Duo-Sheng Wang

Pd-Catalyzed Asymmetric Hydrogenation of Unprotected Indoles Activated by Brønsted Acids

The first highly enantioselective hydrogenation of simple indoles was developed with a Brønsted acid as an activator to form the iminium intermediate in situ, which was hydrogenated using Pd(OCOCF(3))(2)/(R)-H8-BINAP catalyst system with up to 96% ee. The present method provides an efficient route to enantioenriched 2-substituted and 2,3-disubstituted indolines.

Convergent Asymmetric Disproportionation Reactions: Metal/Brønsted Acid Relay Catalysis for Enantioselective Reduction of Quinoxalines

A convergent asymmetric disproportionation of dihydroquinoxalines for the synthesis of chiral tetrahydroquinoxalines using a metal/Brønsted acid relay catalysis system has been developed. The use of hydrogen gas as the reductant makes the convergent disproportionation an ideal atom-economical process. A dramatic reversal of enantioselectivity was observed in the reduction of quinoxalines because of the different steric demands in the 1,2- and 1,4-hydride transfer pathways.

Highly Enantioselective Iridium-Catalyzed Hydrogenation of 2-Benzylquinolines and 2-Functionalized and 2,3-Disubstituted Quinolines

The enantioselective hydrogenation of 2-benzylquinolines and 2-functionalized and 2,3-disubstituted quinolines was developed by using the [Ir(COD)Cl](2)/bisphosphine/I(2) system with up to 96% ee. Moreover, mechanistic studies revealed the hydrogenation mechanism of quinoline involves a 1,4-hydride addition, isomerization, and 1,2-hydride addition, and the catalytic active species may be a Ir(III) complex with chloride and iodide.

Biomimetic Asymmetric Hydrogenation: In Situ Regenerable Hantzsch Esters for Asymmetric Hydrogenation of Benzoxazinones

A catalytic amount of Hantzsch ester that could be regenerated in situ by Ru complexes under hydrogen gas has been employed in the biomimetic asymmetric hydrogenation of benzoxazinones with up to 99% ee in the presence of chiral phosphoric acid. The use of hydrogen gas as a reductant for the regeneration of Hantzsch esters makes this hydrogenation an ideal atom economic process.

Dehydration triggered asymmetric hydrogenation of 3-(α-hydroxyalkyl)indoles

Highly enantioselective hydrogenation of 3-(α-hydroxyalkyl)indoles promoted by a Bronsted acid for dehydration to form a vinylogous iminium intermediate in situ was developed with Pd(OCOCF3)2/(R)-H8-BINAP as catalyst with up to 97% ee. This methodology provides an efficient and rapid access to chiral 2,3-disubstituted indolines.

Highly Enantioselective Partial Hydrogenation of Simple Pyrroles: A Facile Access to Chiral 1-Pyrrolines

A highly enantioselective Pd-catalyzed partial hydrogenation of simple 2,5-disubstituted pyrroles with a Brønsted acid as an activator has been successfully developed, providing chiral 2,5-disubstituted 1-pyrrolines with up to 92% ee.

An Enantioselective Approach to 2,3-Disubstituted Indolines through Consecutive Brønsted Acid/Pd-Complex-Promoted Tandem Reactions

Tandem reactions and consecutive catalysis (or relay catalysis) have been receiving considerable attention in organic synthesis due to their abilities of constructing multiple new chemical bonds to build complex chiral molecules in a single operation. Transition-metal-catalyzed asymmetric hydrogenation is one of the most widely used and reliable catalytic methods for preparation of chiral molecules. The combination of Brønsted acid/transition-metal-catalyzed tandem reactions involving asymmetric hydrogenation as key step remains rare, although Krische and co-workers reported the C C bond formation with metal hydride as the catalytic species. Chiral 2,3-disubstituted indolines are significant building blocks in biologically active natural products and pharmaceutically active compounds. Generally, these compounds are synthesized from either dynamic resolution or multiplestep reactions. The most straightforward and atom economic means towards chiral indolines may be the asymmetric hydrogenation of substituted indole derivatives. Recently, some significant progress has been achieved by us and other groups for the highly enantioselective hydrogenation of substituted indoles using chiral Pd, Rh, Ru, and Ir complexes as catalysts. Very recently, we developed a facile approach to chiral 2,3-disubstituted indolines through dehydration-triggered asymmetric hydrogenation of 3-(a-hydroxyalkyl)indoles. Despite these contributions, the tedious procedure for the preparation of the substrates limits its synthetic applications. So, the search for a rapid, simple, and divergent method for synthesizing chiral 2,3-disubstituted indolines is still highly desirable. Considering reductive alkylation (Friedel–Crafts/dehydration/reduction) of 2-substituted indoles and aldehydes can rapidly lead to 2,3-disubstituted indoles, we envisioned that combination of reductive alkylation of 2-substituted indoles and asymmetric hydrogenation of 2,3-disubstituted indoles can lead to a rapid and divergent approach to chiral 2,3-disubstituted indolines (Scheme 1). Herein, we describe the enantioselective access to chiral 2,3-disubstituted indolines through consecutive Brønsted acid/Pd-complex-

Enantioselective Pd-catalyzed hydrogenation of fluorinated imines: facile access to chiral fluorinated amines.

An enantioselective hydrogenation of simple fluorinated imines has been developed using Pd(OCOCF(3))(2)/(R)-Cl-MeO-BIPHEP as a catalyst, and up to 94% ee was achieved. This method provides an efficient route to enantioenriched fluorinated amines.

Highly effective and diastereoselective synthesis of axially chiral bis-sulfoxide ligands via oxidative aryl coupling.

A series of axially chiral bis-sulfoxide ligands have been efficiently synthesized via oxidative coupling with high diastereoselectivities. The axial chirality is well controlled by the tert-butylsulfinyl or the p-tolylsulfinyl group. These axially chiral bis-sulfoxides proved to be remarkably efficient ligands for the rhodium-catalyzed asymmetric 1,4-addition of arylboronic acids to 2-cyclohexenone with 99% ee.

Enantioselective Pd-catalyzed hydrogenation of enesulfonamides

Asymmetric hydrogenation of cyclic enesulfonamides affords chiral cyclic sulfonamides using Pd(OCOCF(3))(2)/diphosphine complexes as catalysts with up to 98% ee.