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Searching for efficient strategies to access structurally novel aminoindolines is of great significance for drug discovery. However, catalytic asymmetric de novo construction of aminoindoline scaffolds with functionality primed for diversification still remains elusive. Here, we report a Cu-catalyzed asymmetric cyclization of ethynyl benzoxazinones with amines, producing chiral 3-aminoindolines in good yield and with high enantioselectivity (up to 97% yield and 98:2 er). Moreover, a radical-mediated sulfonyl migration of these products was unexpectedly found, further affording new chiral 3-aminoindolines bearing alkenyl sulfonyl groups with retained enantiopurity (up to 84% yield and 98:2 er). Bioactivity evaluations indicate that these 3-aminoindolines show notable antitumor activities and chirality is proven to have a significant impact on their antitumor activity.

Grignard addition is one of the most important methods used for syntheses of alcohol compounds and has been known for over a hundred years. However, research on asymmetric catalysis relies on the use of organometallic nucleophiles. Here, we report the first visible-light-induced cobalt-catalyzed asymmetric reductive Grignard-type addition for synthesizing chiral benzyl alcohols (50 examples, up to 99% yield, and 99% ee). This methodology has the advantages of mild reaction conditions, good functionality tolerance, excellent enantiocontrol, the avoidance of mass metal wastes, and the use of precious metal catalysts. Kinetic realization studies suggested that migratory insertion of an aryl cobalt species into the aldehyde was the rate-determining step of the reductive addition reaction.

The first asymmetric propargylic radical cyanation was realized through a dual photoredox and copper catalysis. An organic photocatalyst serves to both generate propargyl radicals and oxidize Cu(I) species to Cu(II) species. A chiral Cu complex functions as an efficient organometallic catalyst to resemble the propargyl radical and cyanide in an enantio-controlled manner. Thus, a diverse range of optically active propargyl cyanides were produced with high reaction efficiency and enantioselectivities (28 examples, 57-97% yields and 83-98% ee). Moreover, mechanistic investigations including experiments and density functional theory calculations were performed to illustrate on the reaction pathway and stereochemical results.

1,3-Dienes are readily available feedstocks that are widely used in the laboratory and industry. However, the potential of converting 1,3-dienes into value-added products, especially chiral products, has not yet been fully exploited. By synergetic photoredox/copper catalysis, we achieve the first visible-light-induced, enantioselective carbocyanation of 1,3-dienes by using carboxylic acid derivatives and trimethylsilyl cyanide. Under mild and neutral conditions, a diverse range of chiral allyl cyanides are produced in generally good efficiency and with high enantioselectivity from bench-stable and user-safe chemicals. Moreover, preliminary results also confirm that this success can be expanded to 1,3-enynes and the four-component carbonylative carbocyanation of 1,3-dienes and 1,3-enynes.

An enantioselective [5+2] cycloaddition of vinylethylene carbonates and α-diazoketones was achieved for the first time by merging photoactivation and asymmetric Pd catalysis. The key to the success of this method is the enantioselective trapping of Pd-containing, 1,5-dipolar intermediates by ketenes, a class of reactive C2 synthons, which were generated in an in situ and traceless manner under visible light irradiation. Through this trapping, a variety of 7-membered lactones bearing challenging chiral quaternary stereocenters can be accessed in a facile manner with good efficiency and high enantioselectivity (up to 99% yield and 96:4 er).

Splitting of alcohols into hydrogen and corresponding carbonyl compounds has potential applications in hydrogen production and chemical industry. Herein, we report that a heterogeneous photocatalyst (Ni-modified CdS nanoparticles) could efficiently split alcohols into hydrogen and corresponding aldehydes or ketones in a stoichiometric manner under visible light irradiation. Optimized apparent quantum yields of 38%, 46%, and 48% were obtained at 447 nm for dehydrogenation of methanol, ethanol, and 2-propanol, respectively. In the case of dehydrogenation of 2-propanol, a turnover number of greater than 44 000 was achieved. To our knowledge, these are unprecedented values for photocatalytic splitting of liquid alcohols under visible light to date. Besides, the current catalyst system functions well with other aliphatic and aromatic alcohols, affording the corresponding carbonyl compounds with good to excellent conversion and outstanding selectivity. Moreover, mechanistic investigations suggest that an interface between Ni nanocrystal and CdS plays a key role in the reaction mechanism of the photocatalytic splitting of alcohol.

Catalytic asymmetric cycloadditions of reactive ketene intermediates provide new opportunities for the production of chiral heterocyclic molecules. Though known for over 100 years, ketenes still remain underexplored in the field of transition-metal (TM)-catalyzed asymmetric cycloadditions because (1) ketenes, as highly electron-deficient species, are possibly unstable to low-valence TMs (i.e., decarbonylation or aggregation) and (2) the conventional thermal synthesis of ketenes from acyl chlorides and amines may be incompatible with TM catalysis (i.e., reactive acyl chloride and amine hydrochloride byproducts). Herein, we detail the unprecedented asymmetric [4+2] cycloaddition of vinyl benzoxazinanones with a variety of ketene intermediates via sequential visible-light photoactivation and palladium catalysis. It is well demonstrated that the traceless and transient generation of ketenes from α-diazoketones through visible-light-induced Wolff rearrangement is important for the success of present cycloaddition. Furthermore, chiral palladium catalysts with a new, chiral hybrid P, S ligand enable asymmetric cycloaddition with high reaction selectivity and enantiocontrol.

The Wittig reaction, which produces alkenes from phosphorus ylides (P-ylides) and carbonyls, is one of the most powerful tools in chemical synthesis. This Nobel Prize-winning reaction is widely used in natural product synthesis, fine chemical production (i.e., medicines and agricultural agents), and polymer functionalization. Despite these great achievements, the potential of the Wittig reaction, particularly regarding the access of chiral alkene building blocks, has not been fully exploited. The main area that requires additional exploration is the development of general and practical methods to efficiently prepare chiral P-ylides. Here, we show that highly functionalized chiral P-ylides can be easily synthesized through a copper-catalyzed asymmetric propargylic alkylation reaction from phosphonium salts and racemic propargylic esters. The subsequent Wittig reactions enable the synthesis of versatile alkene building blocks, chiral α-propargylic acrylates, and α-propargylic allenoates, with a wide substrate scope and satisfactory functional group compatibility. This transformation features inexpensive transition-metal catalysts, user-friendly conditions, easily available feedstock, and high-valued products.

A novel visible-light-responsive chiral ligand has been developed by grafting a triplet state photosensitizer to chiral bisoxazoline ligands. Complexation of this ligand with Ni(acac)2 results in a powerful catalyst for the asymmetric oxidation reaction of β-ketoesters, which uses oxygen or air as the green oxidant and visible light or sunlight as the ideal driving force. Using this protocol, products containing the α-hydroxy-β-dicarbonyl motif are produced in high yields and with excellent enantiopurities.

The first copper-catalyzed asymmetric decarboxylative [4 + 1] cycloaddition of propargylic carbamates and sulfur ylides was successfully developed. This strategy led to a series of chiral indolines with synthetically flexible alkyne groups in good yields and with high enantio- and diastereoselectivities (up to 99% yield, 98% ee, and >95:5 dr). A possible mechanism and stereoinduction mode with copper-allenylidenes were proposed as the possible dipolar intermediate.

An asymmetric hydrogenation reaction of benzoxazinones has been accomplished via a relay iron/chiral Bronsted acid catalysis. This approach provides a variety of chiral dihydrobenzoxazinones in good to high yields (75–96%) and enantioselectivities (up to 98:2 er). It is noteworthy that challenging 3-alkyl-substituted substrates underwent highly enantioselective reduction. A key to success is the utilization of a nonchiral phosphine ligand to reduce disadvantageous background reactions through tuning the catalytic activity of Fe3(CO)12.

Unprecedented chemoselective reductions of phosphine oxides to phosphines proceed smoothly in the presence of catalytic amounts of specific Bronsted acids. By utilizing inexpensive silanes, e.g., PMHS or (EtO)(2)MeSiH, other reducible functional groups such as ketones, aldehydes, olefins, nitriles, and esters are well-tolerated under optimized conditions.

A novel cascade organocatalysis that allows efficient and rapid access to diverse and structurally complex oxazolidin-2-ones from simple starting materials and catalysts has been developed. A possible mechanism of this reaction has been proposed based on D- and 13C-labeling experiments.