Yi-Xia Jia

Dual Catalysis for the Redox Annulation of Nitroalkynes with Indoles: Enantioselective Construction of Indolin‐3‐ones Bearing Quaternary Stereocenters

The enantioselective redox annulation of nitroalkynes with indoles is enabled by gold/chiral phosphoric acid dual catalysis. A range 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.

Enantioselective Friedel–Crafts reaction of 4,7-dihydroindoles with β-CF3-β-disubstituted nitroalkenes

Using a Ni(ClO4)2–bisoxazoline complex as a catalyst, Friedel–Crafts alkylations of 4,7-dihydroindoles with β-CF3-β-disubstituted nitroalkenes were carried out with high enantioselectivities (up to 91%) to give alkylated dihydroindoles bearing trifluoromethylated all-carbon quaternary stereocenters in good yields. The corresponding chiral C2 alkylated indoles were obtained with complete preservation of enantiomeric purity by oxidation with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ).

Indolizine synthesis via Cu-catalyzed cyclization of 2-(2-enynyl)pyridines with nucleophiles

Efficient and atom-economical access to indolizines has been developed by a Cu-catalyzed cyclization of 2-(2-enynyl)pyridines with various nucleophiles through simultaneous formation of a C–N bond and a remote carbon–nucleophile bond. 1,3-Dicarbonyl compounds, indoles, amides, alcohol, and even water, were used as nucleophiles in this reaction. Good to excellent yields of the corresponding indolizines were obtained under mild reaction conditions.

Enantioselective Dearomative Difunctionalization of Indoles by Palladium‐Catalyzed Heck/Sonogashira Sequence

Palladium-catalyzed enantioselective dearomative arylalkynylation of N-substituted indoles, through a Heck/Sonogashira sequence, was established using a new BINOL-based phosphoramidite as the chiral ligand. A wide range of 2,3-disubstituted indolines, bearing vicinal quaternary and tertiary stereocenters, were efficiently constructed in one step with excellent enantioselectivities (up to 97 % ee) and diastereoselectivities (>20:1).

Palladium-catalyzed three-component cascade reaction: facial access to densely functionalized indolizines.

A palladium-catalyzed three-component cascade reaction of 2-(2-enynyl)pyridines with nucleophiles and allyl halides has been developed, enabling the synthesis of densely functionalized indolizines in moderate to good yields. The newly developed methodology offers several practical advantages, including operational simplicity, ready availability of starting materials, and mild reaction conditions.

Palladium-catalyzed dearomative arylalkynylation of indoles.

A palladium-catalyzed indole dearomative bisfunctionalization via a domino arylation/alkynylation sequence has been developed, which provides a reliable approach to a series of structurally diverse tetracyclic indolines bearing vicinal tertiary and quaternary stereocenters in moderate to good yields and excellent diastereoselectivities.

Enantioselective Friedel–Crafts C2-alkylation of 3-substituted indoles with trifluoropyruvates and cyclic N-sulfonyl α-ketiminoesters

Enantioselective Friedel–Crafts C2-alkylation reactions of 3-substituted indoles with trifluoropyruvates and cyclic N-sulfonyl α-ketiminoesters were developed by using the complexes of Cu(OTf)2 or Zn(OTf)2 with chiral bisoxazoline ligands. A range of chiral indole-containing trifluoromethylated α-hydroxyesters and cyclic α-aminoesters bearing quaternary stereogenic centers were afforded in good yields and excellent enantioselectivities (up to 99% ee) under mild conditions.

Palladium-catalyzed asymmetric dearomative alkenylation of indoles through a reductive-Heck reaction

A highly enantioselective intramolecular dearomatizing olefination of indoles has been developed through a Pd-catalyzed reductive Heck reaction. This protocol provides efficient access to optically active tetracyclic indolines bearing C2-alkenylated quaternary stereocenters in good yields with excellent enantioselectivities.

Palladium-Catalyzed Enantioselective Intramolecular Dearomative Heck Reaction

Enantioselective intramolecular dearomative Heck reactions have been developed by Pd-catalyzed cross-coupling of aryl halides or aryl triflates with the internal C═C bond of indoles, benzofurans, pyrroles, and furans. A variety of structurally unique spiroheterocycles and benzofused heterocycles having N/O-substituted quaternary carbon stereocenters, and exocyclic olefin moieties were afforded in moderate to excellent yields with good to excellent enantioselectivities, showing a broad scope of the present protocol. A series of new BINOL- and H8-BINOL-based phosphoramidite ligands were synthesized and proved to be efficient chiral ligands in the reactions of C2-tethered substrates to form spiroheterocycles. ( S)-SEGPHOS turned out to be a good ligand for the reaction delivering benzofused indolines and pyrrolines. Synthetic applications based on transformations of the exocyclic double bonds were realized without loss of enantiopurities, including hydrogenation, hydroborylation, and stereospecific ring-expanding rearrangement.