The asymmetric synthesis of tricyclic compounds by the desymmetrization of cyclohexadienones is presented. The reaction tolerated a large variety of substituents at different positions of the cyclohexadienone, and heterocyclic rings of different sizes were accessible. Density functional theory calculations showed that the reaction proceeds through an asynchronous [4+2] cycloaddition.
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http://dx.doi.org/10.1002/anie.201402853 | DOI Listing |
Org 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 PDFChem Commun (Camb)
January 2025
Department of Chemistry, Indian Institute of Technology Jammu, Jagti, NH-44, Nagrota Bypass, Jammu 181221, J&K, India.
A highly regio-, enantio- and diastereo-selective strategy involving initial enantioselective conjugate addition to 4-nitro-5-styrylisoxazoles serves as a key step for the desymmetrization of 2,5-cyclohexadienones has been disclosed. We have designed a new class of 2,5-cyclohexadienones appended with 4-nitro-5-styrylisoxazoles to undergo organocatalytic asymmetric double or triple conjugate addition in a domino sequence depending on the substrate type leading to desymmetrization of the 2,5-cyclohexadienone core. The developed protocol allows the construction of a valuable hydrophenanthrene core or a unique bridged scaffold bearing multiple chiral centers with excellent enantio- (up to >99.
View Article and Find Full Text PDFOrg Lett
December 2024
Process Research & Development, MRL, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
We report the remote stereocontrol of all-carbon quaternary γ-centers via an ene-reductase (ERED)-catalyzed desymmetrization of prochiral cyclohexadienones. By leveraging high-throughput experimentation (HTE) protocols, we were able to rapidly identify EREDs capable of desymmetrizing both spirocyclic cyclohexadienones and non-spirocyclic 2,6-disubstituted cyclohexadienone substrates in up to 85% yield with excellent levels of stereoselectivity (up to >99% ee and >20:1 dr) under mild reaction conditions.
View Article and Find Full Text PDFNat Commun
November 2024
Engineering Research Center of Sichuan-Tibet Traditional Medicinal Plant, College of Chemistry and Chemical Engineering, Chengdu University, Chengdu, China.
Carbon-silicon-switch strategy, replacing one specific carbon atom in organic molecules with a silicon, has garnered significant interest for developing new functional molecules. However, the influence of a reaction regarding its selectivity and reactivity by carbon-silicon-switch strategy has far less been investigated. Here we discover an unusual carbon-silicon-switch effect in the enantioselective construction of silicon-stereogenic center.
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October 2024
Department of Chemistry, Indian Institute of Science Education and Research (IISER) Bhopal, Bhopal By-pass Road, Bhauri, Bhopal-462066, India.
Enantioselective desymmetric spirocyclization is a powerful tool for concisely generating intricate 3D molecular architectures from readily accessible substrates. Herein, we report an organocatalytic desymmetric spirocyclization of enone-tethered 2,5-cyclohexadienone with 3-arylisoxazol-5(4)-one to access enantioenriched spiro-fused scaffolds featuring four consecutive stereogenic centers in high yields and excellent diastereo- and enantioselectivities. This protocol could proceed smoothly under parts per million-level organocatalyst loading.
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