Theoretical investigation on the mechanisms of transfer hydrogenation of ketones catalyzed by iridium complexes

The detailed catalytic mechanisms on transfer hydrogenation of ketones are explored by employing the representative reaction of 3-pentanone and 2-propanol catalyzed by the model complex IrH₃[(Me₂PC₂H₄)₂NH], derived from the catalyst IrH₃[(ⁱPr₂PC₂H₄)₂NH], with the aid of the density functional theory calculations. The geometrical transformation from an octahedron to a Y-type involved in the catalytic cycle is also elucidated in terms of molecular theory of transition metal complexes. The trend for the variation of Ir-N bond distance is also analyzed.     

N-Alkylation of carbamates and amides with alcohols catalyzed by a CpIr complex

New atom-economical catalytic systems consisting of [Cp^∗IrCl₂]₂/NaOAc (Cp^∗=pentamethylcyclopentadienyl) for the N-alkylation of carbamates and amides using alcohols as alkylating agents under solvent-free conditions have been developed. For example, the reaction of n-butyl carbamate with benzyl alcohol in the presence of [Cp^∗IrCl₂]₂ (5.0 mol % Ir) and NaOAc (5.0 mol %) at 130 °C under the absence of solvent gives n-butyl N-benzylcarbamate in the yield of 94%. The present catalytic system is applicable to not only carbamates but also amides, and only harmless water is produced as co-product.     

含有手性BINAP基团的共轭微孔聚合材料应用于喹啉高效不对称氢化反应

喹啉不对称氢化反应是不对称氢化研究的重点之一。其氢化产物四氢喹啉不仅是重要的有机合成中间体,同时也是自然界中生物碱的结构单元和生物活性化合物。周永贵研究组首次报道了手性(R)-MeO-Biphep/Ir体系成功用于喹啉的不对称催化,取得了非常好的反应结果。随后他们对喹啉底物进行了拓展,包括拥有特殊取代基的喹啉衍生物,均取得了良好的反应结果。后来多个研究组对该反应进行了深入研究并开发出了多个不同手性膦配体的Ir催化体系。虽然喹啉不对称氢化反应取得了很大的发展,但是该均相反应体系只能在高的反应催化剂用量下才能实现好的结果。进一步研究发现手性配体与金属Ir络合后形成反应活性物种,但后者可发生二聚或三聚,生成的产物是不具有催化活性的,从而导致了反应体系需要高的催化剂的用量。为此人们做了大量研究。范青华研究组通过对BINAP基团上嫁接大空间位阻的枝状分子合成了一系列新的手性BINAP配体,在与Ir络合后,表现出远高于均相催化剂的反应活性,且可循环利用。在该体系中,大位阻的枝状分子起到了阻隔活性物种二聚、三聚的作用,因而提高了反应活性。后来周永贵研究组也尝试通过改变有机配体的方法来实现高的反应活性。他们选择改变手性双膦配体上P原子所连接有机配体的空间位阻来实现对活性物种多聚的控制。实验同样取得了很好的反应效果。对于均相反应体系,我们只能通过这种改变有机配体空间位阻的方式来降低活性物种多聚的可能性,那么如何彻底阻止这种多聚呢？非均相体系给我们提供了很好的研究思路,但如何将非均相体系引入到喹啉不对称氢化反应体系当中成为了难点。
　　共轭微孔聚合物(CMPs)的发展使得手性催化体系很容易从均相转变到非均相。这种材料具有较高的比表面积和固定的开放孔道结构,可应用于非均相催化中。且制备相对容易。我们可以将手性双膦配体作为材料制备配体嫁接到CMPs材料当中。在这种材料当中,手性配体会以有序、空间分离的方式分布,在与Ir配合后应用于喹啉不对称氢化反应中,从而从根本上避免了活性物种多聚的可能因此反应活性提高。我们曾首次成功合成了一系列含有手性(R)-Binap基团的共轭微孔聚合材料-BINAP-CMPs,并将其用于β-酮酸酯的不对称氢化反应当中,取得了很好的催化效果。手性BINAP基团均匀、有序地分散于该材料中。我们尝试利用BINAP-CMPs固有的空间隔离效应,将其应用于喹啉的不对称氢化反应中,结果表明,在相同条件下,非均相BINAP-CMPs/Ir催化体系的TOF值是340 h–1,是均相BINAP/Ir体系(100 h–1)3倍,反应的对映体选择性与均相相当;另外该催化体系多循环利用次后仍可以保持高的反应活性。我们还发现材料结构性质对反应结果的影响很大,材料的比表面积和孔容更大反应结果更好。     

Asymmetric transfer hydrogenation of aromatic ketones catalyzed by the iridium hydride complex under ambient conditions

The chiral Ir catalytic system generated in situ from iridium hydride complex and chiral diaminodiphosphine ligand was employed in asymmetric transfer hydrogenation of aromatic ketones to give the corresponding optically active alcohols, with up to 99% ee in high yield were obtained even when the substrate-to-catalyst molar ratio reached 10000:1.     

pH-Regulated transfer hydrogenation of quinoxalines with a Cp*Ir-diamine catalyst in aqueous media

The combination of [Cp*IrCl₂]₂ with N-(2-aminoethyl)-4-(trifluoromethyl)benzenesulfonamide constitutes an efficient catalyst for selective transfer hydrogenation of a variety of quinoxalines in water with HCOONa as the hydrogen source, affording the corresponding tetrahydroquinoxalines in good to excellent yields. The catalyst is air-stable, and the reduction could be performed without nitrogen protection. The aqueous phase reduction is shown to be highly pH-dependent, with acidic pH leading to better results. There exits a pH window for optimum rate, and the use of HOAc/NaOAc buffer solution is essential for maintaining a stable pH during the reaction.     

Binuclear ruthenium(II) pyridazine complex catalyzed transfer hydrogenation of ketones

A convenient and general method of synthesis of binuclear ruthenium(II) pyridazine complex was reported. The synthesized complex was characterized by analytical and spectral methods. The structure of the complex was confirmed by X-ray diffraction technique and was found to be an efficient catalyst for the transfer hydrogenation of ketones with excellent conversions in the presence of isopropanol/KOH at 82 °C. The effect of solvents, bases, and different catalyst/substrate ratio for the reaction was also investigated.     

非负载纳米多孔钯催化喹啉及其衍生物的化学选择性氢化反应:H_2分子异裂（英文）

纳米多孔金属是近十年发展起来的一类具有三维通孔结构的新型功能材料,其由纳米尺度的细孔和韧带构成,具有极大的比表面积;它还是一种无毒无载体的宏观材料,并且易制备、易回收和重复利用,因此作为高效的非均相催化剂已逐渐引起人们的重视.1,2,3,4-四氢喹啉是许多医药、农药、染料和天然产物的重要骨架.通过喹啉及其衍生物的选择性加氢反应制备1,2,3,4-四氢喹啉,具有原子利用率高和原料易得等优点.在过去,已经开发了许多类型的均相和非均相催化体系,并成功地用于催化喹啉及其衍生物的选择性加氢反应.尽管非均相催化体系具有诸多优点,但仍存在H_2压力(10–50 atm)和反应温度(60–150℃)相对较高的缺点.因此,开发更加温和条件下的喹啉及其衍生物的选择性加氢反应具有重要意义.此外,在喹啉及其衍生物的加氢反应过程中,H_2分子在非均相催化剂表面的裂解模式,即均裂还是异裂尚不清楚.因此,本文采用新型非均相催化剂纳米多孔钯,研究了喹啉及其衍生物的选择性加氢反应,在相对较低的H_2压力(2–5 atm)和温度(室温–50℃)下实现了目标反应,高收率、高选择性地得到1,2,3,4-四氢喹啉化合物.在最佳反应条件下,对底物的适用范围进行了考察.结果表明,各种含喹啉结构单元的化合物均能顺利发生反应,产物收率在62%–95%.而且该反应对甲基、甲氧基、羟基、酯基、醛基、酰胺基、卤素(F,Cl和Br)等官能团具有较好的兼容性.苯环上取代基的电子效应对反应有一定的影响,吸电子基有利于目标反应的进行.反应完成后,纳米多孔钯催化剂很容易回收,且循环使用多次后,仍未见催化活性降低.扫描电镜和透射电镜结果发现,循环使用后的纳米多孔钯催化剂结构没有发生明显改变,表明其结构稳定.浸出实验结果证明,没有钯原子浸出到反应液中,表明该纳米多孔钯催化反应属于多相催化过程.喹啉的选择性氢化反应被放大到克级的规模时,目标产物的收率仅略有降低,说明该方法具有很好的实用性.通过动力学实验发现,随着反应的进行,反应速率不断加快,表明反应过程中生成的乙胺和1,2,3,4-四氢喹啉同样扮演着路易斯碱性添加剂的角色,促进了反应的进行.通过反应机理研究,揭示了H–H键在纳米多孔钯表面发生了异裂,原位形成的Pd–H物种作为弱亲核试剂,对目标反应的选择性控制起到了至关重要的作用.     

Recent topics of transfer hydrogenation

A number of transition metal catalysts have been developed for transfer hydrogenation of organic molecules. This method provides a useful process for the reduction of unsaturated molecules without the need for explosive hydrogen gas. An important development in this area is the design of new ligands that improve activity and selectivity under mild reaction conditions. Polydentate ligands are good candidates for producing high performance metal catalysts. This digest describes recent developments in transfer hydrogenation as well as asymmetric reactions using metal catalysts containing polydentate ligand systems.     

Quinoline-functionalized N-heterocyclic carbene complexes of iridium: Synthesis, structures and catalytic activities in transfer hydrogenation

Iridium complexes containing quinoline-functionalized N-heterocyclic carbene (NHC) ligands have been synthesized by the transmetalation route from silver carbene precursors. The silver complexes undergo a facile reaction with [Ir(COD)Cl]₂ (COD = 1,5-cyclooctadiene) to yield a series of carbene complexes [(NHC)Ir(COD)Cl] (NHC = 3-methyl-1-(8-quinolylmethyl)imidazole-2-ylidene (2a); 3-n-butyl-1-(8-quinolylmethyl)imidazole-2-ylidene (2b); 3-benzyl-1-(8-quinolylmethyl)imidazole-2-ylidene (2c); 1,3-di(8-quinolylmethyl)imidazole-2-ylidene (2d). The coordinated COD was replaced by carbon monoxide to yield the corresponding carbonyl species [(NHC)Ir(CO)₂Cl] (3). Complexes 2 and 3 have been characterized by IR, ESI-MS, ¹H and ¹³C NMR and elemental analyses. The molecular structures of complexes 2b and 2c have been confirmed by single-crystal X-ray diffraction. Two analogous Ir(I) complexes 5 and 6 with naphthalene-containing NHC have also been synthesized and characterized. These Ir(I) complexes in the current work have been proved to be active catalysts in the transfer hydrogenation of ketones to alcohols using 2-propanol as the hydrogen source.     

Transition metal free transfer hydrogenation of ketones promoted by 1,3-diarylimidazolium salts and KOH

An efficient transition metal free and greener catalytic system was developed for the selective transfer hydrogenation of saturated ketones to alcohols. This was achieved by the use of 1,3-diarylimidazolium salts in the presence of KOH as a promoter for the reaction. When the range of substrates was expanded to include unsaturated ketones, selective reduction of the double bond occurred. The catalyst efficiency was comparable to some established transition metal catalyzed systems. The current system utilizes mild aerobic reaction conditions compared to the inert atmosphere conditions required for the corresponding metal based systems.     

pH-Dependent catalytic activity and chemoselectivity in transfer hydrogenation catalyzed by iridium complex with 4,4'-dihydroxy-2,2'-bipyridine

Transfer hydrogenation catalyzed by an iridium catalyst with 4,4'-dihydroxy-2,2'-bipyridine (DHBP) in an aqueous formate solution exhibits highly pH-dependent catalytic activity and chemoselectivity. The substantial change in the activity is due to the electronic effect based on the acid-base equilibrium of the phenolic hydroxyl group of DHBP. Under basic conditions, high turnover frequency values of the DHBP complex, which can be more than 1000 times the value of the unsubstituted analogue, are obtained (up to 81 000 h(-1) at 80 degrees C). In addition, the DHBP catalyst exhibits pH-dependent chemoselectivity for alpha,beta-unsaturated carbonyl compounds. Selective reduction of the C=C bond of enone with high activity are observed under basic conditions. The ketone moieties can be reduced with satisfactory activity under acidic conditions. In particular, pH-selective chemoselectivity of the C=O versus C=C bond reduction was observed in the transfer hydrogenation of cinnamaldehyde.     

High efficient iron-catalyzed transfer hydrogenation of quinolines with Hantzsch ester as hydrogen source under mild conditions

A highly efficient transfer hydrogenation of quinolines with Hantzsch ester as hydrogen source in the presence of 1 mol% Fe(OTf)₂ under mild conditions has been developed. A series of substituted 1,2,3,4-tetrahydroquinoline derivatives were afforded in excellent yields with good functional group tolerance.     

Magnetically recoverable supported ruthenium catalyst for hydrogenation of alkynes and transfer hydrogenation of carbonyl compounds

A ruthenium (Ru) catalyst supported on magnetic nanoparticles (NiFe₂O₄) has been successfully synthesized and used for hydrogenation of alkynes at room temperature as well as transfer hydrogenation of a number of carbonyl compounds under microwave irradiation conditions. The catalyst shows excellent selectivity toward the desired products with very high yield even after five repeated uses.     

Upgrading and expanding the scope of homogeneous transfer hydrogenation

Transfer hydrogenation using inexpensive and safe hydrogen sources of alcohols and formic acid has been studied thoroughly over the decades. In particular, the asymmetric version offers the state-of-the-art methods to obtain optically active alcohols and amines, which are valuable synthetic intermediates in the field of pharmaceutical and agrochemical industry. This digest paper highlights the recent notable advances in homogeneous transfer hydrogenation using transition metal complexes, especially in direction to establish practical greener processes by upgrading the catalyst performance or by expanding the scope of reducible functional groups.     

Synthesis of quinolines from amino alcohol and ketones catalyzed by [IrCl(cod)]2 or IrCl3 under solvent-free conditions

2-Aminobenzyl alcohol reacted with 2 equiv amount of ketones under the influence of [IrCl(cod)]₂ or IrCl₃ and KOH without any solvent, giving the corresponding quinoline derivatives in good yields.     

A practical and highly efficient transfer hydrogenation of aryl azides using a [Ru(p-cymene)Cl2]2 catalyst and sodium borohydride

Various aniline derivatives were synthesized by selective reduction of aryl azides in the presence of a dichloro(p-cymene)ruthenium(II) dimer ([Ru(p-cymene)Cl₂]₂) via hydrolysis of sodium borohydride. The hydrogenation reactions were carried out in aqueous media at room temperature. Most of the reactions were completed within 10 min with quantitative yields.     

Asymmetric transfer hydrogenation of ketones catalyzed by nickel complex with new PNO-type ligands

The new polydentate mixed-N,P,O chiral ligands have been synthesized by the condensation of bis（o-formylphenyl）- phenylphosphane and R-phenylglycinol in CHCl₃,and fully characterized by IR,NMR and EIMS spectra.These ligands were employed with a simple Ni complex Ni（PPh_s）₂Cl₂ in situ as catalytic systems for asymmetric transfer hydrogenation of ketones,and the corresponding optical alcohols were obtained with up to 84%ee under mild conditions.     

Oxidation of primary and secondary alcohols catalyzed by a pentamethylcyclopentadienyliridium complex

The oxidation of primary and secondary alcohols is carried out in acetone under mild conditions using catalytic amounts of [Cp*IrCl₂]₂ and K₂CO₃. Primary alcohols are converted into the corresponding aldehydes with high selectivity in good yields. Secondary alcohols are readily oxidized to ketones with smaller amounts of the catalyst.     

Synthesis of new chiral 2-functionalized-1,2,3,4-tetrahydroquinoline derivatives via asymmetric hydrogenation of substituted quinolines

The asymmetric hydrogenation of a series of quinolines substituted by a variety of functionalized groups linked to the C2 carbon atom is providing access to optically enriched 2-functionalized 1,2,3,4-tetrahydroquinolines in the presence of in situ generated catalysts from [Ir(cod)Cl]₂, a bisphosphine, and iodine. The enantioselectivity levels were as high as 96% ee.     

Ruthenium(II) complex catalysts bearing a pyridyl-supported pyrazolyl-imine ligand for transfer hydrogenation of ketones

A new class of hemilabile unsymmetrical 2-(1-arylimino)-6-(pyzazol-1-yl)pyridine ligands and their ruthenium(II) and nickel(II) NNN complexes were synthesized. The Ru(II) complex catalysts have been fully characterized and exhibited good to excellent catalytic activity in the transfer hydrogenation (TH) of ketones in refluxing 2-propanol. These results have demonstrated rare examples of active ruthenium(II) NNN complex catalysts that do not feature a N-H functionality for TH of ketones.