Asymmetric 1,4‐Addition of Diethylzinc to Cyclic Enones Catalyzed by Cu(I)‐Chiral Sulfonamide‐Thiophosphoramide Ligands and Lithium Salts

The chiral sulfonamide‐thiophosphoramide ligand L1 , prepared from the reaction of (1R,2R)‐(−)‐1,2‐cyclohexanediamine with diphenylthiophosphoryl chloride and p‐toluenesulfonyl chloride, was used as a chiral ligand in Cu(MeCN)₄ClO₄‐promoted catalytic asymmetric addition of diethylzinc to cyclic enones using LiCl as an additive in which up to 90% ee can be realized under mild conditions within 0.5 h. This chiral ligand is stable and recoverable after usual work‐up and can be reused in the same catalytic asymmetric reaction. Moreover, it was found that this series of chiral ligands represents a type of S,O‐bidentate ligands on the basis of ¹H NMR, ³¹P NMR and ¹³C NMR spectroscopic investigations. The linear effect of ligand ee and product ee further revealed that the active species is a monomeric Cu(I) complex bearing a single ligand.     

Rhodium‐BisbenzodioxanPhos Complex‐Catalyzed Homogeneous Enantioselective Pauson–Khand‐Type Cyclization in Alcoholic Solvents

The chiral atropisomeric diphosphane ligand (S)‐BisbenzodioxanPhos was found to be highly effective in the co‐operative processeses of aldehyde decarbonylation and cascaded enantioselective Pauson–Khand‐type reactions. Various 1,6‐enynes were transformed to the corresponding bicyclic cyclopentenones in good yields and enantiomeric excesses (up to 96% ee). The attractive feature of this new Rh‐catalyzed homogeneous dual catalysis system is that the reaction can be performed in alcoholic solution.     

Chiral Dirhodium(II) Carboxamidate‐Catalyzed [2+2]‐Cycloaddition of TMS‐Ketene and Ethyl Glyoxylate

The [2+2]‐cycloaddition reaction between ethyl glyoxylate and trimethylsilylketene is reported. Enantiomeric excesses up to 83% have been achieved with the use of only 1.0 mol % of a previously unreported chiral imidazolidinone‐ligated dirhodium(II) carboxamidate catalyst. An extensive survey of chiral catalysts has shown that enantiocontrol for cycloaddition increases as the steric bulk of the ligand is increased. However, enantioselectivity is increased to 99% ee by the addition of 10 mol % of quinine as a co‐catalyst with a chiral dirhodium(II) azetidinone‐ligated catalyst, and there is a significant decrease in reaction time.     

Catalytic Asymmetric Mannich‐Type Reactions Using a Novel Chiral Iron Complex

Catalytic asymmetric Mannich‐type reactions using a novel chiral iron complex have been developed. The reactions proceeded smoothly in the presence of a catalyst prepared from iron(II) chloride, a BINOL derivative, and i‐Pr₂NEt. The desired products were obtained in good yield with good to high enantioselectivity, when 3,3′‐I₂BINOL was employed as a chiral ligand. A protic additive such as methanol facilitated the reactions effectively.     

Phosphoramidite Ligands Based on Simple 1,2‐Diols: Synthesis,Use in Copper‐Catalyzed Asymmetric Additions,and Achirotopic Stereogenic Phosphorus Centres

Phosphoramidite ligands are widely used in catalysis and normally constructed from large C₂‐symmetrical diols such as BINOL or TADDOL. We report here on new ligands based on a set of simple diols that had been previously overlooked. Ligands based on (S,S)‐trans‐cyclohexanediol and (R,R)‐(+)‐1,2‐diphenyl‐1,2‐ethanediol, in combination with both chiral and achiral amines, were tested in 3 different copper‐catalyzed asymmetric reactions and up to 89% ee was observed. A different ligand gave the best results in each reaction examined. Using meso‐cis‐cyclohexanediol and meso‐cis‐diphenyl‐1,2‐ethanediol with a chiral non‐racemic amine gave diastereomeric ligands bearing achirotopic stereogenic phosphorus atoms which were characterized with the assistance of X‐ray crystallography and variable temperature NMR studies. This work provides a new set of ligands that may be useful in some asymmetric reactions when phosphoramidites based on BINOL and TADDOL are ineffective. We also identify a novel stereochemical feature of phosphoramidites that may be useful in asymmetric catalysis and ligand design.

     

Ferrocene‐Based Chiral Phosphine‐Triazines: A New Family of Highly Efficient P,N Ligands for Asymmetric Catalysis

The presence of the additional heterocyclic nitrogen atoms in chiral P,N ligands has an important influence on the asymmetric catalysis, and a clear trend was observed in the present research that the enantioselectivity and reactivity were significantly increased by raising the number of heterocyclic nitrogen atoms in these P,N ligands. Through finely tuning the number of heterocyclic nitrogen atoms, a new family of ferrocene‐based chiral phosphine‐triazine ligands with three heterocyclic nitrogen atoms has been developed and successfully applied in Pd‐catalyzed asymmetric allylic substitution. Up to 99% ee with 99% yield of allylic alkylation products and 94% ee of allylic amination products have been obtained by the use of ligand (R_c,S_p)‐ 1f with a 4,6‐diphenoxy‐1,3,5‐triazine moiety.     

Kinetic resolution of terminal epoxides with phenols promoted by heterometallic Co–Al and Co–Ga salen complexes

The binuclear chiral (salen) Co complexes bearing Lewis acid salt (Al and Ga) and 4-nitrobenzene sulfonic acid (NBS) catalyze the enantioselective ring opening of terminal epoxides with phenol derivatives. The easily prepared complexes exhibited very high catalytic reactivity and enantioselectivity for the asymmetric ring opening of terminal epoxides with phenol and consequently provide enantiomerically enriched corresponding α-aryloxy alcohols (up to >99% ee). The two unit of salen complexes combined by Lewis acid exhibited co-operative catalysis during the ring opening reaction.     

C3‐Symmetric Titanium(IV) Triphenolate Amino Complexes for a Fast and Effective Oxidation of Secondary Amines to Nitrones with Hydrogen Peroxide

The efficient catalytic oxidation of secondary amines to nitrones using hydrogen peroxide as primary oxidant is described. The titanium(IV) complex 2 bearing a C₃‐symmetrical triphenolate amino ligand has proved to be an air‐ and water‐tolerant complex that efficiently catalyzes secondary amine oxidations at 60 °C without previous activation [catalyst loading as low as 0.01%, yields up to 99%, turnover numbers (TONs) up to 8000 and turnover frequencies (TOFs) up to 11000 h⁻¹).     

Charge‐Transfer Interactions: An Efficient Tool for Recycling Bis(oxazoline)‐Copper Complexes in Asymmetric Henry Reactions

An anthracenyl‐modified chiral bis(oxazoline) copper complex has been demonstrated to efficiently promote nitroaldol reactions between structurally varying aldehydes and nitromethane or nitroethane. The catalyst was recovered through formation of a charge transfer complex between the chiral ligand and trinitrofluorenone and its subsequent precipitation with pentane. The efficiency of this procedure was proved through several consecutive catalytic cycles that allowed the sturdy formation of the expected product with a high enantioselectivity. The catalyst′s stability was also put to the test in an original multi‐substrate procedure. Following the same recovery concept, a new heterogeneous procedure was tested for which trinitrofluorenone was covalently linked to a silica support. Asymmetric heterogeneous catalysis was performed under these conditions as one of the few examples demonstrating the potential catalyst recycling in nitroaldol reactions through reversible, non‐covalent interactions.     

(Cyclopentadienyl)ruthenium‐Catalyzed Regio‐ and Enantioselective Decarboxylative Allylic Etherification of Allyl Aryl and Alkyl Carbonates

(Cyclopentadienyl)tris(acetonitrile)ruthenium hexafluorophosphate {[CpRu(NCMe)₃][PF₆]} or (cyclopentadienyl)(η⁶‐naphthalene)ruthenium hexafluorophosphate {[CpRu(η⁶‐naphthalene)][PF₆]} in combination with a pyridine oxazoline ligand efficiently catalyze the decarboxylative allylic rearrangement of allyl aryl carbonates. Good levels of regio‐ and enantioselectivity are obtained. Starting from enantioenriched secondary carbonates, the reaction is stereospecific and the corresponding allylic ethers are obtained with net retention of configuration. An intermolecular version of this transformation was also developed using allyl alkyl carbonates as substrates. Conditions were found to obtain the corresponding products with similar selectivity as in the intramolecular process. Through the use of a hemi‐labile hexacoordinated phosphate counterion, a zwitterionic air‐ and moisture‐stable chiral ruthenium complex was synthesized and used in the enantioselective etherification reactions. This highly lipophilic metal complex can be recovered and efficiently reused in subsequent catalysis runs.     

MaxPHOS Ligand: PH/NH Tautomerism and Rhodium‐ Catalyzed Asymmetric Hydrogenations

MaxPHOS is an active and robust P‐stereogenic ligand for asymmetric catalysis. The presence of an  NH bridge between the two phosphine moieties allows the NH/PH tautomerism to take place. The neutral ligand, in which the NH form predominates, is an air‐sensitive compound. However, protonation of MaxPHOS leads to the stable PH form of the ligand, in which the overall positive charge is distributed on both P centers. This protonation turns the MaxPHOS⋅HBF₄ salt 3 into an air‐stable compound both in the solid state and in solution. The salt 3 is also a convenient precursor for the preparation of rhodium(I) complexes by direct ligand exchange with the complex [Rh(acac)(cod)]. Finally, the corresponding rhodium(I)‐MaxPHOS complex was tested in the asymmetric hydrogenation of a wide range of substrates. The complex proved to be a highly selective and robust system in these reactions.

     

Aqueous Asymmetric Mukaiyama Aldol Reaction Catalyzed by Chiral Gallium Lewis Acid with Trost‐Type Semi‐Crown Ligands

The combination of Ga(OTf)₃ with chiral semi‐crown ligands ( 1a – e ) generates highly effective chiral gallium Lewis acid catalysts for aqueous asymmetric aldol reactions of aromatic silyl enol ethers with aldehydes. A ligand‐acceleration effect was observed. Water is essential for obtaining high diastereoselectivity and enantioselectivity. The p‐phenyl substituent in aromatic silyl enol ether ( 2 h ) plays an important role and increases the enantioselectivity up to 95% ee. Although aliphatic silyl enol ethers provided low enantioselectivities and silylketene acetal is easily hydrolyzed in aqueous alcohol, the aldol reactions of silylketene thioacetal ( 12 ) with aldehydes in the presence of gallium‐Lewis acid catalysts give the β‐hydroxy thioester with reasonable yields and high diastereo‐ (up to 99 : 1) and enantioselectivities (up to 96% ee).     

Highly Efficient Asymmetric Three‐Component Vinylogous Mannich Reaction Catalyzed by a Chiral Scandium(III)‐ N,N′‐Dioxide Complex

The asymmetric three‐component vinylogous Mannich reaction of an acyclic silyl dienol ester, an aldehyde and 2‐aminophenol was accomplished using a chiral N,N′‐dioxide‐scandium(III) complex as the catalyst. A variety of aldehydes were found to be suitable substrates for the reaction and the desired δ‐amino‐α,β‐unsaturated esters were obtained in 90–99% yields with good to excellent enantioselectivities (up to >99% ee) and complete regioselectivities. Moreover, the simple experimental procedures were air‐tolerant and convenient. The present catalytic process provides the potential for large‐scale syntheses of the chiral δ‐amino‐α,β‐unsaturated esters.     

Rhodium/MonoPhos‐Catalysed Asymmetric Hydrogenation of Enamides

The monodentate phosphoramidite MonoPhos has been used in the rhodium‐catalysed asymmetric hydrogenation of N‐acetyl‐α‐arylenamides. This ligand is readily available via a one‐step procedure and is air stable. Its Rh(I) complex, which is an effective catalyst precursor for the hydrogenation of dehydroamino acids, also gives high enantioselectivities for this class of substrates. Because of the facile synthesis and stability of MonoPhos, its complex provides a general solution in preparing chiral amine derivatives through asymmetric hydrogenation.     

Efficient and Selective Rhodium‐Catalyzed Hydrophosphorylation of Dienes

The hydrophosphorylation of a model 1,6‐diene having a terminal and an internal alkene function has been investigated. Free radical protocols lead invariably to mixtures of cyclic phosphonate products, due to rapid cyclization of the intermediary radical species. Rhodium catalysis using a cyclic pinacol‐derived phosphonate provides an efficient technique for the highly selective (>99 %) hydrophosphorylation at the terminal alkene function. In situ modification of Wilkinson’s complex by addition of 2–50 equivalents (vs. Rh) of a monophosphine (PCy₃>PPh₃) or carbene ligand greatly improves the catalyst performances (TON up to 2250 mol phosphonate/mol Rh). An even more efficient system was obtained with 2 equivalents (vs. Rh) of the bidentate 1,6‐bis(diphenylphosphino)hexane ligand, which affords so far unprecedented high catalytic productivity (TON up to 4 550 mol phosphonate/mol Rh) and activity (TOF up to 250 h⁻¹).     

含有联二萘结构手性负载催化剂用于不对称催化反应研究进展

不对称催化是获得单一光学活性化合物最好的方法之一,然而贵重的手性催化剂的分离与回收是一个难题,针对BINOL、BINAP这两类具有联二萘结构的手性负载催化剂近年的研究进行了总结,认为以结构可控的高分子为载体,发展从分子水平上设计高分子手性配体及催化剂的方法是可行的。     

Storable and Air‐Stable Zirconium Complex‐Catalyzed Highly Enantioselective Darzens Reaction of Diazoacetamide with Aldehydes

An asymmetric Darzens reaction of aldehydes with diazo‐N,N‐dimethylacetamide ( 3 ) catalyzd by an air‐stable and storable chiral zirconium Lewis acid catalyst, which is formed from 3,3′‐diiodobinaphthol and tetrabutoxyzirconium, gives solely the cis‐glycidic amides in high yields with excellent enantioselectivity (up to 97% yield, >99% ee).     

Vanadium‐Catalyzed Enantioselective Sulfoxidation and Concomitant,Highly Efficient Kinetic Resolution Provide High Enantioselectivity and Acceptable Yields of Sulfoxides

Simple, inexpensive, preformed vanadium‐Schiff base complexes were facilely prepared and used in enantioselective sulfoxidation. Both the amount of aqueous H₂O₂ and reaction time greatly influenced the ee values and yields of chiral sulfoxides. High enantioselectivities (up to 99% ee) and reasonable yields (>40%) for various chiral sulfoxides were achieved by combining enantioselective sulfoxidation and appropriate concomitant kinetic resolution.     

Probing the Mechanism of the Asymmetric Aminolysis of meso‐Epoxides Catalyzed by a Proline‐Based N,N′‐Dioxide‐Indium Tris(triflate) Complex

An exploration of the mechanism of the aminolysis of meso‐epoxides catalyzed by the proline‐based N,N′‐dioxide‐indium tris(triflate) complex was performed using control experiments, UV‐Vis spectroscopy, ¹H NMR, electrospray ionization mass spectrometry (ESI‐MS) and scanning electron microscopy (SEM). Control experiments disclosed that the ligand‐to‐indium tris(triflate) ratio, the catalyst loading, the concentration, and the presence of 4 Å MS have dramatic effects on this reaction with regard to both the yield and the enantioselectivity. Combined with control experiments, UV‐Vis spectroscopy, ¹H NMR, ESI‐MS and SEM analyses revealed that molecular sieves perform multiple functions in the catalysis. A plausible molecular sieves‐assisted reaction pathway was proposed. In this pathway, molecular sieves perform (i) as desiccant to in situ dry the reaction system, (ii) as proton transfer agent to accelerate the catalysis, and (iii) as counter ion source to preserve the electroneutrality of the transition states. Besides, the generality of the substrate scope was further explored; excellent yields (up to 99%) and enantioselectivities (up to 99% ee) were obtained.     

Synthesis of Substituted Mandelic Acid Derivatives via Enantioselective Hydrogenation: Homogeneous versus Heterogeneous Catalysis

An extensive screening of both homogeneous and heterogeneous catalysts was carried out for the enantioselective hydrogenation of p‐chlorophenylglyoxylic acid derivatives. For p‐chlorophenylglyoxylic amides only homogeneous Rh‐diphosphine complexes gave satisfactory results, ees up to 87% were observed for the cy‐oxo‐pronop ligand. For methyl p‐chlorophenylglyoxylate both a homogeneous as well as a heterogeneous catalyst performed with ees >90%. A Pt catalyst modified with cinchona derivatives achieved 93% ee for the (R)‐ and 87% ee for the (S)‐methyl p‐chloromandelate. A Ru‐MeObiphep catalyst also reached 93% ee with TONs up to 4000 and TOFs up to 210 h⁻¹. For all catalytic systems the effects of the metal, the nature of the chiral auxiliary and the solvent as well as of the reaction conditions were investigated. The homogeneous process was scaled up to the kg scale and the enantiomeric purity of the product was enhanced to >99% ee by two recrystallizations of the free p‐chlorophenylmandelic acid.