Organocatalytic Atroposelective Friedländer Quinoline Heteroannulation.

An atroposelective Friedländer heteroannulation reaction of 2-aminoaryl ketones with α-methylene carbonyl derivatives has been developed for the first time with chiral phosphoric acid as an efficient organocatalyst. The desired enantioenriched axially chiral polysubstituted 4-arylquinoline architectures were prepared with good to high yields and enantioselectivities (up to 94% yield and up to 97% ee). Furthermore, the products can be readily derivatized to afford an array of new quinoline-containing heteroatropisomers, which hold great potential in asymmetric catalysis and drug discovery.

Highly Atroposelective Synthesis of Arylpyrroles by Catalytic Asymmetric Paal-Knorr Reaction.

A general and efficient method for accessing enantiomerically pure arylpyrroles by utilizing the catalytic asymmetric Paal-Knorr reaction has been developed for the first time. A wide range of axially chiral arylpyrroles were obtained in high yields with good to excellent enantioselectivities. The key to success is the use of the combined-acid catalytic system involving a Lewis acid and a chiral phosphoric acid for achieving effective enantiocontrol. Noteworthy is that an unexpected solvent-dependent inversion of the enantioselectivity was observed in the above-mentioned asymmetric reaction.

Phosphoric Acid-Catalyzed Asymmetric Synthesis of SPINOL Derivatives.

Axially chiral 1,1'-spirobiindane-7,7'-diol (SPINOL) is the most fundamental and important privileged structure from which other chiral ligands containing a 1,1'-spirobiindane backbone are synthesized. Driven by the development of enantioselective syntheses of axially chiral SPINOL derivatives, we have successfully developed the first phosphoric acid-catalyzed asymmetric approach. This approach is highly convergent and functional group tolerant, efficiently providing SPINOLs in good yield with excellent enantioselectivity, thus delivering a practical and straightforward access to this privileged structure. It should be emphasized that the catalyst loading could be decreased to only 0.1 mol% for the preparative-scale synthesis. Furthermore, 4,4'-dimethyl-SPINOL-phosphoric acid was synthesized and applied to catalyze the model reaction for synthesis of enantioenriched SPINOL derivatives.

Discovery and enantiocontrol of axially chiral urazoles via organocatalytic tyrosine click reaction.

Axially chiral compounds play an important role in areas such as asymmetric catalysis. The tyrosine click-like reaction is an efficient approach for synthesis of urazoles with potential applications in pharmaceutical and asymmetric catalysis. Here we discover a class of urazole with axial chirality by restricted rotation around an N-Ar bond. By using bifunctional organocatalyst, we successfully develop an organocatalytic asymmetric tyrosine click-like reaction in high yields with excellent enantioselectivity under mild reaction conditions. The excellent remote enantiocontrol of the strategy originates from the efficient discrimination of the two reactive sites in the triazoledione and transferring the stereochemical information of the catalyst into the axial chirality of urazoles at the remote position far from the reactive site.

Atroposelective Synthesis of Axially Chiral Biaryldiols via Organocatalytic Arylation of 2-Naphthols.

The first phosphoric acid-catalyzed asymmetric direct arylative reactions of 2-naphthols with quinone derivatives have been developed, providing efficient access to a class of axially chiral biaryldiols in good yields with excellent enantioselectivities under mild reaction conditions. This approach is a highly convergent and functional group tolerant route to the rapid construction of axially chiral compounds from simple, readily available starting materials. The excellent stereocontrol of the process stems from efficient transfer of stereochemical information from the chiral phosphoric acid into the axis chirality of the biaryldiol products. Preliminary results demonstrate that the biaryldiols can act as efficient chiral ligands in asymmetric transformations.

Phosphoric acid-catalyzed asymmetric classic Passerini reaction.

An efficient enantioselective classic three-component Passerini reaction with a broad substrate scope in the presence of a chiral phosphoric acid catalyst has been developed. This represents the general example for classic three-component Passerini reaction with good to excellent enantioselectivies involving aromatic aldehydes and the bulky pivalaldehyde under mild reaction conditions. The feature of this method is highlighted by using a chiral phosphoric acid to activate carboxylic acid, aldehyde, and isocyanide for the facile construction of widely useful complex compounds.

In situ generation of electrophilic trifluoromethylthio reagents for enantioselective trifluoromethylthiolation of oxindoles.

An organocatalytic asymmetric trifluoromethylthiolation reaction via in situ generation of active electrophilic trifluoromethylthio species involving trichloroisocyanuric acid and AgSCF3 as a practical and easily handled electrophilic SCF3 source for CSP(3)-SCF3 bond formation was developed. Reactions with this one-pot version strategy occurred in good yields and excellent stereoselectivities to access enantiopure oxindoles bearing a SCF3-substituted quaternary chiral center. The straightforward process described here makes use of simple starting materials and proceeds under mild conditions, which will be useful in medicinal chemistry and diversity-oriented syntheses.

Highly enantioselective kinetic resolution of axially chiral BINAM derivatives catalyzed by a Brønsted acid.

A highly efficient strategy for the kinetic resolution of axially chiral BINAM derivatives involving a chiral Brønsted acid-catalyzed imine formation and transfer hydrogenation cascade process was developed. The kinetic resolution provides a convenient route to chiral BINAM derivatives in high yields with excellent enantioselectivities.

Catalytic asymmetric Pictet-Spengler-type reaction for the synthesis of optically active indolo[3,4-cd][1]benzazepines.

A new strategy has been introduced to develop a catalytic asymmetric Pictet-Spengler-type reaction by replacing the aldehyde with an imine. A range of 4-(2-aminoaryl)indoles smoothly undergo the chiral phosphoric acid catalyzed asymmetric Pictet-Spengler-type reaction with imines at room temperature to give structurally diverse indolo[3,4-cd][1]benzazepines in good to excellent yields and ee.

Catalytic regioselective synthesis of structurally diverse indene derivatives from N-benzylic sulfonamides and disubstituted alkynes.

An unprecedented protocol has been developed for the regioselective synthesis of structurally diverse indene derivatives from readily accessible N-benzylic sulfonamides and disubstituted alkynes through FeCl(3)-catalyzed cleavage of sp(3) carbon-nitrogen bonds to generate benzyl cation intermediates. In the presence of 10 mol % of FeCl(3), a broad range of N-benzylic sulfonamides smoothly react with internal alkynes, alkynylcarbonyl compounds, alkynyl chalcogenides, or alkynyl halides to afford various functionalized indene derivatives with extremely high regioselectivity.

Catalyst-free alkylation of sulfinic acids with sulfonamides via sp(3) C-N bond cleavage at room temperature.

An unprecedented catalyst-free alkylation of sulfinic acids with sulfonamides has been developed via sp(3) C-N bond cleavage at room temperature. In the absence of external catalysts and additives, a wide variety of N-benzylic and N-allylic sulfonamides couple with sulfinic acids to give structurally diversified sulfones in moderate to excellent yields. Furthermore, the reaction of N-(2-acyl)allylic sulfonamides with sulfinic acids provides a convenient access to trisubstituted allyl sulfones with exclusive Z selectivity.