The first enantioselective Friedel-Crafts alkylation-acetalization-cascade of naphthols with α,β-unsaturated cyclic ketones and 1H-inden-1-ones was realized. 9-Amino(9-deoxy)epi-quinine A was the catalyst of choice for the realization of polycyclic structures with high enantiocontrol.
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http://dx.doi.org/10.1039/c2cc35582e | DOI Listing |
Molecules
January 2025
Department of Pharmacy, Jilin Medical University, Jilin 132013, China.
An efficient stereoselective synthesis of 10-hydroxy-10-(1-indol-3-yl)-9-(10)-phenanthrene derivatives was realized through an organocatalyzed Friedel-Crafts reaction of phenanthrenequinones and indoles using a (,)-dimethylaminocyclohexyl-squaramide as the catalyst. Under the optimized conditions, the desired chiral products were obtained in good yields (73-90%) with moderate to high ee values (up to 97% ee). Two pairs of synthesized enantiomers were subjected to evaluation of their antiproliferative activities on four types of human cancer cell lines and one human umbilical vein endothelial cell line using the CCK-8 assay.
View Article and Find Full Text PDFOrg Lett
December 2024
Institut für Chemie, Universität Oldenburg, D-26129 Oldenburg, Germany.
Optically active spirocycles were prepared in a sequence of two palladium-catalyzed reactions. In the first step, racemic α-(-iodophenyl)-β-oxo allyl esters were submitted to the palladium-catalyzed decarboxylative asymmetric allylic alkylation reaction, furnishing the α-allylated products with a quaternary stereocenter with good yields and enantioselectivities. Subsequently, these intermediate products were converted in a Heck reaction yielding the spirocyclic structures as a mixture of - and -cyclic regioisomers.
View Article and Find Full Text PDFChemistry
December 2024
Department of Chemistry, University of Kaiserslautern-Landau, Erwin-Schrödinger-Str. 54, 67663, Kaiserslautern, Germany.
A highly stereoselective Brønsted-acid catalyzed synthesis of densely substituted spiroisoindolinones from enamides and 3-hydroxy-isoindolinones is described. With simple Brønsted-acids, such as para-toluene sulfonic acid, spiroisoindolinones with three contiguous stereogenic centers are formed in high yields (up to 97 %) and diastereoselectivities (up to >98 : <2 : 0 : 0 dr) under mild reaction conditions. With the use of a chiral phosphoric acid catalyst, a diastereo- and enantioselective synthesis of the corresponding spiroisoindolinones was achieved.
View Article and Find Full Text PDFSci Adv
November 2024
Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China.
Despite the considerable potential applications for helically chiral molecules across various sectors, their catalytic asymmetric synthesis remains nascent and has seen very limited advancement compared to that of central and axial chiral compounds, primarily owing to the scarcity of available starting materials and the immense challenges associated with achieving stereochemical control. Herein, we report an innovative approach to the facile synthesis and catalytic kinetic resolution of uniquely structured and stereochemically complex helical polycyclic phenols by using a steric hindrance-regulated enantioselective dearomative amination reaction. The distinguished aspects of this method include the exceptional stability of the dearomatized products and impressive versatility of the recovered substrates in the construction of enantioenriched helical frameworks.
View Article and Find Full Text PDFJ Am Chem Soc
December 2024
Department of Chemistry, University of California, Berkeley, Berkeley, California 94720, United States.
In this report, we detail two distinct synthetic approaches to calyciphylline A-type alkaloids himalensine A and daphenylline, which are inspired by our analysis of the structural complexity of these compounds. Using MolComplex, a Python-based web application that we have developed, we quantified the structural complexity of all possible precursors resulting from one-bond retrosynthetic disconnections. This led to the identification of transannular bonds as especially simplifying to the molecular graph, and, based on this analysis, we pursued a total synthesis of himalensine A from macrocyclic intermediates with planned late-stage transannular ring formations.
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