An Unprecedented Rhodium‐Catalyzed Asymmetric Intermolecular Hydroacylation Reaction with Salicylaldehydes

An unprecedented enantio‐ and diastereoselective rhodium‐catalyzed intermolecular hydroacylation reaction of salicylaldehydes with norbornenes is reported in which the corresponding aryl ketones are obtained in high diastereomeric and moderate enantiomeric excesses. It was found that monodentate phosphoramidite ligands gave rise to endo products, while bidentate phosphine ligands catalyzed the reaction to form exo products predominantly.     

Ligand Control in Enantioselective Desymmetrization of Bicyclic Hydrazines: Rhodium(I)‐Catalyzed Ring‐Opening versus Hydroarylation

The efficient desymmetrization of 2,3‐bicyclic hydrazines with boronic acids through rhodium‐catalyzed ring‐opening or reductive arylation is described. Excellent levels of enantioselectivity are achieved in ring‐opening with ortho‐substituted boronic acids, using Josiphos‐type ligands. Alternatively, reductive arylation occurs selectively with electron‐poor Josiphos and Walphos ligands. A C H activation/1,4‐migration mechanism was established through deuterium transfer experiments.     

Asymmetric Intramolecular C?H Insertion of α‐Diazoacetamides in Water by Dirhodium(II) Catalysts Derived from Natural Amino Acids

The asymmetric dirhodium(II)‐catalyzed intramolecular C H insertion of α‐diazo acetamides in water is described for the first time. The use of natural α‐amino acids as chiral ligands allowed the preparation of novel dirhodium(II) homochiral complexes by a simple procedure consisting of the in situ ligand exchange starting from dirhodium tetraacetate. The catalytic system was further reused up to 7 cycles and β‐lactams were obtained in good yields and enantiomeric excess.     

The Complex Synergy of Water in Metal/Bromide Autoxidations. Part II. Effect of Water and Catalyst on the Aerobic Oxidation of Benzaldehydes and the Effect of Water on the Elementary Catalytic Pathways

All of the rates of the elementary steps in the Co/Br and Co/Mn/Br homogeneous, liquid‐phase catalyzed reactions decrease with increasing water concentration in acetic acid. The step‐wise replacement of the acetic acid ligands by water ligands in the coordination sphere of the catalyst metals may be responsible for this behavior. The non‐catalyzed and metal‐catalyzed (Co, Co/Mn/Br and Co/Mn) aerobic oxidations of benzaldehyde and 4‐methylbenzaldehyde are reported. The non‐catalyzed autoxidations are quite vigorous reactions in acetic acid/water mixtures but by‐products from the Baeyer–Villiger reaction, the thermal decomposition of the peroxy acid, and over‐oxidation to carbon dioxide limit the yield to the aromatic carboxylic acids. As the concentration of a Co or Co/Mn/Br catalyst increases these by‐products are first reduced and then eliminated probably due to the very fast, selective reaction of [Co(II)]₂ with the peroxy acid. A Co/Mn catalyst completely inhibits the autoxidation of the benzaldehydes. There is a gradual change in the yield of terephthaldicarboxaldehyde from 4‐methylbenzaldehyde with increasing Co/Mn/Br concentration suggesting that the non‐catalyzed steps are being replaced by catalyzed ones. The autoxidation of heptaldehyde generates about 500 times more carbon monoxide than does benzaldehyde using a Co/Mn/Br catalyst and gives only a 50% yield to heptanoic acid consistent with excessive amounts of decarbonylation with aliphatic aldehydes.     

Iron‐Catalyzed C?N Cross‐Coupling of Sulfoximines with Aryl Iodides

An inexpensive and experimentally simple, iron‐catalyzed N‐arylation reaction of NH‐sulfoximines with aryl iodides is reported. This complementary method to the known palladium‐ and copper‐catalyzed ones features the use of a combination of environmentally friendly FeCl₃ and N,N′‐dimethylethylenediamine (DMEDA) as catalytic system and allows the efficient preparation of various N‐arylsulfoximines in high yields.     

One Step Synthesis of Chiral Olefins via Asymmetric Diamination and their Applications as Ligands for Rhodium(I)‐Catalyzed 1,4‐Additions

A variety of acyclic chiral dienes were synthesized in a single step via palladium(0)‐catalyzed asymmetric allylic and homoallylic C H diamination of terminal olefins. The applications of such simple dienes as steering ligands for rhodium(I)‐catalyzed asymmetric 1,4‐additions afforded the corresponding adducts in excellent yields and up to 85% ee.     

Modular Furanoside Phosphite‐Phosphoroamidites,a Readily Available Ligand Library for Asymmetric Palladium‐Catalyzed Allylic Substitution Reactions. Origin of Enantioselectivity

A library of furanoside phosphite‐phosphoroamidite ligands has been synthesized and screened in the palladium‐catalyzed allylic substitution reactions of several substrate types. These series of ligands can be prepared efficiently from easily accessible D ‐xylose and D ‐glucose. Their modular nature enables the position of the phosphoroamidite group, configuration of C‐3 of the furanoside backbone and the substituents/configurations in the biaryl phosphite/phosphoroamidite moieties to be easily and systematically varied. By carefully selecting the ligand components, therefore, high regio‐ and enantioselectivities (ees up to 98%) and good activities have been achieved in a broad range of mono‐ and disubstituted hindered and unhindered linear and cyclic substrates. The NMR studies on the palladium‐π‐allyl intermediates provide a deeper understanding about the effect of the ligand parameters on the origin of enantioselectivity. They also indicate that the nucleophilic attack takes place predominantly at the allylic terminal carbon atom located trans to the phosphoroamidite moiety.     

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.     

Practical by Ligand Design: A New Class of Monodentate Phosphoramidite Ligands for Rhodium‐Catalyzed Enantioselective Hydrogenations

A new class of low‐cost and easy‐to‐prepare monodentate phosphoramidite ligands (CydamPhos) has been developed from readily accessible and cheap trans‐1,2‐diaminocyclohexane as starting material through a three‐step transformation. This type of ligands exhibited excellent enantioseletivities and high activities in rhodium(I)‐catalyzed asymmetric hydrogenations of dehydro‐α‐amino acid methyl esters 9 (ee: 96.2–99.8 %) and acetylenamides 11 (91.8–98.8 %). The remarkable substituent effects exhibited by the ligands on the enantioselective control of the catalysis are rationalized on the basis of molecular structure of the catalyst precursor.     

Proline‐Derived Aminotriazole Ligands: Preparation and Use in the Ruthenium‐Catalyzed Asymmetric Transfer Hydrogenation

The preparation of 2‐triazolyl‐ and 2‐triazolylmethylpyrrolidines from L ‐proline and L ‐trans‐4‐hydroxyproline is described, along with their evaluation as chiral ligands in ruthenium‐catalyzed asymmetric transfer hydrogenation. Modular evolution of the ligands by introduction of remote substituents is also presented, showing a surprisingly important effect on the performance of the ligands.     

Modification of Chiral Monodentate Phosphine Ligands (MOP) for Palladium‐Catalyzed Asymmetric Hydrosilylation of Cyclic 1,3‐Dienes

Several MOP ligands 5 containing aryl groups at 2′ position of (R)‐2‐(diphenylphosphino)‐1,1′‐binaphthyl skeleton were prepared and used for palladium‐catalyzed asymmetric hydrosilylation of cyclic 1,3‐dienes 6 with trichlorosilane. Highest enantioselectivity was observed in the reaction of 1,3‐cyclopentadiene ( 6a ) catalyzed by a palladium complex (0.25 mol %) coordinated with (R)‐2‐(diphenylphosphino)‐2′‐(3,5‐dimethyl‐4‐methoxyphenyl)‐1,1′‐binaphthyl ( 5f ), which gave (S)‐3‐(trichlorosilyl)cyclopentene of 90% ee.     

Identification of Suitable Ligands for a Transition Metal‐Catalyzed Reaction: Screening of a Modular Ligand Library in the Enantioselective Hydroboration of Styrene

Based on a general modular synthetic scheme, a variety of chiral bidentate P/P‐, P/S‐, P/N‐, and P/Se‐ligands is accessible in an efficient divergent manner starting from phenol or naphthol derived backbone systems. A library of 20 selected ligands was tested in the Rh‐catalyzed asymmetric hydroboration of styrene to give 1‐phenylethanol in up to 91% ee after oxidative work‐up. It was demonstrated that small variations of the ligand structures lead to pronounced, unpredictable differences in the performance of the in situ generated rhodium complexes. The modular approach should be applicable for the identification and optimization of suitable ligands for other transition metal‐catalyzed transformations with comparably low effort.     

tert‐Butanesulfinylphosphines: Simple Chiral Ligands in Rhodium‐Catalyzed Asymmetric Addition of Arylboronic Acids to Electron‐Deficient Olefins

An efficient rhodium complex catalyst system was developed by using a class of simple tert‐butanesulfinylphosphines as bidentate ligands, which solely bear sulfur chirality and combine the advantages of both sulfoxide and phosphine ligands. Excellent activities (in 0.5 hour, up to 99% yield) and enantioselectivities (up to 98% ee) were displayed in Rh‐catalyzed asymmetric 1,4‐additions under mild conditions.     

Modular Phosphine‐Aminophosphine Ligands Based on Chiral 1,2,3,4‐Tetrahydro‐1‐naphthylamine Backbone: A New Class of Practical Ligands for Enantioselective Hydrogenations

A series of new chiral phosphine‐aminophosphine ligands [(R)‐HW‐Phos] has been prepared from (R)‐1,2,3,4‐tetrahydro‐1‐naphthylamine through a two‐step procedure, and successfully applied in the rhodium‐catalyzed asymmetric hydrogenation of various functionalized olefins such as α‐enol ester phosphonates, α‐enamido phosphonates, (Z)‐β‐(acylamino)acrylates and so on. Excellent enantioselectivities have been achieved in the hydrogenation of most substrates tested, demonstrating the high potential of these newly developed phosphine‐aminophosphine ligands in asymmetric catalysis. The present research also discloses that these newly developed phosphine‐aminophosphine ligands are more efficient than that derived from (S)‐1‐phenylethylamine, suggesting that the increased rigidity conferred by a cyclohexyl fragment in these phosphine‐aminophosphine ligands has a positive effect in the asymmetric induction.     

Synthesis of Versatile Building Blocks through Asymmetric Hydrogenation of Functionalized Itaconic Acid Mono‐Esters

The rhodium‐catalyzed asymmetric hydrogenation of several β‐substituted itaconic acid monoesters, using a library of monodentate phosphoramidite and phosphite ligands is described. Two β‐alkyl‐substituted substrates were readily hydrogenated by the rhodium complex Rh(COD)₂BF₄ in combination with (S)‐PipPhos as a ligand resulting in ees of 99 %. In contrast, the corresponding more hindered β‐aryl‐substituted substrates did not exhibit acceptable enantioselectivities under these conditions. However, the use of a 48‐membered ligand library led to the identification of several suitable ligands for these substrates, resulting in ees of 89–99 %. The resulting optically active succinic acid derivatives are potentially useful building blocks for more elaborate compounds, because of the ability to differentiate between the carboxylic acid and the ester groups on either side of the molecule.     

A New Chiral P,N‐Ligand Derived from 1‐Phenylphospholane‐2‐carboxylic Acid (Phenyl‐P‐proline) for Palladium‐Catalyzed Asymmetric Allylic Substitution Reactions

New types of P,N‐ligands, cis‐ and trans‐ 3 , containing a tetrahydroisoquinoline skeleton as an N‐donor were synthesized from (1R,2S)‐1‐phenylphospholane‐2‐carboxylic acid (phenyl‐P‐proline, 1 ). The cis isomer, cis‐ 3 , was found to act as an excellent ligand in palladium‐catalyzed asymmetric allylic substitution reactions. The reactions of 1,3‐diphenyl‐2‐propenyl acetate ( 5 ) with several nucleophiles in the presence of [Pd(π‐allyl)Cl]₂, cis‐ 3 (Pd : ligand=1 : 2), and a base afforded the desired products in high yields with high enantioselectivity. It was suggested that these ligands did not serve as P,N‐bidentate ligands but as P‐monodentate ligands in these reactions.     

Synthesis of Olefin‐Oxazoline Ligands (OlefOx) by Rhodium(III)‐Catalyzed Oxidative Olefination

The rhodium(III)‐catalyzed oxidative olefination of 2‐aryloxazolines is described and has been employed for the synthesis of olefin‐oxazoline ligands (OlefOx). The highly modular synthesis starting from readily available 2‐aryloxazolines can be performed under an atmosphere of air as the terminal oxidant with catalytic amounts of copper(II)‐acetate.     

Highly Selective Copper‐Catalyzed Monoarylation of Aniline

A series of mono‐, bi‐ and tridendate ligands was investigated in the copper‐catalyzed monoarylation of aniline with p‐chloronitrobenzene. Excellent selectivities at high conversions were observed when bridged bisimidazolidenes as well as biphenyl‐bisalkylphosphines were employed. The X‐ray crystal structure of bis(tert‐butyl)biphenylphosphine‐copper complex indicates a significant binding of the metal center to the aryl moiety and, thus, an almost bidendate coordination mode. Chelating bisphosphines, glycol, phenanthroline or other mono‐ to tridendate ligands led to less selective or productive catalysts.     

An Expeditious Copper‐Catalyzed Access to 3‐Aminoquinolinones, 3‐Aminocoumarins and Anilines using Sodium Azide

An efficient copper‐catalyzed in situ C(sp²) NH₂ bond formation to provide a range of 3‐aminoquinolin‐2(1H)‐ones and 3‐aminocoumarins from 3‐bromoquinolinones and 3‐bromocoumarins, respectively, has been achieved. The reaction conditions involve the use of copper powder as the catalyst, eco‐friendly ethanol as the solvent in the presence of pipecolinic acid as the ligand and ascorbic acid as the additive. The efficiency of this practical method was demonstrated in the synthesis of various anilines.     

Switchable Stereoselectivity: The Effects of Substituents on the D2‐Symmetric Biphenyl Backbone of Phosphoramidites in Copper‐Catalyzed Asymmetric Conjugate Addition Reactions with Triethylaluminium

A highly enantioselective copper‐catalyzed conjugate addition with triethylaluminium was developed using phosphoramidite ligands bearing a D₂‐symmetric biphenyl backbone. For these ligands we demonstrated that the 3,3′,5,5′‐substituents on the biphenyl backbone can completely reverse the absolute configuration of the products.