The development of a chiral-at-metal iridium(III) complex for the highly efficient catalytic asymmetric transfer hydrogenation of β,β'-disubstituted nitroalkenes is reported. Catalysis by this inert, rigid metal complex does not involve any direct metal coordination but operates exclusively through weak interactions with functional groups properly arranged in the ligand sphere of the iridium complex. Although the iridium complex relies only on the formation of three hydrogen bonds, it exceeds the performance of most organocatalysts with respect to enantiomeric excess (up to 99% ee) and catalyst loading (down to 0.1 mol %). This work hints at an advantage of structurally complicated rigid scaffolds for non-covalent catalysis, which especially relies on conformationally constrained cooperative interactions between the catalyst and substrates.

Asymmetric catalysts, whether metal complexes with chiral ligands, chiral organometallics, or chiral organic compounds (organocatalysts), achieve asymmetric induction by transferring chiral information from the catalyst to the substrate(s). [1] The source of the catalysts chirality therefore plays a crucial role for its mode of action, and is typically derived from one or more tetrahedral stereogenic centers (mostly carbon atoms, but also heteroatoms, such as sulfur or phosphorus), axial chirality, planar chirality, or a combination thereof (Scheme 1). In contrast, only few reports exist of asymmetric catalysts that derive their chirality exclusively from an octahedral stereocenter. [2][3][4] This seems surprising, considering the prevalence of the octahedral coordination geometry in chemistry and its ability to support the generation of structures with high complexity and, as a result of ligand crowding and chelate effects, often low conformational flexibility. [5] We recently demonstrated the use of chiral-atmetal octahedral complexes for the tailored design of a highly efficient asymmetric noncovalent catalyst that requires low catalyst loading by reporting an inert iridium(III)-based catalyst for the conjugate asymmetric transfer hydrogenation of b,b-disubstituted nitroalkenes. [6] However, excellent metal-, bio-, and organo-catalysts already exist for this transformation, [7] and we were therefore wondering whether an octahedral chiral-at-metal catalyst could be developed for a more challenging asymmetric conversion. In this respect, the asymmetric conjugate addition of carbon nucleophiles to b,b-disubstituted nitroalkenes constitutes a highly attractive reaction as it permits the construction of a stereogenic carbon atom bound to four other carbon substituents (all-carbon quaternary stereocenter). [8] Only a handful of studies are available dealing with this particular reaction, thereby presumably reflecting the involved challenge of overcoming a significant steric repulsion between the incoming carbon nucleophile and the carbon substituents of the nitroalkene electrophile. Nevertheless, Hoveyda and co-workers introduced a Cu-catalyzed dialkylzinc conjugate addition, [9] Arai and co-workers reported a Cu-catalyzed addition of indoles to isatin-derived nitroalkenes, [10] Jia and co-workers disclosed a Ni-catalyzed addition of indoles to b-CF 3 -b-disubstituted nitroalkenes, [11] Ricci and co-workers reported a phase-transfer asymmetric organocatalytic conjugate addition of cyanide to b,b-disubstituted nitroalkenes, albeit with only modest enantioselectivities, [12] Melchiorre and co-workers introduced the asymmetric vinylogous Michael addition of cyclic enones to nitroalkenes catalyzed by natural cinchona alkaloids, including one reaction using a b,b-disubstituted nitroalkene, [13] and finally Kastl and Wennemers introduced a proline-peptide-catalyzed asymmetric addition of aldehydes to b,b-disubstituted nitroalkenes under formation of g-nitroaldehydes. [14] The restricted scope of dialkylzinc reagents and t...

A polypyrrole (Ppy)/graphene (G) composite was developed and applied as a novel coating for use in solid-phase microextraction (SPME) coupled with gas chromatography (GC). The Ppy/G-coated fiber was prepared by electrochemically polymerizing pyrrole and G on a stainless-steel wire. The extraction efficiency of Ppy/G-coated fiber for five phenols was the highest compared with the fibers coated with either Ppy or Ppy/graphene oxide (GO) using the same method preparation. Significantly, compared with various commercial fibers, the extraction efficiency of Ppy/G-coated fiber is better than or comparable to 85 μm CAR/PDMS fiber (best extraction efficiency of phenol, o-cresol, and m-cresol in commercial fibers) and 85 μm polyacrylate (PA) fiber (best extraction efficiency of 2,4-dichlorophenol and p-bromophenol in commercial fibers). The effects of extraction and desorption parameters such as extraction time, stirring rate, and desorption temperature and time on the extraction/desorption efficiency were investigated and optimized. The calibration curves were linear from 10 to 1000 μg/L for o-cresol, m-cresol, p-bromophenol, and 2,4-dichlorophenol, and from 50 to 1000 μg/L for phenol. The detection limits were within the range 0.34-3.4 μg/L. The single fiber and fiber-to-fiber reproducibilities were <8.3 (n=7) and 13.3% (n=4), respectively. The recovery of the phenols spiked in natural water samples at 200 μg/L ranged from 74.1 to 103.9% and the relative standard deviations were <3.7%.

Based on a metal-templated approach using a rigid and globular structural scaffold in the form of a bis-cyclometalated octahedral iridium complex, an exceptionally active hydrogen-bond-mediated asymmetric catalyst was developed and its mode of action investigated by crystallography, NMR, computation, kinetic experiments, comparison with a rhodium congener, and reactions in the presence of competing H-bond donors and acceptors. Relying exclusively on weak forces, the enantioselective conjugate reduction of nitroalkenes can be executed at catalyst loadings as low as 0.004 mol% (40 ppm), representing turnover numbers of up to 20 250. A rate acceleration by the catalyst of 2.5 × 10(5) was determined. The origin of the catalysis is traced to an effective stabilization of developing charges in the transition state by carefully orchestrated hydrogen-bonding and van der Waals interactions between catalyst and substrates. This study demonstrates that the proficiency of asymmetric catalysis merely driven by hydrogen-bonding and van der Waals interactions can rival traditional activation through direct transition metal coordination of the substrate.

All reactions were carried out under an atmosphere of argon with magnetic stirring. Solvents were distilled under argon from calcium hydride (CH3CN and CH2Cl2) or sodium/benzophenone (Et2O, THF and toluene). Iridium catalyst Λ-Ir1, 1 pyridylpyrazole L1, 1 bispyrazole L2 2 and the β,β-disubstituted nitroalkene substrates 1,3,4 were prepared according to published procedures. All other reagents were purchased from commercial suppliers (TCI, Aldrich, Alfa and J&K) and used without further purification. Column chromatography was performed with silica gel from Huanghai Chemical Reagent (300-400 mesh). 1 H and 13 C NMR spectra were recorded on a Bruker AM ( 400MHz or 500 MHz) spectrometer at ambient temperature. NMR standards were used as follows: ( 1 H NMR) CDCl3 = 7.26 ppm, CD2Cl2 = 5.32 ppm; ( 13 C NMR) CDCl3 = 77.0 ppm, CD2Cl2 = 53.8 ppm.IR spectra were recorded on a Nicolet Avatar 330 FT-IR spectrophotometer. Chiral HPLC chromatograms were obtained from an Agilent 1260 Series HPLC system. CD spectra were recorded on a JASCO J-810 CD spectropolarimeter (600-200 nm, 1 nm band width, 50 nm/min scanning speed, accumulation of 3 scans). High-resolution mass spectra were recorded on a Bruker En Apex Ultra 7.0T FT-MS instrument using ESI technique. Enantiomeric excess (ee) values of the products were determined by HPLC on chiral phase. S3 Preparation of the Iridium Catalysts Synthesis of the Cyclometalating Ligands L3 and (R)-L4Scheme S1. Synthetic route to the cyclometalating ligand L3.A suspension of 9H-carbazole (7.26 g, 60.0 mmol) and K2CO3 (41.46 g, 300.0 mmol) in DMSO (150 mL) was stirred at room temperature for 1 h. 2-Fluorobenzonitrile (10.03 g, 60.0 mmol) was added and stirred at 150 °C overnight. After cooled to room temperature, the reaction mixture was poured into ice water (300 mL). Then the reaction mixture was extracted with ethyl acetate (3 x 100 mL). The combined organic layer was washed with brine (3 x 200 mL) and then dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The residue was washed by the mixture of n-hexane and ethyl acetate (v/v = 20/1, 3 x 50 mL) to afford the compound S1 as a white solid (14.71 g, 54.9 mmol, 91% yield).

Readily available 1,2-amino alcohols provide the framework for a new generation of chiral carboxylic acid catalysts that rival the acidity of the widely used chiral phosphoric acid catalyst (S)-TRIP. Covalently linked thiourea sites stabilize the carboxylate conjugate bases of these catalysts via anion-binding, an interaction that is largely responsible for the low pK a values. The utility of the new catalysts is illustrated in the context of challenging [4 + 2] cycloadditions of salicylaldehyde-derived acetals with homoallylic and bishomoallylic alcohols, providing polycyclic chromanes in a highly enantioselective fashion.

Organocatalyzed asymmetric Friedel-Craft reactions have enabled the rapid construction of chiral molecules with highly enantioselectivity enriching the toolbox of chemists for producing complex substances. Here, we report N-heterocyclic carbene-catalyzed asymmetric indole Friedel-Crafts alkylation-annulation with α,β-unsaturated acyl azolium as the key intermediate, affording a large variety of indole-fused polycyclic alkaloids with excellent diastereo-and enantioselectivities. The reaction mechanism is also investigated, and the reaction products can be easily converted to highly functionalized indole frameworks with different core structures.

Metall‐vermittelte Organokatalyse: Der enantioselektive Aufbau quartärer Stereozentren wird durch die Ligandensphäre eines inerten bis‐cyclometallierten Iridiumkomplexes (siehe Bild) katalysiert. In diesem Komplex dient allein die metallzentrierte Chiralität als Quelle für die effektive asymmetrische Induktion.