180272-45-1Relevant academic research and scientific papers
Low-Temperature Nickel-Catalyzed C?N Cross-Coupling via Kinetic Resolution Enabled by a Bulky and Flexible Chiral N-Heterocyclic Carbene Ligand
Hong, Xin,Shi, Shi-Liang,Wang, Zi-Chao,Xie, Pei-Pei,Xu, Youjun
supporting information, p. 16077 - 16084 (2021/06/17)
The transition-metal-catalyzed C?N cross-coupling has revolutionized the construction of amines. Despite the innovations of multiple generations of ligands to modulate the reactivity of the metal center, ligands for the low-temperature enantioselective amination of aryl halides remain a coveted target of catalyst engineering. Designs that promote one elementary reaction often create bottlenecks at other steps. We here report an unprecedented low-temperature (as low as ?50 °C), enantioselective Ni-catalyzed C?N cross-coupling of aryl chlorides with sterically hindered secondary amines via a kinetic resolution process (s factor up to >300). A bulky yet flexible chiral N-heterocyclic carbene (NHC) ligand is leveraged to drive both oxidative addition and reductive elimination with low barriers and control the enantioselectivity. Computational studies indicate that the rotations of multiple σ-bonds on the C2-symmetric chiral ligand adapt to the changing needs of catalytic processes. We expect this design would be widely applicable to diverse transition states to achieve other challenging metal-catalyzed asymmetric cross-coupling reactions.
Asymmetric Transfer Hydrogenation of Unhindered and Non-Electron-Rich 1-Aryl Dihydroisoquinolines with High Enantioselectivity
Barrios-Rivera, Jonathan,Xu, Yingjian,Wills, Martin
supporting information, p. 6283 - 6287 (2020/09/02)
The use of arene/Ru/TsDPEN catalysts bearing a heterocyclic group on the TsDPEN in the asymmetric transfer hydrogenation (ATH) of dihydroisoquinolines (DHIQs) containing meta- or para-substituted aromatic groups at the 1-position results in the formation of products of high enantiomeric excess. Previously, only 1-(ortho-substituted)aryl DHIQs, or with an electron-rich fused ring gave products with high enantioselectivity; therefore, this approach solves a long-standing challenge for imine ATH.
Josiphos-Type Binaphane Ligands for Iridium-Catalyzed Enantioselective Hydrogenation of 1-Aryl-Substituted Dihydroisoquinolines
Nie, Huifang,Zhu, Yupu,Hu, Xiaomu,Wei, Zhao,Yao, Lin,Zhou, Gang,Wang, Pingan,Jiang, Ru,Zhang, Shengyong
supporting information, p. 8641 - 8645 (2019/10/17)
Convenient synthesis and useful application of a series of Josiphos-type binaphane ligands were described. The iridium complexes of these chiral diphosphines displayed excellent enantioselectivity and good reactivity in the asymmetric hydrogenation of challenging 1-aryl-substituted dihydroisoquinoline substrates (full conversions, up to >99% ee, 4000 TON). The use of 40% HBr (aqueous solution) as an additive dramatically improved the asymmetric induction of these catalysts. This transformation provided a highly efficient and enantioselective access to chiral 1-aryl-substituted tetrahydroisoquinolines, which were of great importance and common in natural products and biologically active molecules.
Breaking Symmetry: Engineering Single-Chain Dimeric Streptavidin as Host for Artificial Metalloenzymes
Wu, Shuke,Zhou, Yi,Rebelein, Johannes G.,Kuhn, Miriam,Mallin, Hendrik,Zhao, Jingming,Igareta, Nico V.,Ward, Thomas R.
supporting information, p. 15869 - 15878 (2019/10/11)
The biotin-streptavidin technology has been extensively exploited to engineer artificial metalloenzymes (ArMs) that catalyze a dozen different reactions. Despite its versatility, the homotetrameric nature of streptavidin (Sav) and the noncooperative binding of biotinylated cofactors impose two limitations on the genetic optimization of ArMs: (i) point mutations are reflected in all four subunits of Sav, and (ii) the noncooperative binding of biotinylated cofactors to Sav may lead to an erosion in the catalytic performance, depending on the cofactor:biotin-binding site ratio. To address these challenges, we report on our efforts to engineer a (monovalent) single-chain dimeric streptavidin (scdSav) as scaffold for Sav-based ArMs. The versatility of scdSav as host protein is highlighted for the asymmetric transfer hydrogenation of prochiral imines using [Cp*Ir(biot-p-L)Cl] as cofactor. By capitalizing on a more precise genetic fine-tuning of the biotin-binding vestibule, unrivaled levels of activity and selectivity were achieved for the reduction of challenging prochiral imines. Comparison of the saturation kinetic data and X-ray structures of [Cp*Ir(biot-p-L)Cl]·scdSav with a structurally related [Cp*Ir(biot-p-L)Cl]·monovalent scdSav highlights the advantages of the presence of a single biotinylated cofactor precisely localized within the biotin-binding vestibule of the monovalent scdSav. The practicality of scdSav-based ArMs was illustrated for the reduction of the salsolidine precursor (500 mM) to afford (R)-salsolidine in 90% ee and >17 ?000 TONs. Monovalent scdSav thus provides a versatile scaffold to evolve more efficient ArMs for in vivo catalysis and large-scale applications.
Asymmetric Transfer Hydrogenation in Thermomorphic Microemulsions Based on Ionic Liquids
Hejazifar, Mahtab,Pálv?lgyi, ádám Márk,Bitai, Jacqueline,Lanaridi, Olga,Bica-Schr?der, Katharina
, p. 1841 - 1851 (2019/10/11)
A thermomorphic ionic-liquid-based microemulsion system was successfully applied for the Ru-catalyzed asymmetric transfer hydrogenation of ketones. On the basis of the temperature-dependent multiphase behavior of the targeted microemulsion, simple product separation as well as catalyst recycling could be realized. The use of water-soluble ligands improved the immobilization of the catalyst in the microemulsion phase and significantly decreased the catalyst leaching into the organic layer upon extraction of the product. Eventually, the optimized microemulsion system could be applied to a wide range of aromatic ketones that were reduced with good isolated yields (up to 98%) and enantioselectivities (up to 97%), while aliphatic ketones were less successful.
A through halogen bond activation isoquinoline asymmetric hydrogenation method
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Paragraph 0031-0040; 0062, (2019/03/26)
A through halogen bond activation isoquinoline asymmetric hydrogenation method, the catalyzing system is [...] complex, the activator is a halide. The reaction can be carried out under the following conditions, temperature: 25 - 100 °C; solvent: tetrahydr
Dual Stereocontrol for Enantioselective Hydrogenation of Dihydroisoquinolines Induced by Tuning the Amount of N-Bromosuccinimide
Ji, Yue,Wang, Jie,Chen, Muwang,Shi, Lei,Zhou, Yonggui
supporting information, p. 139 - 142 (2018/01/05)
An efficient dual stereocontrol in iridium-catalyzed hydrogenation of 1-substituted 3,4-dihydroisoquinolines was realized by tuning the amount of N-bromosuccinimide using chiral ligand of single configuration, providing both enantiomers of 1-substituted 1,2,3,4-tetrahydroisoquinolines with up to 89% ee (S) and 98% ee (R), respectively. Dual activation role of N-bromosuccinimide is proposed to be responsible for the reversal of enantioselectivity under two hydrogenation conditions.
Directed Evolution of an Artificial Imine Reductase
Hestericová, Martina,Heinisch, Tillman,Alonso-Cotchico, Lur,Maréchal, Jean-Didier,Vidossich, Pietro,Ward, Thomas R.
supporting information, p. 1863 - 1868 (2018/01/27)
Artificial metalloenzymes, resulting from incorporation of a metal cofactor within a host protein, have received increasing attention in the last decade. The directed evolution is presented of an artificial transfer hydrogenase (ATHase) based on the biotin-streptavidin technology using a straightforward procedure allowing screening in cell-free extracts. Two streptavidin isoforms were yielded with improved catalytic activity and selectivity for the reduction of cyclic imines. The evolved ATHases were stable under biphasic catalytic conditions. The X-ray structure analysis reveals that introducing bulky residues within the active site results in flexibility changes of the cofactor, thus increasing exposure of the metal to the protein surface and leading to a reversal of enantioselectivity. This hypothesis was confirmed by a multiscale approach based mostly on molecular dynamics and protein–ligand dockings.
A method catalyzed by iridium and used for bidirectional enantioselective synthesis of chiral tetrahydroisoquinoline
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Paragraph 0035-0041, (2018/03/01)
A method catalyzed by iridium and used for bidirectional enantioselective synthesis of chiral tetrahydroisoquinoline is provided. A catalysis system adopted by the method is a chiral diphosphine complex of iridium. By utilizing a single chiral source and
Directed evolution of artificial metalloenzymes: Genetic optimization of the catalytic activity
Hestericová, Martina
, p. 189 - 192 (2018/05/22)
Artificial metalloenzymes (ArMs) based on the incorporation of a biotinylated metal cofactor within a streptavidin (Sav) combine attractive features of both enzymatic and homogeneous catalysis. To speed up their optimization, we present a directed evolution of an artificial transfer hydrogenase (ATHase) based on a streamlined and optimized protocol for the design, overexpression and screening of Sav isoforms. Ten positions have been subjected to mutagenesis to yield two variants with improved catalytic activity and selectivity for the reduction of cyclic imines, along with greater stability in a biphasic medium.
