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A highly general and straightforward approach to access chiral bis(indolyl)methanes (BIMs) bearing quaternary stereocenters has been realized via enantioconvergent dehydrative nucleophilic substitution. A broad range of 3,3’-, 3,2’- and 3,1’-BIMs were obtained under mild conditions with excellent efficiency and enantioselectivity (80 examples, up to 98% yield and >99:1 er). By utilizing racemic 3-indolyl tertiary alcohols as precursors of alkyl electrophiles and indoles as C–H nucleophiles, this organocatalytic strategy avoids pre-activation of substrates and produces water as the only by-product. Mechanistic studies suggest a formal SN1-type pathway enabled by chiral phosphoric acid catalysis. The practicability of the obtained enantioenriched BIMs was demonstrated by versatile further transformation and high antimicrobial activities (3al, MIC: 1 μg/mL).

Herein, we report an enantioselective dehydrative γ-arylation of α-indolyl propargylic alcohols with phenols via organocatalysis, which provides efficient access to chiral tetrasubstituted allenes and naphthopyrans in high yields with excellent regio- and enantioselectivities under mild conditions. This method features the use of cheaply available naphthols/phenols as the C-H aryl source and liberating water as the sole byproduct. Control experiments suggest that the excellent enantioselectivity and remote regioselectivity stem from dual hydrogen-bonding interaction with the chiral phosphoric acid catalyst.

A catalytic asymmetric umpolung cross-Mannich reaction of cyclic ketimines is realized. This protocol provides an efficient methodology for the facile synthesis of chiral vicinal tetrasubstituted diamines in high yields with excellent chemo-, regio-, diastereo-, and enantioselectivities using cinchona-derived bifunctional organocatalysts (85-98% yield, up to >20:1 dr, and >99% ee).

A highly general and straightforward approach to access chiral bis(indolyl)methanes (BIMs) bearing quaternary stereocenters has been realized

Herein, we describe a novel transition metal-free, umpolung strategy for the α-arylation of ketones by capturing transient oxyallyl cations with arylboronic acids. A variety of α-arylated ketones were obtained in moderate to good yields with broad substrate tolerance under simple reaction conditions. This process provides a complementary strategy compared with traditional transition metal-catalyzed methods.

A catalytic asymmetric oxa-1,3-dipolar cycloaddition of ketones with trifluoroethylamine-derived azomethine ylides has been developed using cinchona-derived bifunctional thiourea catalysts. This protocol provides an efficient methodology for the facile synthesis of chiral CF3-containing oxazolidines with moderate to excellent yields, excellent diastereoselectivities and enantioselectivities (58–98% yields, up to >20 : 1 dr and 98% ee). Remarkably, these oxazolidines could be facilely converted to CF3-containing 1,2-amino alcohols with vicinal stereogenic centers, which is a privileged structural motif in medicinal chemistry.

Under bifunctional squaramide and thiourea organocatalysis, a series of vicinally bis(trifluoromethyl)-substituted 3,3′-pyrrolidinyl spirooxindoles were successfully synthesized via 1,3-dipolar cycloaddition reactions of 3-(trifluoroethylidene)oxindoles with diethyl 2-((2,2,2-trifluoroethyl)imino)malonate and N-(2,2,2-trifluoroethyl)isatin ketimines. The highlight of this protocol is the efficient construction of the vicinally bis(trifluoromethyl)-substituted pyrrolidine unit of spirooxindoles, including multiple contiguous stereogenic centres, in excellent yields and stereoselectivities.

An efficient asymmetric Michael/cyclization cascade reaction of 3-isothiocyanato oxindoles with 3-trifluoroethylidene oxindoles has been revealed. Under bifunctional organocatalysis with a cinchona alkaloid derived squaramide catalyst, a series of novel 3′-trifluoromethyl substituted 3,2′-pyrrolidinyl-bispirooxindoles were conveniently constructed in a highly stereoselective manner (up to 96% yield, >20 : 1 dr and >99% ee). The reaction leads to the formation of three contiguous stereogenic centers and two spiro quaternary stereocenters.

A porous MOF constructed from a [Cu2(COO)4] secondary building unit, H3L (H3L = [1,1';3',1'']terphenyl-4,5',4''-tricarboxylic acid), and pyrazine ligands features a unique hendecahedron cage-like cavity with good stability and a high BET surface area of 3235 m(2) g(-1), showing good controlled drug release property of ibuprofen over those of anethole and guaiacol.