Search Results
Efficient methylation of anilines with methanol catalysed by cyclometalated ruthenium complexes
2021, Piehl, Patrick, Amuso, Roberta, Spannenberg, Anke, Gabriele, Bartolo, Neumann, Helfried, Beller, Matthias
Cyclometalated ruthenium complexes4-10allow the effective methylation of anilines with methanol to selectively giveN-methylanilines. This hydrogen autotransfer procedure proceeds under mild conditions (60 °C) in a practical manner (NaOH as base). Mechanistic investigations suggest an active homogenous ruthenium complex and β-hydride elimination of methanol as the rate determining step. © The Royal Society of Chemistry 2021.
Activation of perfluoroalkyl iodides by anions: extending the scope of halogen bond activation to C(sp3)-H amidation, C(sp2)-H iodination, and perfluoroalkylation reactions
2023, Wang, Yaxin, Cao, Zehui, He, Qin, Huang, Xin, Liu, Jiaxi, Neumann, Helfried, Chen, Gong, Beller, Matthias
A simple, efficient, and convenient activation of perfluoroalkyl iodides by tBuONa or KOH, without expensive photo- or transition metal catalysts, allows the promotion of versatile a-sp3 C-H amidation reactions of alkyl ethers and benzylic hydrocarbons, C-H iodination of heteroaryl compounds, and perfluoroalkylations of electron-rich p bonds. Mechanistic studies show that these novel protocols are based on the halogen bond interaction between perfluoroalkyl iodides and tBuONa or KOH, which promote homolysis of perfluoroalkyl iodides under mild conditions.
A general strategy for the synthesis of α-trifluoromethyl- and α-perfluoroalkyl-β-lactams via palladium-catalyzed carbonylation
2021, Li, Yang, Zhang, Cai-Lin, Huang, Wei-Heng, Sun, Ning, Hao, Meng, Neumann, Helfried, Beller, Matthias
β-Lactam compounds play a key role in medicinal chemistry, specifically as the most important class of antibiotics. Here, we report a novel one-step approach for the synthesis of α-(trifluoromethyl)-β-lactams and related products from fluorinated olefins, anilines and CO. Utilization of an advanced palladium catalyst system with the Ruphos ligand allows for selective cycloaminocarbonylations to give diverse fluorinated β-lactams in high yields. © The Royal Society of Chemistry 2021.
Simple ruthenium-catalyzed reductive amination enables the synthesis of a broad range of primary amines
2018, Senthamarai, Thirusangumurugan, Murugesan, Kathiravan, Schneidewind, Jacob, Kalevaru, Narayana V., Baumann, Wolfgang, Neumann, Helfried, Kamer, Paul C. J., Beller, Matthias, Jagadeesh, Rajenahally V.
The production of primary benzylic and aliphatic amines, which represent essential feedstocks and key intermediates for valuable chemicals, life science molecules and materials, is of central importance. Here, we report the synthesis of this class of amines starting from carbonyl compounds and ammonia by Ru-catalyzed reductive amination using H2. Key to success for this synthesis is the use of a simple RuCl2(PPh3)3 catalyst that empowers the synthesis of >90 various linear and branched benzylic, heterocyclic, and aliphatic amines under industrially viable and scalable conditions. Applying this catalyst, −NH2 moiety has been introduced in functionalized and structurally diverse compounds, steroid derivatives and pharmaceuticals. Noteworthy, the synthetic utility of this Ru-catalyzed amination protocol has been demonstrated by upscaling the reactions up to 10 gram-scale syntheses. Furthermore, in situ NMR studies were performed for the identification of active catalytic species. Based on these studies a mechanism for Ru-catalyzed reductive amination is proposed.
Cyclometalated Ruthenium Pincer Complexes as Catalysts for the α-Alkylation of Ketones with Alcohols
2020, Piehl, Patrick, Amuso, Roberta, Alberico, Elisabetta, Junge, Henrik, Gabriele, Bartolo, Neumann, Helfried, Beller, Matthias
Ruthenium PNP pincer complexes bearing supplementary cyclometalated C,N-bound ligands have been prepared and fully characterized for the first time. By replacing CO and H− as ancillary ligands in such complexes, additional electronic and steric modifications of this topical class of catalysts are possible. The advantages of the new catalysts are demonstrated in the general α-alkylation of ketones with alcohols following a hydrogen autotransfer protocol. Herein, various aliphatic and benzylic alcohols were applied as green alkylating agents for ketones bearing aromatic, heteroaromatic or aliphatic substituents as well as cyclic ones. Mechanistic investigations revealed that during catalysis, Ru carboxylate complexes are predominantly formed whereas neither the PNP nor the CN ligand are released from the catalyst in significant amounts. © 2020 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.
Cooperative catalytic methoxycarbonylation of alkenes: Uncovering the role of palladium complexes with hemilabile ligands
2018, Dong, Kaiwu, Sang, Rui, Wei, Zhihong, Liu, Jie, Dühren, Ricarda, Spannenberg, Anke, Jiao, Haijun, Neumann, Helfried, Jackstell, Ralf, Franke, Robert, Beller, Matthias
Mechanistic studies of the catalyst [Pd2(dba)3/1,1′-bis(tert-butyl(pyridin-2-yl)phosphanyl)ferrocene, L2] for olefin alkoxycarbonylation reactions are described. X-ray crystallography reveals the coordination of the pyridyl nitrogen atom in L2 to the palladium center of the catalytic intermediates. DFT calculations on the elementary steps of the industrially relevant carbonylation of ethylene (the Lucite α-process) indicate that the protonated pyridyl moiety is formed immediately, which facilitates the formation of the active palladium hydride complex. The insertion of ethylene and CO into this intermediate leads to the corresponding palladium acyl species, which is kinetically reversible. Notably, this key species is stabilized by the hemilabile coordination of the pyridyl nitrogen atom in L2. The rate-determining alcoholysis of the acyl palladium complex is substantially facilitated by metal-ligand cooperation. Specifically, the deprotonation of the alcohol by the built-in base of the ligand allows a facile intramolecular nucleophilic attack on the acyl palladium species concertedly. Kinetic measurements support this mechanistic proposal and show that the rate of the carbonylation step is zero-order dependent on ethylene and CO. Comparing CH3OD and CH3OH as nucleophiles suggests the involvement of (de)protonation in the rate-determining step.
3,3-Difluoroallyl ammonium salts: highly versatile, stable and selective gem-difluoroallylation reagents
2021, Ye, Fei, Ge, Yao, Spannenberg, Anke, Neumann, Helfried, Xu, Li-Wen, Beller, Matthias
The selective synthesis of fluorinated organic molecules continues to be of major importance for the development of bioactive compounds (agrochemicals and pharmaceuticals) as well as unique materials. Among the established synthetic toolbox for incorporation of fluorine-containing units, efficient and general reagents for introducing -CF2- groups have been largely neglected. Here, we present the synthesis of 3,3-difluoropropen-1-yl ammonium salts (DFPAs) as stable, and scalable gem-difluoromethylation reagents, which allow for the direct reaction with a wide range of fascinating nucleophiles. DFPAs smoothly react with N-, O-, S-, Se-, and C-nucleophiles under mild conditions without necessity of metal catalysts with exclusive regioselectivity. In this way, the presented reagents also permit the straightforward preparation of many analogues of existing pharmaceuticals.
Ruthenium-Catalyzed Site-Selective Trifluoromethylations and (Per)Fluoroalkylations of Anilines and Indoles
2020, Li, Yang, Neumann, Helfried, Beller, Matthias
Introducing (per)fluoroalkyl groups into arenes continues to be an interesting, but challenging area in organofluorine chemistry. We herein report an ortho-selective C−H perfluoroalkylation including trifluoromethylations of anilines and indoles without the need of protecting groups using RfI and RfBr as commercially available reagents. The availability and price of the starting materials and the inherent selectivity make this novel methodology attractive for the synthesis of diverse (per)fluoroalkylated building blocks, for example, for bioactive compounds and materials. © 2020 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.
Manganese-catalyzed selective C–H activation and deuteration by means of a catalytic transient directing group strategy
2021, Kopf, Sara, Neumann, Helfried, Beller, Matthias
A novel manganese-catalyzed C-H activation methodology for selective hydrogen isotope exchange of benzaldehydes is presented. Using D2O as a cheap and convenient source of deuterium, the reaction proceeds with excellent functional group tolerance. Highortho-selectivity is achieved in the presence of catalytic amounts of specific amines, whichin situform a transient directing group. © The Royal Society of Chemistry 2021.
Homogeneous cobalt-catalyzed reductive amination for synthesis of functionalized primary amines
2019, Murugesan, Kathiravan, Wei, Zhihong, Chandrashekhar, Vishwas G., Neumann, Helfried, Spannenberg, Anke, Jiao, Haijun, Beller, Matthias, Jagadeesh, Rajenahally V.
The development of earth abundant 3d metal-based catalysts continues to be an important goal of chemical research. In particular, the design of base metal complexes for reductive amination to produce primary amines remains as challenging. Here, we report the combination of cobalt and linear-triphos (bis(2-diphenylphosphinoethyl)phenylphosphine) as the molecularly-defined non-noble metal catalyst for the synthesis of linear and branched benzylic, heterocyclic and aliphatic primary amines from carbonyl compounds, gaseous ammonia and hydrogen in good to excellent yields. Noteworthy, this cobalt catalyst exhibits high selectivity and as a result the -NH2 moiety is introduced in functionalized and structurally diverse molecules. An inner-sphere mechanism on the basis of the mono-cationic [triphos-CoH]+ complex as active catalyst is proposed and supported with density functional theory computation on the doublet state potential free energy surface and H2 metathesis is found as the rate-determining step.