A straightforward synthetic route to enantiopure spiro[indole-3,3'-indolizidines] is reported. The key step is a Lewis acid promoted cyclization of a Na-tosyltryptophanol-derived oxazolopiperidone lactam in the presence of Et3SiH.
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http://dx.doi.org/10.1021/ol0712327 | DOI Listing |
Org Lett
January 2025
Department of Chemistry, School of Science, China Pharmaceutical University, Nanjing 211198, People's Republic of China.
The development and enantioselective synthesis of two types of -symmetric spirobi[dihydrophenalene] structures is reported. The reaction proceeds via rhodium-catalyzed 2-fold asymmetric conjugate arylation of dienones followed by BF·OEt-promoted spirocyclization to give the enantiopure spiro products. Additive-dependent chemodivergent synthesis of 3,3'-diarylated 2,2',3,3'-tetrahydro-1,1'-spirobi[phenalene]-9,9'-diols (3,3'-Ar-SPHENOLs) and the corresponding spiro diary ethers from the same intermediate is achieved.
View Article and Find Full Text PDFOrg Lett
January 2025
Department of Chemistry, Indian Institute of Technology Guwahati, North Guwahati, Assam 781039, India.
Herein, an organocatalytic asymmetric desymmetrizing [4+2] cycloaddition/base-mediated oxidative aromatization reaction sequence has been developed between spirophthalide 2,5-cyclohexadienones and β-methyl cinnamaldehydes. The reaction proceeds through chiral dienamine intermediate formation, and the densely functionalized spirocyclic isobenzofuranone-embedded chiral arenes were formed in high yields with excellent enantioselectivities. A 2-fold desymmetrization reaction was also performed, and the products were obtained in high enantioselectivities.
View Article and Find Full Text PDFChemistry
December 2024
Department of Chemistry, Indian Institute of Technology Kanpur, Uttar Pradesh, Kanpur, 208016, India.
Herein, we report a copper-catalyzed enantioselective formal (3+3) and (3+2) cycloaddition reaction of isatin-derived tertiary propargylic esters with N,N-dimethylbarbituric acid and 4-hydroxycoumarins, respectively. In this process, the tertiary propargylic ester serves as both C3- and C2-synthons, facilitating the synthesis of optically active spirooxindole-pyran and furan scaffolds featuring an all-carbon quaternary stereocenter. The reaction delivers these spirocyclic frameworks in good yields with high enantioselectivities.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
December 2024
Hubei Research Center of Fundamental Science-Chemistry, College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, 430072, China.
The "Magic Methyl" effect has received tremendous interest in medicinal chemistry due to the significant pharmacological and physical modification of properties that have been observed upon introducing a methyl group, especially, a stereogenic methyl group into potential chiral drug candidates. The prevalence of stereogenic β-methyl ketone structural motifs in bioactive compounds and natural products has long motivated the development of enantioselective strategies toward their synthesis. Herein, we have rationally designed a Rh-catalyzed asymmetric monohydrogenation of readily-available β'-methylene conjugated enones with high efficiency and remarkable site-selectivity and enantioselectivity control for the practical construction of enantioenriched β'-methyl unsaturated enones that are difficult to access by other methods.
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December 2024
School of Physical Science and Technology, ShanghaiTech University, Shanghai 201210 China.
Imidazo[1,2-]pyridines are privileged heterocycles with diverse applications in medicinal chemistry; however, the catalytic asymmetric synthesis of these heterocyclic structures remains underexplored. Herein, we present an efficient and modular approach for the atroposelective synthesis of axially chiral imidazo[1,2-]pyridines via an asymmetric multicomponent reaction. By utilizing a chiral phosphoric acid catalyst, the Groebke-Blackburn-Bienaymé reaction involving various 6-aryl-2-aminopyridines, aldehydes, and isocyanides gave access to a wide range of imidazo[1,2-]pyridine atropoisomers with high to excellent yields and enantioselectivities.
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