A chiral secondary amine phosphoramide was developed and identified as a powerful catalyst for the Mukaiyama–Michael addition of fluorinated enol silyl ethers to tetrasubstituted olefins. The resulting products are obtained with high enantioselectivities and contain a quaternary carbon stereocenter bearing either a difluoroalkyl or monofluoroalkyl group.

A chiral secondary amine phosphoramide was developed and identified as a powerful catalyst for the Mukaiyama–Michael addition of fluorinated enol silyl ethers to tetrasubstituted olefins. The resulting products are obtained with high enantioselectivities and contain a quaternary carbon stereocenter bearing either a difluoroalkyl or monofluoroalkyl group.

We report an organocatalytic addition of nitromethane to aryl α-ketoester-derived N-tosyl ketimines or isatin-derived N-tert-butyloxycarbonyl ketimines, catalyzed by 1,8-diazabicyclo[5.4.0]undec-7-ene (1–5 mol %). Initial screenings reveal that the reaction with a quinine-derived bifunctional catalyst, which features a C6 phenolic hydroxy group, achieved up to 71 % ee.

A rare example of a one-pot process that involves asymmetric triple relay catalysis is reported. The key step is an asymmetric [1,5] electrocyclic reaction of functionalized ketimines. The substrates for this process were obtained in situ in a two-step process that involved the hydrogenation of nitroarenes with a Pd/C catalyst to yield aryl amines and their subsequent coupling with isatin derivatives in a Brønsted acid catalyzed ketimine formation reaction. The electrocyclization was catalyzed by a bifunctional chiral Brønsted base/hydrogen bond donor catalyst. The one-pot process gave the desired products in good yields and with excellent enantioselectivity.

A rare example of a one-pot process that involves asymmetric triple relay catalysis is reported. The key step is an asymmetric [1,5] electrocyclic reaction of functionalized ketimines. The substrates for this process were obtained in situ in a two-step process that involved the hydrogenation of nitroarenes with a Pd/C catalyst to yield aryl amines and their subsequent coupling with isatin derivatives in a Brønsted acid catalyzed ketimine formation reaction. The electrocyclization was catalyzed by a bifunctional chiral Brønsted base/hydrogen bond donor catalyst. The one-pot process gave the desired products in good yields and with excellent enantioselectivity.

A remarkable fluorine effect on “on water” reactions is reported. The CF⋅⋅⋅HO interactions between suitably fluorinated nucleophiles and the hydrogen-bond network at the phase boundary of oil droplets enable the formation of a unique microstructure to facilitate on water catalyst-free reactions, which are difficult to realize using nonfluorinated substrates. Accordingly, a highly efficient on water, catalyst-free reaction of difluoroenoxysilanes with aldehydes, activated ketones, and isatylidene malononitriles was developed, thus leading to the highly efficient synthesis of a variety of α,α-difluoro-β-hydroxy ketones and quaternary oxindoles.

gem-Difluoroalkyl groups, characterized as a gem-difluoromethylene group substituted by a hydrogen atom or an alkyl or other functional group, are not only valuable for the modulation of the properties of organic compounds, but are also useful for the synthesis of various fluorine-containing compounds. Currently, the catalytic asymmetric construction of stereogenic carbon centers that feature a gem-difluoroalkyl group is in its infancy. This Focus Review summarizes the latest achievements and discusses the difficulties and challenges in this field.

We report the first example of catalytic asymmetric Morita-Baylis-Hillman reaction of acrolein with aromatic aldehydes. The use of 10 mol% of Hatakeyama's catalyst β-isocupreidine C4, in combination with 20 mol% of 2,6-dimethoxybenzoic acid, could catalyze the reaction to give the desired products in up to 81% ee.

We report a highly efficient Friedel–Crafts reaction of 3-alkyl or 3-aryl 3-hydroxyoxindoles with a variety of aromatic and heteroaromatic compounds to unsymmetrical 3,3-diaryloxindoles or 3-alkyl-3-aryloxindoles, which are interesting medicinal targets and useful building blocks for the synthesis of natural products. Hg(ClO₄)₂⋅3 H₂O was identified as a powerful catalyst for this reaction, and is significantly more efficient than other screened metal perchlorate hydrates and Brønsted acids such as HOTf and HClO₄. The high catalytic property of Hg(ClO₄)₂⋅3 H₂O originates from the unprecedented dual activation effects of aromatic mercuration, which could generate a strong protic acid to facilitate the generation of a carbocation at the C3-position of oxindoles and simultaneously form the more reactive nucleophilic reaction partner.

The bifunctional quinine-derived thiourea catalyst 14 was found to catalyze the direct amination of unprotected 3-aryl and aliphatic substituted oxindoles with di-tert-butyl azodicarboxylate (DBAD) to construct a tetrasubstituted stereogenic carbon center at the C-3 position of oxindoles in good to excellent yield and enantioselectivity.

The 3,3′-disubstituted oxindole structural motif is a prominent feature in many alkaloid natural products, which include all kinds of tetrasubstituted carbon stereocenters, spirocyclic or not, all-carbon or heteroatom-containing. The catalytic asymmetric synthesis of the tetrasubstituted carbon stereocenter at the C-3 position of the oxindole framework integrates new synthetic methods and chiral catalysts, reflects the latest achievements in asymmetric catalysis, and facilitates the synthesis of sufficient quantities of related compounds as potential medicinal agents and biological probes. This review summarizes the recent progress in this area, and applications in the total synthesis of related bioactive compounds.

Multicatalyst promoted asymmetric tandem reactions have emerged as a powerful strategy to improve the synthetic efficiency. It enables the synthesis of complex molecules with high selectivity from simple starting materials in an almost biomimetic-like way. The use of multiple catalyst systems can enlarge the substrate and reaction scope for the reaction design, improve the reactivity, and benefit the control of selectivity. In this Focus Review, the current achievement of this promising field is discussed, including the advantages and difficulties of this research, and the strategies applied to address these problems.