Catalytic Asymmetric Ring‐Opening Reactions of Aziridines with 3‐Aryl‐Oxindoles

A highly enantioselective ring‐opening alkylation reaction between 3‐aryl‐oxindole and N‐(2‐picolinoyl) aziridine has been realized for the first time. The reaction is efficiently mediated by a simple in‐situ‐generated magnesium catalyst and 3,3′‐fluorinated‐BINOL (BINOL=1,1′‐binaphthalene‐2,2′‐diol) has been identified as a powerful chiral ligand. Notably, the fluorine atom on the chiral ligand plays a key role in providing the desired chiral 3‐alkyl‐3‐aryl oxindoles with excellent enantioselectivities.     

Modulation of Multifunctional N,O,P Ligands for Enantioselective Copper‐Catalyzed Conjugate Addition of Diethylzinc and Trapping of the Zinc Enolate

In this work, we have successfully synthesized a new family of chiral Schiff base–phosphine ligands derived from chiral binaphthol (BINOL) and chiral primary amine. The controllable synthesis of a novel hexadentate and tetradentate N,O,P ligand that contains both axial and sp³‐central chirality from axial BINOL and sp³‐central primary amine led to the establishment of an efficient multifunctional N,O,P ligand for copper‐catalyzed conjugate addition of an organozinc reagent. In the asymmetric conjugate reaction of organozinc reagents to enones, the polymer‐like bimetallic multinuclear Cu? Zn complex constructed in situ was found to be substrate‐selective and a highly excellent catalyst for diethylzinc reagents in terms of enantioselectivity (up to >99 % ee). More importantly, the chirality matching between different chiral sources, C₂‐axial binaphthol and sp³‐central chiral phosphine, was crucial to the enantioselective induction in this reaction. The experimental results indicated that our chiral ligand (R,S,S)‐ L1 ‐ and (R,S)‐ L4 ‐based bimetallic complex catalyst system exhibited the highest catalytic performance to date in terms of enantioselectivity and conversion even in the presence of 0.005 mol % of catalyst (S/C=20 000, turnover number (TON)=17 600). We also studied the tandem silylation or acylation of enantiomerically enriched zinc enolates that formed in situ from copper‐ L4 ‐complex‐catalyzed conjugate addition, which resulted in the high‐yield synthesis of chiral silyl enol ethers and enoacetates, respectively. Furthermore, the specialized structure of the present multifunctional N,O,P ligand L1 or L4 , and the corresponding mechanistic study of the copper catalyst system were investigated by ³¹P NMR spectroscopy, circular dichroism (CD), and UV/Vis absorption.     

Iron‐Catalyzed Highly Enantioselective cis‐Dihydroxylation of Trisubstituted Alkenes with Aqueous H2O2

Reliable methods for enantioselective cis‐dihydroxylation of trisubstituted alkenes are scarce. The iron(II) complex cis‐α‐[Fe^II(2‐Me₂‐BQPN)(OTf)₂], which bears a tetradentate N₄ ligand (Me₂‐BQPN=(R,R)‐N,N′‐dimethyl‐N,N′‐bis(2‐methylquinolin‐8‐yl)‐1,2‐diphenylethane‐1,2‐diamine), was prepared and characterized. With this complex as the catalyst, a broad range of trisubstituted electron‐deficient alkenes were efficiently oxidized to chiral cis‐diols in yields of up to 98 % and up to 99.9 % ee when using hydrogen peroxide (H₂O₂) as oxidant under mild conditions. Experimental studies (including ¹⁸O‐labeling, ESI‐MS, NMR, EPR, and UV/Vis analyses) and DFT calculations were performed to gain mechanistic insight, which suggested possible involvement of a chiral cis‐Fe^V(O)₂ reaction intermediate as an active oxidant. This cis‐[Fe^II(chiral N₄ ligand)]²⁺/H₂O₂ method could be a viable green alternative/complement to the existing OsO₄‐based methods for asymmetric alkene dihydroxylation reactions.     

Enantioselective Dehydrogenation of Alkan‐2‐ols by Gaseous (BINOLate)Ni+

Electrospray ionization of methanolic solutions of nickel(II) nitrate, 1,1′‐binaphthalene‐2,2′‐diol (BINOL), and secondary alcohols (ROH) inter alia affords monocationic complexes of the type [(BINOLate)Ni(ROH)]⁺, where BINOLate stands for singly deprotonated BINOL. Upon collision‐induced dissociation (CID), the mass‐selected ions undergo competing fragmentations involving loss of the alcohol ligand and expulsion of the corresponding carbonyl compound. The latter reaction leads to the hydride complex [(BINOL)Ni(H)]⁺ and can thus be regarded as the reversal of the reduction of ketones with metal hydrides. The possibility of the occurrence of enantioselective gas‐phase reactions is probed for combinations of chiral BINOLate ligands with chiral alkan‐2‐ols. Whereas aliphatic alkan‐2‐ols do not show pronounced chiral effects, enantioselective bond activation is observed for 1‐phenylethanol, indicating an interaction of the aromatic ring of the alkanol with the positively charged metal center.     

Development of Asymmetric Reactions Catalyzed by Chiral Organotin‐Alkoxide Reagents

Asymmetric catalysis under almost‐neutral reaction conditions is key for the efficient synthesis of optically active polar molecules. We have developed catalytic enantioselective reactions of acyclic or cyclic alkenyl esters by using an (S)‐BINOL‐derived chiral tin‐dibromide reagent that possesses a bulky aryl group at the 3 or 3′ position as the chiral pre‐catalyst in the presence of a sodium alkoxide and an alcohol, in which a chiral tin alkoxide bromide is generated in situ and recycled with the assistance of an alcohol. In this Personal Account, we describe three types of asymmetric transformation that proceed through a chiral tin enolate: 1) The asymmetric aldol reaction of alkenyl esters or unsaturated lactones with aldehydes or isatins; 2) the asymmetric three‐component Mannich‐type reaction of alkenyl esters and related cycloaddition reactions; and 3) the asymmetric N‐nitroso aldol reaction of unsaturated lactones with nitrosoarenes.     

Bimetallic Gold(I)/Chiral N,N′‐Dioxide Nickel(II) Asymmetric Relay Catalysis: Chemo‐ and Enantioselective Synthesis of Spiroketals and Spiroaminals

A highly efficient asymmetric cascade reaction between keto esters and alkynyl alcohols and amides is reported. The success of the reaction was attributed to the combination of chiral Lewis acid N,N′‐dioxide nickel(II) catalysis with achiral π‐acid gold(I) catalysis working as an asymmetric relay catalytic system. The corresponding spiroketals and spiroaminals were synthesized in up to 99 % yield, 19:1 d.r., and more than 99 % ee under mild reaction conditions. Control experiments suggest that the N,N′‐dioxide ligand was essential for the formation of the spiro products.     

Ligand‐Accelerated Direct C−H Arylation of BINOL: A Rapid One‐Step Synthesis of Racemic 3,3′‐Diaryl BINOLs

An ortho‐selective rhodium‐catalyzed direct C?H arylation of 1,1′‐bi‐2‐naphthol (BINOL), to deliver the widely used but not easily available 3,3′‐diaryl BINOL, has been developed. This highly efficient one‐step synthetic approach is the shortest route to date and is greatly facilitated by the newly developed ligand system comprising tBu₂PCl, Ph₂‐cod, and Cy₃P?HBF₄. In addition, the same procedure can facilitate the challenging syntheses of 3‐bulkyaryl BINOLs in good to excellent yields.     

Chiral Phosphate in Rhodium‐Catalyzed Asymmetric [2+2+2] Cycloaddition: Ligand,Counterion, or Both?

Investigations based on NMR spectroscopy, mass spectrometry, and DFT calculations shed light on the metallic species generated in the rhodium‐catalyzed asymmetric [2+2+2] cycloaddition reaction between diynes and isocyanates with the chiral phosphate TRIP. The catalytic mixture comprising [{Rh(cod)Cl}₂], 1,4‐diphenylphosphinobutane (dppb), and Ag(S)‐TRIP actually gives rise to two species, both having an effect on the stereoselectivity. One is a rhodium(I) complex in which TRIP is a weakly coordinating counterion, whereas the other is a bimetallic Rh/Ag complex in which TRIP is a strongly coordinating X‐type ligand.     

Highly Enantioselective Hydrogenation of Cyclic Enol Acetates Catalyzed by a Rh–PennPhos Complex

The electron‐rich and conformationally rigid (R,S,R,S)‐Me‐PennPhos ligand (shown schematically) appears to chelate rhodium and form well‐defined chiral pockets. This allows, for example, efficient differentiation between the two enantiotopic approaches available to a substrate in a hydrogenation reaction. The Rh–Me‐PennPhos complex is the first catalyst for the highly enantioselective asymmetric hydrogenation of cyclic enol acetates. For example, 3,4‐dihydronaphth‐1‐yl acetate can be hydrogenated with up to 99% ee.     

Phosphines versus phosphinites as ligands in the rhodium catalyzed asymmetric hydrogenation of imines: a systematic study

The asymmetric hydrogenation of N-(1-phenylethylidene)benzylamine with a range of rhodium(I)-diphosphine and diphosphinite catalysts is studied. The reaction is strongly sensitive to the size of the metal chelate. Complexes based on five- and six-membered chelates or electron-rich alkylphosphines gave poor or moderate conversions. The reactivity of diphosphine catalysts could be increased by the addition of p-toluenesulfonic acid. Unexpectedly, Rh-complexes based on chiral diphosphinites and a diphosphite also rapidly converted the substrate to the desired amine. Highest efficiency was observed with a rhodium(I) complex with (R,R)-1,2-cyclohexanol-bisdiphenylphosphinite [(R,R)-bdpch] as chiral ligand. Without any additive complete hydrogenation of the imine was achieved within 5 h. The product was produced in an enantioselectivity of 71%.     

Rhodium/Chiral Diene‐Catalyzed Asymmetric 1,4‐Addition of Arylboronic Acids to Chromones: A Highly Enantioselective Pathway for Accessing Chiral Flavanones

Chromone has been noted to be one of the most challenging substrates in the asymmetric 1,4‐addition of α,β‐unsaturated carbonyl compounds. By employing the rhodium complex associated with a chiral diene ligand, (R,R)‐Ph‐bod*, the 1,4‐addition of a variety of arylboronic acids was realized to give high yields of the corresponding flavanones with excellent enantioselectivities (≥97 % ee, 99 % ee for most substrates). Ring‐opening side products, which would lead to erosion of product enantioselectivity, were not observed under the stated reaction conditions.     

New chiral diphosphoramidite rhodium(I) complexes for asymmetric hydrogenation

Chiral 1,5‐cyclooctadiene rhodium(I) cationic complexes with C₂‐symmetric chelate diphosphoramidite ligands containing (R,R)‐1,2‐diaminocyclohexane as the backbone and two atropoisomeric biaryl units were easily synthesized and fully characterized by multinuclear one‐ and two‐dimensional NMR spectroscopy and elemental analysis. These complexes were used as catalysts in the asymmetric hydrogenation of dimethyl itaconate, methyl 2‐acetamidoacrylate and (Z)‐methyl‐2‐acetamido‐3‐phenylacrylate. The rhodium complexes derived from diphosphoramidite ligands that contain two (R) or (S) BINOL (2,2′‐dihydroxy‐1,1′‐binaphthyl) units proved to be efficient catalysts, giving complete conversion and very good enantioselectivity (up to 88% ee). An uncommon positive H₂ pressure effect on the enantioselectivity was observed in the hydrogenation of dimethyl itaconate catalyzed by Rh‐complex with diphosphoramidite ligand that contains two (S)‐binaphthol moieties. Copyright © 2014 John Wiley & Sons, Ltd.     

Functionalized Periodic Mesoporous Organosilica: A Highly Enantioselective Catalyst for the Michael Addition of 1,3‐Dicarbonyl Compounds to Nitroalkenes

A functionalized periodic mesoporous organosilica with incorporated chiral bis(cyclohexyldiamine)‐based Ni^II complexes within the silica framework was developed by the co‐condensation of (1R,2R)‐cyclohexyldiamine‐derived silane and ethylene‐bridge silane, followed by the complexation of NiBr₂ in the presence of (1R,2R)‐N,N′‐dibenzylcyclohexyldiamine. Structural characterization by XRD, nitrogen sorption, and TEM disclosed its orderly mesostructure, and FTIR and solid‐state NMR spectroscopy demonstrated the incorporation of well‐defined single‐site bis(cyclohexyldiamine)‐based Ni^II active centers within periodic mesoporous organosilica. As a chiral heterogeneous catalyst, this functionalized periodic mesoporous organosilica showed high catalytic activity and excellent enantioselectivity in the asymmetric Michael addition of 1,3‐dicarbonyl compounds to nitroalkenes, comparable to those with homogeneous catalysts. In particular, this heterogeneous catalyst could be recovered easily and reused repeatedly up to nine times without obviously affecting its enantioselectivity, thus showing good potential for industrial applications.     

New Chiral Ligand N—Toluenesulfony1—2,2‘—dimethoxy—6,6’—di—aminobiphenyl for Catalytic Asymmetric Transfer Hydrogenation of Ketones

A new chiral ligand N‐p‐toluenesulfonyl‐2,2′‐dimethoxy‐6,6′‐diaminobiphenyl (Ts‐DMBDPPA) was prepared from 2,2′‐dimethoxy‐6,6′‐diaminobiphenyl via N‐tosylation. Its Ru(II) complex was effective catalysts for catalytic asymmetric transfer hydrogenation of aromatic ketones (with ee's up to 69.3%).     

Secondary Interactions or Ligand Scrambling? Subtle Steric Effects Govern the Iridium(I) Coordination Chemistry of Phosphoramidite Ligands

The like and unlike isomers of phosphoramidite (P*) ligands are found to react differently with iridium(I), which is a key to explaining the apparently inconsistent results obtained by us and other research groups in a variety of catalytic reactions. Thus, the unlike diastereoisomer (aR,S,S)‐[IrCl(cod)( 1 a )] ( 2 a ; cod=1,5‐cyclooctadiene, 1 a =(aR,S,S)‐(1,1′‐binaphthalene)‐2,2′‐diyl bis(1‐phenylethyl)phosphoramidite) forms, upon chloride abstraction, the monosubstituted complex (aR,S,S)‐[Ir(cod)(1,2‐η‐ 1 a ,κP)]⁺ ( 3 a ), which contains a chelating P* ligand that features an η² interaction between a dangling phenyl group and iridium. Under analogous conditions, the like analogue (aR,R,R)‐ 1 a′ gives the disubstituted species (aR,R,R)‐[Ir(cod)( 1 a′ ,κP)₂]⁺ ( 4 a′ ) with monodentate P* ligands. The structure of 3 a was assessed by a combination of X‐ray and NMR spectroscopic studies, which indicate that it is the configuration of the binaphthol moiety (and not that of the dangling benzyl N groups) that determines the configuration of the complex. The effect of the relative configuration of the P* ligand on its iridium(I) coordination chemistry is discussed in the context of our preliminary catalytic results and of apparently random results obtained by other groups in the iridium(I)‐catalyzed asymmetric allylic alkylation of allylic acetates and in rhodium(I)‐catalyzed asymmetric cycloaddition reactions. Further studies with the unlike ligand (aS,R,R)‐(1,1′‐binaphthalene)‐2,2′‐diyl bis{[1‐(1‐naphthalene‐1‐yl)ethyl]phosphoramidite} ( 1 b ) showed a yet different coordination mode, that is, the η⁴‐arene–metal interaction in (aS,R,R)‐[Ir(cod)(1,2,3,4‐η‐ 1 b ,κP)]⁺ ( 3 b ).     

Copper(II)‐Catalyzed Nitroaldol (Henry) Reactions: Recent Developments

Self‐assembled copper(II) complexes are described as effective catalysts for nitroaldol (Henry) reactions on water. The protocol involves a heterogeneous process and the catalysts can be recovered and recycled without loss of activity. Further, C2‐symmetric N,N′‐substituted chiral copper(II) salan complexes are found to be more effective catalysts than chiral copper(II) salen complexes for reactions in homogeneous catalysis, with high enantioselectivities. The reactions involve bifunctional catalysis, bearing the properties of a Brønsted base, as well as a Lewis acid, to effect the reaction in the absence of external additives.     

Silica Hybrid Containing （ R ）-2, 2＇-Binaphtho-20-crown-6 Moieties via the Sol-Gel Process

(R)-6,6‘-Bis(triethoxysilylethen-2-yl)-2,2-‘binaphtho-20-crown-6(precursor,R-2) derived form(R)-2,2-BINOL derivative was synthesized by Pd-catelyzed Heck reaction of (R)-6-6‘-dibromo-2,2‘-binaphtoh-20-crown-6(R-1) intermediate with vinyltriethoxysilane. The hydrolysis and polycondensatlon ofthe precursor gave rise to the corresponding xerogei. Both pre cursor and xerogei were analysed by NMR, FT-IR, UV, CD spectra, fluorescent spectroscopy, polarimetry and elemental analysis. The precursor and xerogei can emit strong blue fluorescenee and are expected to have the potential appficatiou inthe separation of chiral molecules as fluorescent sensor. The precursor exhibits strong Cotton effect in its circular dichroism (CD) spectrum indicating that it is a highly rigid structure.     

Asymmetric Henry reactions of aldehydes with various nitroalkanes catalyzed by copper(II) complexes of novel chiral N‐monoalkyl cyclohexane‐1,2‐diamines

A number of novel chiral diamines 3 , (1R,2R)‐N‐monoalkylcyclohexane‐1,2‐diamines, were designed and synthesized from trans‐cyclohexane‐1,2‐diamine and applied to the catalytic asymmetric Henry reaction of benzaldehyde and nitromethane to provide β‐nitroalcohol in high yield (up to 99%) and good enantiomeric excess (up to 89%). By using ligand (1R,2R)‐N¹‐(4‐methylpentan‐2‐yl)cyclohexane‐1,2‐diamine ( 3g ), the reaction was optimized in terms of the metal ion, temperature, solvent and base. Further experiments indicated that the complex, 3g –Cu(OAc)₂, was an efficient catalyst in the asymmetric Henry reaction between different aldehydes and nitromethane, and the desired products have been obtained with high chemical yields (up to 99%) and high enantiomeric excess (up to 93%). The optimized catalyst promoted the diastereoselective Henry reaction of various aldehyde substrates and nitroalkane, which gave the corresponding anti‐selective adduct with up to 99% yield and 83:17 anti/syn selectivity. Upon scaling up to gram quantities, the β‐nitroalcohol was obtained in good yield (96%) with excellent selectivities (93% ee). The chiral induction mechanism was tentatively explained on the basis of a previously proposed transition‐state model. Copyright © 2014 John Wiley & Sons, Ltd.     

Asymmetric Allylation of Ketones and Subsequent Tandem Reactions Catalyzed by a Novel Polymer‐Supported Titanium–BINOLate Complex

By using a novel, simple, and convenient synthetic route, enantiopure 6‐ethynyl‐BINOL (BINOL=1,1‐binaphthol) was synthesized and anchored to an azidomethylpolystyrene resin through a copper‐catalyzed alkyne–azide cycloaddition (CuAAC) reaction. The polystyrene (PS)‐supported BINOL ligand was converted into its diisopropoxytitanium derivative in situ and used as a heterogeneous catalyst in the asymmetric allylation of ketones. The catalyst showed good activity and excellent enantioselectivity, typically matching the results obtained in the corresponding homogeneous reaction. The allylation reaction mixture could be submitted to epoxidation by simple treatment with tert‐butyl hydroperoxide (TBHP), and the tandem asymmetric allylation epoxidation process led to a highly enantioenriched epoxy alcohol with two adjacent quaternary centers as a single diastereomer. A tandem asymmetric allylation/Pauson–Khand reaction was also performed, involving simple treatment of the allylation reaction mixture with Co₂(CO)₈/N‐methyl morpholine N‐oxide. This cascade process resulted in the formation of two diastereomeric tricyclic enones in high yields and enantioselectivities.     

Asymmetric Synthesis of Hydrocarbazoles Catalyzed by an Octahedral Chiral‐at‐Rhodium Lewis Acid

A bis‐cyclometalated chiral‐at‐metal rhodium complex catalyzes the Diels–Alder reaction between N‐Boc‐protected 3‐vinylindoles (Boc=tert‐butyloxycarbonyl) and β‐carboxylic ester‐substituted α,β‐unsaturated 2‐acyl imidazoles with good‐to‐excellent regioselectivity (up to 99:1) and excellent diastereoselectivity (>50:1 d.r.) as well as enantioselectivity (92–99 % ee) under optimized conditions. The rhodium catalyst serves as a chiral Lewis acid to activate the 2‐acyl imidazole dienophile by two‐point binding and overrules the preferred regioselectivity of the uncatalyzed reaction.