Chiral aliphatic amine and alcohol derivatives are ubiquitous in pharmaceuticals, pesticides, natural products and fine chemicals, yet difficult to access due to the challenge to differentiate between the spatially and electronically similar alkyl groups. Herein, we report a nickel-catalyzed enantioselective hydroalkylation of acyl enamines and enol esters with alkyl halides to afford enantioenriched α-branched aliphatic acyl amines and esters in good yields with excellent levels of enantioselectivity. The operationally simple protocol provides a straightforward access to chiral secondary alkyl-substituted amine and secondary alkyl-substituted alcohol derivatives from simple starting materials with great functional group tolerance.
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http://dx.doi.org/10.1038/s41467-021-22983-7 | DOI Listing |
Angew Chem Int Ed Engl
January 2025
Dalian University of Technology, School of Chemical Engineering, No 2 Linggong Road,Ganjingzi District, 116024, Dalian, CHINA.
The Pd-catalyzed asymmetric hydrogenolysis rearrangement of allylic acetates using (s-Bu)3BHK has been described, achieving the synthesis of axially chiral alkylidene cycloalkanes with excellent enantioselectivities (up to 99% ee) and a wide substrate scope (30 examples of cyclohexanes and cyclobutanes). To the best of our knowledge, this is the first time to achieve synthesis of axially chiral olefins via asymmetric hydrogenolysis of allylic acetates. This methodology not only offers a novel synthetic pathway for non-atropisomeric axially chiral structures but also highlights the potential of asymmetric hydrogenolysis as a powerful tool in synthetic organic chemistry.
View Article and Find Full Text PDFOrg Lett
January 2025
Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry, Chemical Engineering and Materials Science & Collaborative Innovation Center of Suzhou Nano Science and Technology, Soochow University, Suzhou 215123, P. R. China.
The azahelicenes are structurally fascinating and practically useful chiral scaffolds, but their synthesis, especially in a catalytically asymmetric manner, is rather challenging. Herein, we report a CPA-catalyzed transfer hydrogenation process, which enables a rapid kinetic resolution of aza[6]helicenes. The established strategy provides facile access to enantioenriched aza[6]helicenes and tetrahydro[6]helicenes from easily available starting materials.
View Article and Find Full Text PDFACS Catal
January 2025
Department of Biotechnology, Delft University of Technology, van der Maasweg 9, 2629 HZ Delft, The Netherlands.
Reductive amination is one of the most synthetically direct routes to access chiral amines. Several Imine Reductases (IREDs) have been discovered to catalyze reductive amination (Reductive Aminases or RedAms), yet they are dependent on the expensive phosphorylated nicotinamide adenine dinucleotide cofactor NADPH and usually more active at basic pH. Here, we describe the discovery and synthetic potential of an IRED from (RedAm) that catalyzes reductive amination between a series of medium to large carbonyl and amine compounds with conversions of up to >99% and 99% enantiomeric excess at neutral pH.
View Article and Find Full Text PDFRSC Chem Biol
December 2024
Department of Chemistry, Texas A&M University College Station Texas 77843 USA
Despite the growing interest in mirror-image l-oligonucleotides, both as a robust nucleic acid analogue and as an artificial genetic polymer, their broader adoption in biochemical research and medicine remains hindered by challenges associated with the synthesis of long sequences, especially for l-RNA. Herein, we present a novel strategy for assembling long l-RNAs the joining of two or more shorter fragments using cross-chiral ligase ribozymes together with new substrate activation chemistry. We show that 5'-monophosphorylated l-RNA, which is readily prepared by solid-phase synthesis, can be activated by chemical attachment of a 5'-adenosine monophosphate (AMP) or diphosphate (ADP), yielding 5'-adenosyl(di- or tri-)phosphate l-RNA.
View Article and Find Full Text PDFNat Chem
January 2025
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA.
Atomically precise nanoclusters can be assembled into ordered superlattices with unique electronic, magnetic, optical and catalytic properties. The co-crystallization of nanoclusters with functional organic molecules provides opportunities to access an even wider range of structures and properties, but can be challenging to control synthetically. Here we introduce a supramolecular approach to direct the assembly of atomically precise silver nanoclusters into a series of nanocluster‒organic ionic co-crystals with tunable structures and properties.
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