The activation of C-H bonds has revolutionized modern synthetic chemistry. However, no general strategy for enantiospecific C-H activation has been developed to date. We herein report an enantiospecific C-H activation reaction followed by deuterium incorporation at stereogenic centers. Mechanistic studies suggest that the selectivity for the α-position of the directing heteroatom results from a four-membered dimetallacycle as the key intermediate. This work paves the way to novel molecular chemistry on nanoparticles.
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http://dx.doi.org/10.1002/anie.201504554 | DOI Listing |
Science
December 2024
Department of Chemistry, Scripps Research, 10550 North Torrey Pines Road, La Jolla, CA, USA.
Modern medicinal chemists are targeting more complex molecules to address challenging biological targets, which leads to synthesizing structures with higher sp character (Fsp) to enhance specificity as well as physiochemical properties. Although traditional flat, high-fraction sp molecules, such as pyridine, can be decorated through electrophilic aromatic substitution and palladium (Pd)-based cross-couplings, general strategies to derivatize three-dimensional (3D) saturated molecules are far less developed. In this work, we present an approach for the rapid, modular, enantiospecific, and diastereoselective functionalization of piperidine (saturated analog of pyridine), combining robust biocatalytic carbon-hydrogen oxidation with radical cross-coupling.
View Article and Find Full Text PDFJ Am Chem Soc
December 2024
Laboratory of Asymmetric Catalysis and Synthesis, Institute of Chemical Sciences and Engineering, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne 1015, Switzerland.
Chiral cyclopentadienyl (Cp) metal complexes are frequently used in asymmetric catalysis by virtue of their high reactivity and selectivity. Planar-chiral-only rhodium and iridium cyclopentadienyl complexes are particularly promising due to unrestricted chemical space for Cp ligand design while retaining structural simplicity. However, they are currently still niche because of a lack of efficient synthetic strategies that avoid lengthy chiral auxiliary routes or chiral preparatory HPLC resolution of the complexes.
View Article and Find Full Text PDFChem Sci
December 2024
Key Laboratory for Advanced Material, Joint International Research Laboratory of Precision Chemistry and Molecular Engineering, Feringa Nobel Prize Scientist Joint Research Center, Shanghai Key Laboratory of Functional Materials Chemistry, Institute of Fine Chemicals, Frontiers Science Center for Materiobiology and Dynamic Chemistry, School of Chemistry and Molecular Engineering, East China University of Science & Technology Shanghai 200237 China
Org Lett
May 2024
Department of Chemistry, McGill University. 801 Sherbrooke St. West, Montréal, Québec H3A 0B8, Canada.
Solvent-switchable and site-selective phosphorylation of imidazoles at the C2 or C5 position of the imidazole ring was achieved via 1,4-palladium migration. -Chiral -butyl(aryl)phosphine oxides were cross-coupled to 1-(2-bromophenyl)-1-imidazoles with high enantiospecificity, thereby leading to a novel class of chiral imidazole-based phosphine oxides. As proof of concept, reduction of an analogue yielded the corresponding -chiral 2-phosphinyl imidazole ligand, which was shown to induce high enantioselectivity in the formation of axially chiral molecules synthesized via Pd-catalyzed Suzuki-Miyaura cross-coupling.
View Article and Find Full Text PDFNat Synth
July 2022
Department of Chemistry, Merkert Chemistry Center, Boston College, Chestnut Hill, MA, USA.
Chiral amines are among the most important organic compounds and have widespread applications. Enantioselective construction of chiral amines is a major aim in organic synthesis. Among synthetic methods, direct functionalization of omnipresent C-H bonds with common organic nitrogen compounds represents one of the most attractive strategies.
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