Asymmetric Synthesis of Spiro[3,2'-morpholine-oxindoles] Derivatives via the [5 + 1] Annulation Reaction.

An efficacious method in which BINOL-type chiral imidodiphosphoric acid catalyzed the asymmetric [5 + 1] annulation reaction of 2-pyrrolylphenol with 1-methylindoline-2,3-dione was established. The strategy tolerated a broad substrate scope, and 30 examples were obtained. A range of enantioenriched spiro[3,2'-morpholine-oxindole] derivatives which incorporate a tertiary stereocenter, with moderate to excellent yields (up to 96%) and enantioselectivities (up to 99%) under mild conditions, was delivered.

Enantioselective Domino Reaction of 3-Vinylindole and -Quinone Methides Enabled by Chiral Imidodiphosphoric Acids: Asymmetric Synthesis of Multisubstituted 3-Indolyl Cyclopenta[]indoles.

The development of a stereoselective method for the rapid assembly of structurally complex molecules remains fascinating and challenging in synthetic organic chemistry. Here, we report an enantioselective domino reaction between 3-vinylindole and -quinone methide for the preparation of 3-indolyl cyclopenta[]indoles containing multiple chiral centers. Chiral imidodiphosphoric acids enable this cascade asymmetric process, delivering a series of products with excellent yields (≤99%), enantioselectivities (≤99%), and diastereoselectivities (≤20:1 dr).

Asymmetric syntheses of spiro[benzofuro-cyclopenta[1,2-b]indole-indoline] scaffolds via consecutive cyclization.

An efficient method to construct enantioenriched spiro[benzofuro-cyclopenta[1,2-b]indole-indoline] scaffolds via consecutive cyclization is described here. The new scaffolds possess five successive chiral stereogenic centers and two spiroheterocycles. A range of highly enantioenriched scaffolds has been obtained with up to 93% yield, 99% ee and >19 : 1 d.

Asymmetric Synthesis of 1,1,1-Triarylethanes by Chiral Imidodiphosphoric Acid Catalyzed Nucleophilic Addition of Pyrrole and Indoles to 3-Vinylindoles.

Chiral imidodiphosphoric acids were employed as efficient catalysts in the enantioselective addition reaction of pyrrole and indoles to 3-vinylindoles. A series of optically active 1,1,1-triarylethmanes bearing quaternary stereocenters were synthesized in excellent yields (up to 99% yield) and enantioselectivities (up to 98% ee). Gram-scale reactions of and as well as and demonstrated the synthetic utility of this methodology.

Chiral Imidodiphosphoric Acid-Catalyzed Highly Diastereo- and Enantioselective Synthesis of Poly-Substituted 3,4-Dihydro-2-pyrans: [4 + 2] Cycloadditions of β,γ-Unsaturated α-Ketoesters and 3-Vinylindoles.

Imidodiphosphoric acids were employed to catalyze inverse-electron-demand hetero-Diels-Alder reaction of β,γ-unsaturated α-ketoesters and 3-vinylindoles. A series of optically active 3,4-dihydro-2-pyran derivatives with three contiguous stereogenic centers was synthesized in excellent yields (70-99%), diastereoselectivities (>20:1), and enantioselectivities (73-99%). The resulting indole containing 3,4-dihydro-2-pyran could be converted to tetrahydropyran derivatives, which appear in several biological active compounds by simple hydrogenation reduction.

Organocatalyzed nucleophilic addition of pyrazoles to 2H-azirines: asymmetric synthesis of 3,3-disubstituted aziridines and kinetic resolution of racemic 2H-azirines.

The first organocatalytic asymmetric nucleophilic addition of arylpyrazoles to 2H-azirines and kinetic resolution of racemic 2H-azirines have been realized. Chiral aziridines were obtained with up to 98% yields and up to 99.9% ee.