Ruthenium‐Catalyzed Tandem‐Isomerization/Asymmetric Transfer Hydrogenation of Allylic Alcohols

A one‐pot procedure for the direct conversion of racemic allylic alcohols to enantiomerically enriched saturated alcohols is presented. The tandem‐isomerization/asymmetric transfer hydrogenation process is efficiently catalyzed by [{Ru(p‐cymene)Cl₂}₂] in combination with the α‐amino acid hydroxyamide ligand 1 , and performed under mild conditions in a mixture of ethanol and THF. The saturated alcohol products are isolated in good to excellent chemical yields and in enantiomeric excess up to 93 %.     

Catalytic Asymmetric Transfer Hydrogenation of Imines: Recent Advances

In this review article recent developments in the asymmetric transfer hydrogenation of imines from 2008 up to today are presented. The main methodology involves either metal‐catalyzed procedures in the presence of a chiral ligand or organocatalyzed technologies using a Hantzsch ester and a chiral BINOL‐derived phosphoric acid. The most important procedures are collected, paying special attention to the application of this methodology in synthetic organic chemistry.

     

Nickel‐Catalyzed Asymmetric Transfer Hydrogenation of Hydrazones and Other Ketimines

We report the use of nickel catalysts for the catalytic transfer hydrogenation of hydrazones and other ketimines with formic acid. Strongly donating bisphosphines must be used to support the catalysts. As in enzymatic catalysis, attractive weak interactions may be important for stereochemical control by the nickel/binapine catalyst.     

Chiral DMAP‐N‐oxides as Acyl Transfer Catalysts: Design,Synthesis, and Application in Asymmetric Steglich Rearrangement

A DMAP‐N‐oxide, featuring an α‐amino acid as the chiral source, was developed, synthesized and applied in asymmetric Steglich rearrangement. A series of O‐acylated azlactones afforded C‐acylated azlactones possessing a quaternary stereocenter in high yields (up to 97 % yield) and excellent enantioselectivities (up to 97 % ee). Compared to the widespread use of pyridine nitrogen, which serves as the nucleophilic site in the asymmetric acyl transfer reaction, we discovered that chiral DMAP‐N‐oxides, in which the oxygen now acts as the nucleophilic site, are efficient acyl transfer catalysts. Our finding might open a new door for the development of chiral DMAP‐N‐oxides for asymmetric acyl transfer reactions.     

Phenylene‐Coated Magnetic Nanoparticles that Boost Aqueous Asymmetric Transfer Hydrogenation Reactions

Phenylene‐coated organorhodium‐functionalized magnetic nanoparticles are developed through co‐condensation of chiral 4‐(trimethoxysilyl)ethyl)phenylsulfonyl‐1,2‐diphenylethylene‐diamine and 1,4‐bis(triethyoxysilyl)benzene onto Fe₃O₄ followed complexation with [{Cp*RhCl₂}₂]. This magnetic catalyst exhibits excellent catalytic activity and high enantioselectivity in asymmetric transfer hydrogenation in aqueous medium. Such activity is attributed to the high hydrophobicity and the confined nature of the chiral organorhodium catalyst. The magnetic catalyst can be easily recovered by using a small external magnet and it can be reused for at least 10 times without loss of its catalytic activity. This characteristic makes it an attractive catalyst for environmentally friendly organic syntheses.     

Design of a Genetic Algorithm for the Simulated Evolution of a Library of Asymmetric Transfer Hydrogenation Catalysts

Breeding new catalysts : A library of 1980 catalysts was designed for asymmetric hydrogen transfer to acetophenone. The library was submitted to evaluation and further simulated evolution experiments, based on a genetic algorithm (see scheme). We demonstrated that it was easily possible to get 5–6 of the ten best catalysts, while investigating only 10% of the library.

     

Asymmetric Reduction of 2‐Chloro‐3‐oxo Esters by Transfer Hydrogenation

Asymmetric reduction of 2‐chloro‐3‐oxo esters was achieved by catalytic transfer hydrogenation using [RuCl₂(p‐cymene)](S,S)‐TsDPEN as the chiral catalyst and HCOOH‐Et₃N as the hydrogen source. Moderate to good yields (up to 85%) and good enantioselectivities (up to 98% ee) were obtained.     

Asymmetric Transfer Hydrogenation of gem-Difluorocyclopropenyl Esters: Access to Enantioenriched gem-Difluorocyclopropanes

Catalytic enantioselective access to disubstituted functionalized gem-difluorocyclopropanes, which are emerging fluorinated motifs of interest in medicinal chemistry, was achieved through asymmetric transfer hydrogenation of gem-difluorocyclopropenyl esters, catalyzed by a Noyori–Ikariya (p-cymene)-ruthenium(II) complex, with (N-tosyl-1,2-diphenylethylenediamine) as the chiral ligand and isopropanol as the hydrogen donor. The resulting cis-gem-difluorocyclopropyl esters were obtained with moderate to high enantioselectivity (ee=66–99 %), and post-functionalization reactions enable access to valuable building blocks incorporating a cis- or trans-gem-difluorocyclopropyl motif.     

Enantioselective Synthesis of Alcohols and Amines by Iridium‐Catalyzed Hydrogenation,Transfer Hydrogenation,and Related Processes

The preparation of chiral alcohols and amines by using iridium catalysis is reviewed. The methods presented include the reduction of ketones or imines by using hydrogen (hydrogenations), isopropanol, formic acid, or formate (transfer hydrogenations). Also dynamic and oxidative kinetic resolutions leading to chiral alcohols and amines are included. Selected literature reports from early contributions to December 2012 are discussed.     

Development of a Continuous‐Flow System for Asymmetric Hydrogenation Using Self‐Supported Chiral Catalysts

Well‐designed, self‐assembled, metal–organic frameworks were constructed by simple mixing of multitopic MonoPhos‐based ligands ( 3 ; MonoPhos=chiral, monodentate phosphoramidites based on the 1,1′‐bi‐2‐naphthol platform) and [Rh(cod)₂]BF₄ (cod=cycloocta‐1,5‐diene). This self‐supporting strategy allowed for simple and efficient catalyst immobilization without the use of extra added support, giving well‐characterized, insoluble (in toluene) polymeric materials ( 4 ). The resulting self‐supported catalysts ( 4 ) showed outstanding catalytic performance for the asymmetric hydrogenation of a number of α‐dehydroamino acids ( 5 ) and 2‐aryl enamides ( 7 ) with enantiomeric excess (ee) ranges of 94–98 % and 90–98 %, respectively. The linker moiety in 4 influenced the reactivity significantly, albeit with slight impact on the enantioselectivity. Acquisition of reaction profiles under steady‐state conditions showed 4 h and 4 i to have the highest reactivity (turnover frequency (TOF)=95 and 97 h^?1 at 2 atm, respectively), whereas appropriate substrate/catalyst matching was needed for optimum chiral induction. The former was recycled 10 times without loss in ee (95–96 %), although a drop in TOF of approximately 20 % per cycle was observed. The estimation of effective catalytic sites in self‐supported catalyst 4 e was also carried out by isolation and hydrogenation of catalyst–substrate complex, showing about 37 % of the Rh^I centers in the self‐supported catalyst 4 e are accessible to substrate 5 c in the catalysis. A continuous flow reaction system using an activated C/ 4 h mixture as stationary‐phase catalyst for the asymmetric hydrogenation of 5 b was developed and run continuously for a total of 144 h with >99 % conversion and 96–97 % enantioselectivity. The total Rh leaching in the product solution is 1.7 % of that in original catalyst 4 h .     

Recent Developments in Asymmetric Phase‐Transfer Reactions

Phase‐transfer catalysis has been recognized as a powerful method for establishing practical protocols for organic synthesis, because it offers several advantages, such as operational simplicity, mild reaction conditions, suitability for large‐scale synthesis, and the environmentally benign nature of the reaction system. Since the pioneering studies on highly enantioselective alkylations promoted by chiral phase‐transfer catalysts, this research field has served as an attractive area for the pursuit of “green” sustainable chemistry. A wide variety of asymmetric transformations catalyzed by chiral onium salts and crown ethers have been developed for the synthesis of valuable organic compounds in the past several decades, especially in recent years.     

Comparative Study of Bifunctional Mononuclear and Dinuclear Amidoiridium Complexes with Chiral C−N Chelating Ligands for the Asymmetric Transfer Hydrogenation of Ketones

A series of new bifunctional C?N chelating Ir complexes possessing a metal/NH group was synthesized by cyclometalation of optically active primary benzylic amines such as O‐silylated (S)‐2‐amino‐2‐phenylethanols ( 1 a and 1 a’ ), (R)‐5‐amino‐6,7,8,9‐tetrahydro‐5H‐benzocycloheptene ( 1 b ), and (R)‐1‐phenyl‐2,2‐dimethylpropylamine ( 1 c ). Although treatment of KOtBu with the amine complexes originating from 1 a and 1 a’ afforded amido‐bridged dinuclear complexes ( 3 a and 3 a’ ), more sterically hindered complexes were solely transformed into the coordinatively unsaturated mononuclear amido complexes ( 3 b and 3 c ), which can serve as real catalyst species in the asymmetric transfer hydrogenation. The structural difference in the C?N chelate framework markedly affected the catalytic performance. Among them, amido complex 3 c showed a pronounced ability to catalyze the transfer hydrogenation of acetophenone in 2‐propanol, even at a low temperature of ?30 °C. A hydridoiridium complex ( 4 c ) was also identified in the reaction of 3 c in 2‐propanol, which provides mechanistic insights into the enantiodiscriminating step in the hydrogen transfer to prochiral ketones.     

手性羰基铁体系催化酮的不对称氢转移氢化

手性羰基铁络合物很少被用于芳香酮的不对称氢转移氢化.利用不同的羰基铁络合物与手性双胺双膦配体现场络合,形成手性胺膦铁催化体系.考察了它们对多种芳香酮的不对称氢转移催化氢化性能.结果表明,三核的手性胺膦铁簇合物是催化芳香酮不对称氢转移氢化的较好体系.当用三核的铁簇合物[Et₃NH]⁺[HFe₃(CO)₁₁]^-体系催化1,1-二苯基丙酮的氢化时,最高可获得98%的对映选择性.通过现场红外光谱测定,揣测羰基铁簇合物Fe₃(CO)₁₂在催化反应过程中保持三核的簇合物的簇骼不变.     

Asymmetric Transfer and Pressure Hydrogenation with Earth‐Abundant Transition Metal Catalysts

The asymmetric transfer and pressure hydrogenation of various unsaturated substrates provides a succinct pathway to important chiral intermediates and products such as chiral alcohols, amines, and alkanes. The use of earth‐abundant transition metals such as Fe, Co, Ni, and Cu in hydrogenation reactions provides an attractive alternative to traditionally used metals such as Ru, Rh, Ir, and Pd because they are comparatively inexpensive, less toxic, and as their name suggests, more abundant in nature. Earth‐abundant transition metal‐catalyzed asymmetric hydrogenation is rapidly becoming an important area of research. This review summarizes advances in the asymmetric hydrogenation of unsaturated bonds (ketones, imines, and alkenes) with earth‐abundant transition metals.     

Mechanistic Investigations into the Asymmetric Transfer Hydrogenation of Ketones Catalyzed by Pseudo‐Dipeptide Ruthenium Complexes

Lithium‐powered : A kinetic investigation into the asymmetric transfer hydrogenation of non‐activated aryl alkyl ketones, catalyzed by N‐Boc‐protected α‐amino acid hydroxyamide ruthenium–arene complexes, has revealed that the reactions proceed through an unprecedented bimetallic outer‐sphere mechanism. Under optimized conditions, these catalysts provide access to secondary alcohols in high yields and with excellent enantioselectivities (>99 % ee).