Monitoring Surface Processes During Heterogeneous Asymmetric Hydrogenation of Ketones on a Chirally Modified Platinum Catalyst by Operando Spectroscopy

Surface processes occurring at the catalytic chiral surface of a cinchona‐modified Pt catalyst during the asymmetric hydrogenation of activated ketones have been monitored for the first time using operando ATR‐IR spectroscopy. Fundamental information about this catalytic system could be gained, including the chiral modification process of the catalyst, the surface interaction of reactant ketone with preadsorbed chiral modifier, the role of hydrogen as well as the influence of the product enantiomers in the catalytic cycle. The formation of a diastereomeric transient surface complex between ketone and chiral modifier was found to be related to the ketone consumption. Among the studied activated ketones, a correlation between stereoselection and the strength of the intermolecular hydrogen bond was identified. Dissociated hydrogen from the catalytic surface is found to play a crucial role in the formation of the diastereomeric surface complex.     

联萘衍生物作为手性配体在不对称氢化中的应用

综述了近年来联萘衍生物作为手性配体构成的金属络合物在前手性烯、酮及亚胺的不对称氢化反应中的应用。     

Asymmetric Hydrogenation of Pyridinium Salts with an Iridium Phosphole Catalyst

Iridium‐catalyzed asymmetric hydrogenation of N‐alkyl‐2‐alkylpyridinium salts provided 2‐aryl‐substituted piperidines with high levels of enantioselectivity. Simple benzyl and other alkyl groups successfully activated the challenging pyridine substrates toward hydrogenation. The use of the unusual chiral‐phosphole‐based MP²‐SEGPHOS was the key to the success of this approach which provides a versatile and practical procedure for the synthesis of chiral piperidines.     

Chiral Modification of Platinum by Co‐Adsorbed Cinchonidine and Trifluoroacetic Acid: Origin of Enhanced Stereocontrol in the Hydrogenation of Trifluoroacetophenone

Cinchonidine (CD) adsorbed onto a platinum metal catalyst leads to rate acceleration and induces strong stereocontrol in the asymmetric hydrogenation of trifluoroacetophenone. Addition of catalytic amounts of trifluoroacetic acid (TFA) significantly enhances the enantiomeric excess from 50 to 92 %. The origin of the enantioselectivity bestowed by co‐adsorbed CD and TFA is investigated by using in situ attenuated total reflection infrared spectroscopy and modulation excitation spectroscopy. Molecular interactions between the chiral modifier (CD), acid additive (TFA) and the trifluoro‐activated substrate at the solid–liquid interface are elucidated under conditions relevant to catalytic hydrogenations, that is, on a technical Pt/Al₂O₃ catalyst in the presence of H₂ and solvent. Monitoring of the unmodified and modified surface during the hydrogenation provides an insight into the phenomenon of rate enhancement and the crucial interactions of CD with the ketone, corresponding product alcohol, and TFA. Comparison of the diastereomeric interactions occurring on the modified surface and in the liquid solution shows a striking difference for the chiral preferences of CD. The spectroscopic data, in combination with calculations of molecular structures and energies, sheds light on the reaction mechanism of the heterogeneous asymmetric hydrogenation of trifluoromethyl ketones and the involvement of TFA in the diastereomeric intermediate surface complex: the quinuclidine N atom of the adsorbed CD forms an N?H?O‐type hydrogen‐bonding interaction not only with the trifluoro‐activated ketone but also with the corresponding alcohol and the acid additive. Strong evidence is provided that it is a monodentate acid/base adduct in which the carboxylate of TFA resides at the quinuclidine N‐atom of CD, which imparts a better stereochemical control.     

Trinuclear Rhodium Complexes and Their Relevance for Asymmetric Hydrogenation

Various trinuclear rhodium complexes of the type [Rh₃(PP)₃(μ₃‐OH)_x(μ₃‐OMe)_2?x]BF₄ (where PP=Me‐DuPhos, dipamp, dppp, dppe; different ligands and μ‐bridging anions) are presented, which are formed upon addition of bases such as NEt₃ to solvate complexes [Rh(PP)(solvent)₂]BF₄. They were extensively characterized by X‐ray diffraction and NMR spectroscopy (¹⁰³Rh, ³¹P, ¹³C, ¹H). Their in situ formation resulting from basic additives (NEt₃) or basic prochiral olefins (without addition of another base) can cause deactivation of the asymmetric hydrogenation. This effect can be reversed by means of acidic additives.     

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 .     

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.     

Broader,Greener, and More Efficient: Recent Advances in Asymmetric Transfer Hydrogenation

Asymmetric transfer hydrogenation has become a practically useful tool in reduction chemistry in the last decade or so. This was largely triggered by the seminal work of Noyori and co‐workers in the mid‐1990s and is driven by its complementing chemistry to hydrogenation employing H₂. This Focus Review attempts to present a “holistic” overview on the advances in the area, focusing on the achievements recorded around the last three years. These include more‐efficient and “greener” metal catalysts, catalysts that enable hydrogenation as well as transfer hydrogenation, biomimetic and organocatalysts, and their applications in the reduction of C?O, C?N, and C?C bonds. Also highlighted are efforts in the development of environmentally benign and reusable catalytic systems.     

Mechanistic Insights into Cu-Catalyzed Asymmetric Aldol Reactions: Chemical and Spectroscopic Evidence for a Metalloenolate Intermediate

In situ IR spectroscopy and transmetalation experiments confirm a postulated catalytic cycle. The metalloenolate 1 describes the active intermediate in the aldol reaction catalyzed by [CuF₂{(S)-tol-binap}] (see reaction scheme). (S)-tol-binap=(S)-(−)-2,2′-bis(di-p-tolylphosphanyl)-1,1′-binaphthyl.     

Scorpio-Ligand: Synthesis of Biphenyl-Dihydroazepine Phosphoramidite Ligands for Asymmetric Hydrogenation

A novel dihydroazepine-bridged BIPHEP phosphoramidite ligand with an amino acid moiety in the backbone was synthesized and evaluated in the Rh-catalyzed asymmetric hydrogenation. The scorpion tail-like amino acid backbone is capable of hydrogen bond formation and able to shift the rotamer composition of the biphenyl axis with the two scissor-like arms. Pivaloyl-l -valine was studied as chiral selector unit and compared with pivaloylglycine as the achiral reference substance. The enantiomerization barrier of the pivaloylglycine-modified biphenylamide was determined to be ΔG^≠=110 kJ/mol. In the case of pivaloyl-l -valine, the (S_ax) isomer is thermodynamically favored. Due to the relatively high barrier, the ligand is atropisomeric at room temperature and allows the preparative separation of the stereoisomers. The obtained phosphoramidite ligands were separated by chiral HPLC. For the first eluting rotamer, Rh complex ([Rh(cod)(L)₂]BF₄) was generated in situ and examined in the enantioselective hydrogenation of 2-acetamidoacrylate and methyl 2-acetamido-3-phenylacrylate, achieving enantiomeric excesses of up to 94 %.     

Synthesis of Dendritic BINAP Ligands and Their Applications in Asymmetric Hydrogenation

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金属/金属氧化物纳米粒子在不对称氢化和氢转移反应中的应用研究进展

近年来,金属/金属氧化物纳米粒子催化的不对称氢化和氢转移反应已经成为催化领域的前沿和研究热点之一. 金属/金属氧化物纳米粒子的催化模式类似于“纳米反应器”,底物可以通过有机包覆层扩散至催化中心,局部的高催化剂浓度通常可以极大地提高催化反应转换数（TON）和转化频率（TOF）. 在以纳米金属为催化活性中心方面,Orito纳米铂体系获得最多的关注,科学家们从手性修饰剂的结构改造、催化剂载体的选择、不同的反应介质、纳米催化剂的形貌和催化反应机理等方面开展了较为系统的研究,并取得重要进展. 此外,纳米钯、铑、钌、铱和铁等金属纳米催化剂也在烯烃、酮和亚胺等化合物的不对称氢化和氢转移反应中表现出良好的催化性能,特别是纳米铱和铁催化剂已获得95%以上的对映选择性. 在金属/金氧化物纳米粒子为催化剂载体方面,其催化不对称氢化及氢转移反应的效率及对映选择性可与均相催化剂相媲美,同时还解决了均相催化剂难于回收再循环的缺陷. 本文简要介绍了近年来手性金属纳米催化剂在不对称氢化和氢转移反应领域的研究进展,讨论了相关反应的催化机理,并对该领域仍存在的问题和未来的发展方向进行了展望.     

Recyclable Mn(I) Catalysts for Base-Free Asymmetric Hydrogenation: Mechanistic,DFT and Catalytic Studies

We report here a mechanistic, DFT and catalytic study on a series of Mn(I) complexes 1 , 2 ( a – d ), 3 , 4 . The studies apprehended the requirements for Mn(I) complexes to be active in both asymmetric direct ( AH ) and transfer hydrogenations ( ATH ). The investigations disclosed 6 vital factors accelerating the formation of a resting species, which plays a significant role in lowering the activities of the Mn(I) complex 1 in ATH and AH , respectively. In addition, we also report here a base free Mn(I) catalyzed ATH of aryl alkyl ketones with high enantioselectivity (up to 98 % ee) and improved activity. More significantly, a novel and simple single-step process for recycling the resting species from the catalytic leftover has been discovered. Notably, the studies provide evidence for the existence of two different temperature dependent mechanisms for AH and ATH , in contrast to previous studies on related systems.     

Asymmetric Hydrogenation with Highly Active IndolPhos–Rh Catalysts: Kinetics and Reaction Mechanism

The mechanism of the IndolPhos–Rh‐catalyzed asymmetric hydrogenation of prochiral olefins has been investigated by means of X‐ray crystal structure determination, kinetic measurements, high‐pressure NMR spectroscopy, and DFT calculations. The mechanistic study indicates that the reaction follows an unsaturate/dihydride mechanism according to Michaelis–Menten kinetics. A large value of K_M (K_M=5.01±0.16 M ) is obtained, which indicates that the Rh–solvate complex is the catalyst resting state, which has been observed by high‐pressure NMR spectroscopy. DFT calculations on the substrate–catalyst complexes, which are undetectable by experimental means, suggest that the major substrate–catalyst complex leads to the product. Such a mechanism is in accordance with previous studies on the mechanism of asymmetric hydrogenation reactions with C₁‐symmetric heteroditopic and monodentate ligands.