Abstract:The enantioselective redox annulation of nitroalkynes with indoles is enabled by gold/chiral phosphoric acid dual catalysis.Arange of indolin-3-one derivatives bearing quaternary stereocenters at the C2 position were afforded in good yields and excellent enantioselectivities (up to 96 %ee) from readily available starting materials.
“…3 ). It is worth mentioning that enantioselective catalytic reactions based on such unactivated achiral ketonitrones to create tetrasubstituted carbon stereocenters is unprecedented 65 , although two protocols using activated ketonitrones have been reported 66 , 67 . Fig.…”
Optically active spirocyclic compounds play an important role in drug discovery, and new synthetic strategies for the efficient generation of spiro stereocenters are in much demand. Here we report a catalytic enantioselective cycloaddition using spirocyclic donor–acceptor cyclopropanes as a promising approach for the generation of spiro stereocenters. A diastereo- and enantioselective [3 + 3] cycloaddition of spirocyclopropyl oxindoles with both aldonitrones and ketonitrones is developed. The key to reaction development is the activation of spirocyclopropyl oxindoles by a suitable electron-withdrawing N-protecting group. This activation approach offers the promise of a general solution to enable spirocyclopropyl oxindoles as synthons for catalytic enantioselective synthesis of spirocyclic oxindoles featuring a C3 spiro stereocenter, a prominent structural motif in drugs and pharmaceutically active compounds. This protocol also constitutes the catalytic enantioselective reaction using unactivated achiral ketonitrones to construct tetrasubstituted carbon stereocenters.
“…3 ). It is worth mentioning that enantioselective catalytic reactions based on such unactivated achiral ketonitrones to create tetrasubstituted carbon stereocenters is unprecedented 65 , although two protocols using activated ketonitrones have been reported 66 , 67 . Fig.…”
Optically active spirocyclic compounds play an important role in drug discovery, and new synthetic strategies for the efficient generation of spiro stereocenters are in much demand. Here we report a catalytic enantioselective cycloaddition using spirocyclic donor–acceptor cyclopropanes as a promising approach for the generation of spiro stereocenters. A diastereo- and enantioselective [3 + 3] cycloaddition of spirocyclopropyl oxindoles with both aldonitrones and ketonitrones is developed. The key to reaction development is the activation of spirocyclopropyl oxindoles by a suitable electron-withdrawing N-protecting group. This activation approach offers the promise of a general solution to enable spirocyclopropyl oxindoles as synthons for catalytic enantioselective synthesis of spirocyclic oxindoles featuring a C3 spiro stereocenter, a prominent structural motif in drugs and pharmaceutically active compounds. This protocol also constitutes the catalytic enantioselective reaction using unactivated achiral ketonitrones to construct tetrasubstituted carbon stereocenters.
“…Notably, this is the rst method to use the inactivated ketonitrones in enantioselective catalytic synthesis; however, this eld has not received much attention. [78][79][80][81][82][83] It is common practice to modify the pharmaceutical properties of organic molecules by selectively adding a uoroalkyl group. Consequently, oxindoles with a uoroalkyl group at the C-3 position make intriguing targets for the creation of pharmaceuticals and biological probes.…”
Section: Chemical Reactivity Of 2-oxindole and Related Derivatives In...mentioning
confidence: 99%
“…Notably, this is the first method to use the inactivated ketonitrones in enantioselective catalytic synthesis; however, this field has not received much attention. 78–83…”
Section: Chemical Reactivity Of 2-oxindole and Related Derivatives In...mentioning
“…In this context, the introduction of bulky and extended substituents to the chiral ligands (biaryl bisphosphines, [ 20‐28 ] monodentate phosphoramidite, [ 29‐36 ] etc .) and tightly associated chiral counteranions (mainly chiral phosphoric acid [ 37‐44 ] ) embracing the gold active center and its active reaction site have been developed as one of practical and widely accepted strategies. [ 45‐50 ] The major drawback for this steric effect strategy is bringing much extra efforts to modify and prepare the chiral ligands and makes them even more expensive than the noble metal.…”
Section: Background and Originality Contentmentioning
A highly enantioselective gold-catalyzed intermolecular [3+2] cycloaddition of N-allenamides with nitrones was realized by the application of Ming-Phos M6 as a chiral ligand. Both enantiomers of the cycloadducts with opposite configuration could be obtained in high yields with high regio-and enantioselectivity by the employment of either diastereomer of the chiral ligand. The acidic N-H bond (hydrogen bonding) of sulfinamide moiety of Ming-Phos and pentaflurophenyl substituent (fluorine effect) may play important roles in enhancement of enantioselectivity, that is, Ming-Phos is a multifunctional ligand in this transformation.
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