Catalytic Asymmetric Five‐Component Tandem Reaction: Diastereo‐ and Enantioselective Synthesis of Densely Functionalized Tetrahydropyridines with Biological Importance

The first catalytic asymmetric five‐component tandem reactions of β‐keto esters, aromatic aldehydes and anilines have been established in the presence of a chiral phosphoric acid, affording densely functionalized tetrahydropyridines with concomitant generation of five σ bonds and two stereogenic centers in high diastereo‐ and enantioselectivities (up to >99:1 dr, 95:5 er). In addition, the first isolation and preparation of a diene species as the key intermediate of the reaction has been successfully realized, leading to the formation of the desired tetrahydropyridine via further condensation with in situ generated imine, which supported the proposed tandem [4+2] reaction pathway to some extent. This protocol not only represents the first enantioselective example of this five‐component tandem reaction, but also provides an unprecedented access to enantioenriched tetrahydropyridines with structural diversity, which holds great potential in medicinal chemistry.     

Highly Enantioselective Biginelli Reaction Promoted by Chiral Bifunctional Primary Amine‐Thiourea Catalysts: Asymmetric Synthesis of Dihydropyrimidines

The diastereospecific formation of dihydropyrimidines (DHPMs) has been achieved in moderate to high yields with up to 99% ee by a Biginelli reaction. The reaction was performed by using a combined catalyst consisting of a chiral bifunctional primary amine‐thiourea 9f and a Brønsted acid with tert‐butylammonium trifluoroacetate (t‐BuNH₂⋅TFA) as additive in dichloromethane at room temperature. The possible mechanism for the reaction has been proposed to explain the origin of the activation and the asymmetric induction.     

Combination of Enantioselective Metal Catalysis and Organocatalysis: Enantioselective Sequential Hydroformylation/ Aldol Reactions

This work reports the possibility of controlling the sense of enantio‐ and diastereoinductions in the sequential hydroformylation and aldol reactions via the judicious combination of a chiral metal catalyst with a chiral organocatalyst. The diastereoselectivity of the reaction between styrene, syngas and acetone can be increased by using a matched pair of catalysts, [rhodium/(2S,4S)‐Chiraphite]/(S)‐organocatalyst and decreased, but not inverted, by using a mismatched pair of catalysts, [rhodium/(2R,4R)‐Chiraphite]/(S)‐organocatalyst.     

An Enantioselective Cascade Cyclopropanation Reaction Catalyzed by Rhodium(I): Asymmetric Synthesis of Vinylcyclopropanes

N‐Tosylhydrazone‐yne‐ene substrates are satisfactorily prepared and their cyclization under rhodium catalysis is evaluated. A cascade process involving rhodium vinyl carbene formation – through carbene/alkyne metathesis – and cyclopropanation has been developed to stereoselectively afford vinylcyclopropanes.

     

Asymmetric Counteranion‐Directed Iron Catalysis: A Highly Enantioselective Sulfoxidation

A highly active and enantioselective ion‐pair sulfoxidation catalyst, consisting of an achiral iron(III)‐salen cation and a chiral phosphate counteranion, mediates the oxidization of various sulfides with high yields and enantioselectivities. The enantioselectivities observed, especially for electron‐poor substrates, represent the best results so far in manganese and iron‐salen systems. This work represents the first application of our concept of asymmetric counteranion‐directed catalysis (ACDC) to iron catalysis.     

Asymmetric Heterogeneous Catalysis: Science and Engineering

Asymmetric heterogeneous catalysis is a vivid branch of catalysis, remaining, however, largely a domain of organic chemists. The view towards asymmetric heterogeneous catalysis adopted in this review is mainly from catalytic science and engineering. Not only reaction mechanisms, but also catalytic properties, kinetic regularities, as well as chemical engineering aspects, are covered with the main focus on recent developments.     

Asymmetric Heterogeneous Catalysis: Science and Engineering

Asymmetric heterogeneous catalysis is a vivid branch of catalysis, remaining, however, largely a domain of organic chemists. The view towards asymmetric heterogeneous catalysis adopted in this review is mainly from catalytic science and engineering. Not only reaction mechanisms, but also catalytic properties, kinetic regularities, as well as chemical engineering aspects, are covered with the main focus on recent developments.     

Geminal Bis(sulfoximine)s: Synthesis and Applications in Asymmetric Catalysis

A number of C₂‐symmetrical geminal bis(sulfoximine)s have been prepared for the first time and used as ligands in boron‐mediated reductions of acetophenone and copper complex‐catalyzed 1,4‐additions of diethylzinc to 2‐cyclohexenone. The copper complex of bis(sulfoximine) 46 was found to be highly active in this type of reaction, furnishing the addition product in nearly quantitative yield even at −90 °C. From the reaction of bis(sulfoximine) 42 with Cu(OTf)₂ a copper complex was isolated and characterized by X‐ray structural analysis. A mixture of SES‐Cl and NaN₃ in acetonitrile was found to behave like SES‐N₃ in FeCl₂‐mediated iminations of sulfoxides, affording the corresponding sulfoximines with complete retention of the sulfur configuration.     

Enantioselective Lewis‐Base‐Catalyzed Asymmetric Hydrosilylation of Substituted Benzophenone N‐Aryl Imines: Efficient Synthesis of Chiral (Diarylmethyl)amines

Lewis‐base‐catalyzed asymmetric hydrosilylation of substituted benzophenone N‐aryl imines was investigated. Among various chiral Lewis‐base catalysts, a catalyst derived from L ‐Serine was found to be the most favorable one which promote the reaction to afford a series of (diarylmethyl)amines with high yields (up to 97 %) in moderate to good enantioselectivities (up to 97 % ee). The absolute configuration of the product was determined by the X‐ray crystallographic analysis.

     

Squaramide‐Catalyzed Enantioselective Cascade Approach to Bispirooxindoles with Multiple Stereocenters

A bifunctional squaramide‐catalyzed Michael/Michael cascade reaction for the construction of spirotetrahydrofuran bispirooxindoles was developed. The products were obtained in moderate to excellent yields with excellent diastereo‐ and enantioselectivities (up to >20:1 dr, >99% ee). This straightforward process serves as a powerful method for the enantioselective construction of potentially bioactive bispirooxindoles in which two of the four contiguous chiral centers are spiro all‐carbon quaternary centers on a single tetrahydrofuran ring. Meanwhile, the synthetic practicality of this methodology was illustrated by performing the reaction on a gram‐scale with the same efficiency and stereoselectivity.

     

N‐Heterocyclic Carbene‐Mediated Enantioselective Addition of Phenols to Unsymmetrical Alkylarylketenes

Chiral N‐heterocyclic carbenes (NHCs) mediate the enantioselective addition of 2‐phenylphenol to unsymmetrical alkylarylketenes, delivering α‐alkyl‐α‐arylacetic acid derivatives with good levels of enantiocontrol (up to 84% ee). Enantiodivergent stereochemical outcomes are observed using 2‐phenylphenol and benzhydrol in the NHC‐promoted esterification reaction using a triazolium precatalyst derived from pyroglutamic acid, consistent with distinct mechanistic pathways operating within these processes.     

Synthesis of Chiral Polyethers Containing Imidazolidinone Repeating Units and Application as Catalyst in Asymmetric Diels–Alder Reaction

In this study, enantiopure imidazolidinones containing two hydroxyphenyl groups were synthesized, and the Williamson synthesis of the chiral bisphenols thus prepared with dihalides afforded polyethers containing chiral imidazolidinone repeating units. These chiral imidazolidinone polyethers exhibited excellent catalytic activity in the asymmetric Diels–Alder reaction. With the use of these polymeric catalysts, enantioselectivities up to 99% were obtained, higher than those obtained by the corresponding monomeric imidazolidinone catalyst in homogeneous solution. The polymeric catalysts were found to be insoluble in commonly used organic solvents, and they could be repeatedly used without the loss of activity.

     

Linked‐BINOL: An Approach towards Practical Asymmetric Multifunctional Catalysis

The development and application of a novel linked‐1,1′‐binaphthol (linked‐BINOL) as an approach towards practical asymmetric multifunctional catalysis is described. Linked‐BINOL was first designed to increase the stability of a Ga‐Li‐BINOL complex against ligand exchange with 4‐methoxyphenol. An oxygen‐containing linked‐BINOL, which is a semi crown ether, was effective in both promoting the formation of a monomer complex and increasing the stability of the Ga‐Li complex. A Ga‐Li‐linked‐BINOL complex promoted the epoxide opening reaction in up to 96% enantiomeric excess (ee). Second, based on the X‐ray structural information of the Ga‐Li‐linked‐BINOL complex, we designed a more stable lanthanide linked‐BINOL complex. An air‐stable, storable, and reusable La‐linked‐BINOL complex promoted the Michael reaction in up to >99% ee. The catalyst activity remained unchanged after storage under air for 4 weeks. Calculations suggested that the linked‐BINOL would function as a pentadentate ligand in a lanthanum complex, thus efficiently improving the stability of the complex. Finally, the linked‐BINOL was applied to a new homobimetallic multifunctional catalysis. A dinuclear Zn‐Zn‐linked‐BINOL complex promoted the enantio‐ and diastereoselective direct aldol reaction in up to 99% ee, where one Zn cation might function as a Lewis acid and the other Zn‐phenoxide as a Brønsted base.     

Synthesis of Chiral Cyclopropyl Carbocyclic Purine Nucleosides via Asymmetric Intramolecular Cyclopropanations Catalyzed by a Chiral Ruthenium(II) Complex

The synthesis of chiral cyclopropyl carbocyclic purine nucleoside analogues via the highly enantioselective intramolecular cyclopropanation reactions has been reported. With a chiral ruthenium(II)‐phenyloxazoline complex as the catalyst, cyclopropyl carbocyclic purine nucleoside analogues containing three contiguous stereocenters were obtained with up to 99% yield and 99% ee. Furthermore, a chiral cyclopropyl carbocyclic adenosine nucleoside having anti‐BLV activity could be synthesized in a concise manner using this strategy.

     

Recyclable Enantioselective Catalysts Based on Copper(II) Complexes of 2‐(Pyridine‐2‐yl)imidazolidine‐4‐thione: Their Application in Asymmetric Henry Reactions

This paper describes the preparation of enantioselective catalysts based on derivatives of imidazolidine‐4‐thione and their subsequent anchoring by means of a sulfur atom on a polymeric carrier. First, we verified the catalytic activity and enantioselectivity in the Henry reaction of the homogeneous variants of the catalysts, i.e., the copper(II) complexes of 2‐(pyridine‐2‐yl)imidazolidine‐4‐thiones and 4‐benzylsufanyl‐2‐(pyridine‐2‐yl)imidazolines themselves. It was found that these catalysts exhibit high enantioselectivity (up to 98% ee). Subsequently, the imidazolidine‐4‐thione catalysts were immobilized by anchoring to polymeric carriers based on a copolymer of styrene and 4‐vinylbenzyl chloride. These heterogeneous catalysts were analogously tested with regard to their catalytic activity and enantioselectivity in the Henry reaction, and moreover, the possibility of their separation and reuse was studied. It was found that all the prepared immobilized catalysts are highly enantioselective (up to 97% ee). Their recycling ability was tested in Henry reaction of 2‐methoxybenzaldehyde with nitromethane. It was found that they can be recycled more than ten times without any decrease of their enantioselectivity. Therefore, they present a better means of catalysis than the original copper(II) complexes of imidazolidine‐4‐ones from both economic as well as ecological points of view. Thus, such immobilized catalysts exhibit high application potential for the asymmetric Henry reaction.

     

Organo‐ and Iron(0) Catalysis for an Enantioselective Michael Addition–Hemiketalization–Fragmentation Sequence to Protected ω‐Hydroxy‐nitroketones

By combining an organocatalyzed Michael addition of 1,3‐diketones to hydroxy‐nitroolefins with a subsequent, innovative iron(0)‐catalyzed fragmentation, key enantioenriched ketones possessing additional nitro and protected alcohol functions could efficiently be prepared under excellent enantiocontrol (typically 95% ee). The reaction was made possible by the discovery that photochemical activation of iron pentacarbonyl [Fe(CO)₅], a cheap widely available complex, efficiently catalyzed a Claisen‐type fragmentation under mild conditions, avoiding decomposition of the intermediates and products.

     

Pd(PPh3)4催化Suzuki偶联反应合成4-溴-2-氟-联苯

以苯硼酸和2-氟-4-溴碘苯为起始原料,经Suzuki偶联反应合成了色谱纯度99.5%以上的医药和液晶中间体4-溴-2-氟-联苯,目标化合物进行了1HNMR、IR和GC-MS表征。结果表明,反应体系中氧气的存在是导致硼酸自偶副产物产生的主要原因;Pd(PPh3)4催化剂及过量的苯硼酸均会导致三联苯副产物的产生。     

Enantioselective Gold(I) Catalysis with Chiral Monodentate Ligands

Enantioselective gold(I) catalysis is receiving a growing level of credit in the field of asymmetric synthesis. After a pioneering work in the mid-1980s the area remained almost silent for several years, until densely substituted diphosphine chiral ligands were disclosed as competent chiral units for gold-catalyzed stereoselective manipulation of unactivated unsaturated hydrocarbons. The chemistry of alkynes, allenes and most recently also alkenes received significant benefits from the latter developments. More recently, ad hoc designed chiral monodentate ligands have risen to prominence in producing robust, highly tunable (electronic and steric) and efficient chiral cationic mononuclear gold species for asymmetric transformations. In this scenario, electron-deficient phosphorus-based (i.e., phosphoramidites, phosphites) but also axially chiral electron-rich carbene ligands deserve particular mention and the corresponding applications will be summarized herein.     

New Developments in Advanced Synthesis & Catalysis: Growth and High‐Impact Research for Green Organic Synthesis

Advanced Synthesis & Catalysis has continued on the upward curve in 2011 and passed several milestones along the way. The submissions exceeded 1000, the number of printed pages reached 3500, and the number of published articles passed the 400 mark. With 2010 impact factors of 5.25 (2‐year IF) and 5.36 (5‐year IF) ASC continued to be at the top for green synthesis. Submissions and published papers from Europe and from Asia continue to dominate. Over one quarter of the published papers now come from China and Hong Kong. The percentage of communications continued to grow and is now 54% of the published articles. The new Editorial and Advisory Boards have settled in and with them Advanced Synthesis & Catalysis will further change and develop over the next years. The goal of Advanced Synthesis & Catalysis continues to be to publish seminal research as chemists move toward greener synthesis: “new catalytic systems effecting perfect chemical reactions that give only the desired products, with 100% selectivity and 100% yield without unwanted wastes.”     

N-硝基苯基脯氨酰胺小分子催化剂的合成及其在环己酮与硝基烯烃不对称Michael加成中的应用

以苄氧羰基保护的L-脯氨酸和硝基苯胺类化合物为起始原料,通过酰胺化反应和脱苄氧羰基反应,合成了两个结构新颖的N-硝基苯基脯氨酰胺类催化剂,其结构经~~1HNMR、~(13)CNMR和HR-ESI-MS确证。该类催化剂用于环己酮与硝基烯烃的不对称Michael加成反应,其中化合物(S)-N-(2-甲氧基-4-硝基苯基)脯氨酰胺催化所得产物具有优异的收率(82%)、较高的非对映体比例(94∶6 dr)和一定的对映选择性(21%e.e.)。