radical mechanism that has eluded small-molecule catalysts. Enabled by directed evolution, new-to-nature radical dearomatases P450-P450 facilitated asymmetric dearomatization of a broad spectrum of aromatic substrates, including indoles, pyrroles and phenols, allowing both enantioconvergent and enantiodivergent radical dearomatization reactions to be accomplished with excellent enzymatic control.
View Article and Find Full Text PDFChem Sci
August 2024
Frontiers Science Center for Flexible Electronics (FSCFE), Shaanxi Institute of Flexible Electronics (SIFE), Shaanxi Institute of Biomedical Materials and Engineering (SIBME), Northwestern Polytechnical University (NPU) 127 West Youyi Road Xi'an 710072 China
An efficient and highly enantioconvergent and diastereoselective ternary catalysis in a one-pot process is reported, which represents an integrated strategy for the synthesis of atropisomeric hydrazides with defined vicinal central and axial chirality from readily available racemic α-amino-ynones, azodicarboxylates, and Morita-Baylis-Hillman (MBH) carbonates. This method utilizes -generated racemic pyrrolin-4-ones hydroamination of racemic α-amino-ynones by AuCl catalysis as a novel and versatile C1 synthon, which engage commercially available azodicarboxylates to generate amination products in high yields and uniformly excellent enantioselectivities under the catalysis of a chiral phosphoric acid. Following amination, -alkylation catalyzed by diastereoselective organocatalyst afforded axially chiral hydrazides with excellent diastereoselectivities (>98 : 2 dr).
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