The first enantioselective aza-Friedel-Crafts reaction between pyrroles and enamides has been achieved by using a novel H8-BINOL-type imidodiphosphoric acid catalyst. This methodology was also applied to the highly enantioselective aza-Friedel-Crafts reaction between pyrroles and imines. The catalyst loadings in these two reactions are low (0.3-2 mol%). Both processes are amenable to gram scales.
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http://dx.doi.org/10.1039/c5cc00685f | DOI Listing |
Chemistry
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 PDFJ Org Chem
November 2024
State Key Laboratory of NBC Protection for Civilian, Beijing 102205, China.
An efficient chiral phosphoric acid-catalyzed asymmetric aza Friedel-Crafts reaction of 3,4-dihydroisoquinolines and 1-naphthols is described. The reaction provides a general method for the synthesis of diverse chiral tetrahydroisoquinoline with 1-naphthol substituents at the C1-position in excellent yields and enantioselectivities. Based on the conducted mechanistic experiments, a plausible catalytic mechanism was proposed.
View Article and Find Full Text PDFOrg Lett
June 2024
Department of Chemistry, National Taiwan Normal University, Taipei, Taiwan 11677.
The first enantioselective vinylogous Mannich reaction is developed using 2-methoxyfuran under chiral spirophosphoric acid catalysis. The strategy involves 4-isoxazoline derivatives as cyclic ketimine surrogates and provides γ-butenolide scaffolds (up to 97% ee and >20:1 dr). The mechanistic investigations suggest that an generated water molecule plays a crucial role in delivering γ-butenolide, while the use of molecular sieves delivers -Friedel-Crafts products.
View Article and Find Full Text PDFOrg Lett
May 2024
State Key Laboratory of NBC Protection for Civilian, Beijing 102205, China.
The first catalytic enantioselective construction of chiral THIQUINOL and its derivatives has been accomplished through a chiral phosphoric-acid-catalyzed direct aza-Friedel-Crafts reaction of 3,4-dihydroisoquinolines with 2-naphthols/anthracen-2-ols/phenanthren-9-ol. This method offers a powerful and straightforward synthetic route toward chiral THIQUINOL derivatives with good to excellent yields and enantioselectivities. These structural motifs are crucial chiral components for further transformations into established or potential chiral ligands and catalysis.
View Article and Find Full Text PDFChemistry
May 2024
State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin, 300350, China.
New chiral ligands could be obtained by introducing proline moieties and imidazoline moieties to binaphthyl skeletons. The chiral ligands exhibited balanced rigidity and flexibility which could allow the change of the conformations during the reactions on one hand, and could provide sufficient asymmetric induction on the other. The proline moiety could act as a linker connecting the binaphthyl skeletons and the imidazoline moieties as well as a coordinating group for the central metal, and the electronic and steric properties of the imidazoline groups could be carefully fine-tuned by the use of different substituents.
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