Article
Chemistry, Organic
Viraj A. Bhosale, Martin Nigrini, Martin Dracinsky, Ivana Cisarova, Jan Vesely
Summary: The study presents a versatile method for the synthesis of chiral 2H-1,4-benzoxazines using chiral phosphoric acid catalysis, achieving high yields and enantioselectivity under mild conditions. This strategy expands on traditional methods and provides access to key intermediates for therapeutic candidates, such as prostaglandin D2 receptor antagonists and MI positive allosteric modulator (PAM) compound VU0486846.
Article
Chemistry, Organic
Yuxuan Zhang, Xiaotong Li, Limin Xu, Xiaomin Xie, Yan Lu, Zhaoguo Zhang
Summary: Asymmetric hydrogenation of diaryl 1,4-diketones was achieved using trans-RuCl2[(S)-BINAP)][(S)-Daipen] as the catalyst, affording excellent enantio- and diastereoselectivities (up to >99% ee and de). This procedure provides a convenient and efficient synthetic method for chiral 1,4diarylbutane-1,4-diols, which are important intermediates for a variety of chiral auxiliaries and ligands.
Article
Chemistry, Organic
Yu Nie, Jing Li, Jun Yan, Qianjia Yuan, Wanbin Zhang
Summary: An efficient iridium-catalyzed enantioselective hydrogenation method using iPr-BiphPHOX ligand for 2-alkylidene 1,4-benzoxazin-3-ones was reported, delivering reduced products with excellent yields (up to 99%) and enantioselectivities (up to 99% ee). The reaction worked well on a gram scale with low catalyst loadings and no erosion in enantioselectivity. Additionally, three bioactive molecules can be easily obtained from the reduced products.
Article
Chemistry, Organic
Dongfeng Yang, Chengyi Wang, Yu Wang, Guohua Liu, Tanyu Cheng, Rui Liu
Summary: A new method for the preparation of enantiomerically pure 1,4-oxazines via asymmetric transfer hydrogenation/cyclization enantio-relay process catalyzed by Ru and Au bimetallic catalysts has been developed. The reaction exhibits high stereoselectivity and enriches the understanding of gold catalysis from a mechanistic perspective.
ORGANIC CHEMISTRY FRONTIERS
(2021)
Article
Chemistry, Organic
Chenghao Ye, Feng Gao, Haipeng Wei, Jianzhong Chen, Guoqiang Yang, Qianjia Yuan, Wanbin Zhang
Summary: Enantioselective ring-contraction reaction of 5,6-dihydro-2H-benzo[b][1,4]oxazocines has been successfully developed, providing enantiomerically enriched 3,4-dihydro-2H-1,4-benzoxazine derivatives as single regioisomers with good yields and enantiomeric ratios using an acidic additive. The reaction was performed on a gram scale and the products are easily derivatized.
JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Tianjiao Hu, Lukas Lueckemeier, Constantin Daniliuc, Frank Glorius
Summary: The direct enantioselective hydrogenation of 2-quinolones using Ru(II)-NHC catalyst has been achieved, providing alkyl-, aryl- and halogen-substituted optically active dihydro-2-quinolones in high yields with moderate to excellent enantioselectivities. This reaction presents an efficient and atom-economic pathway to construct simple chiral 3,4-dihydro-2-quinolones.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Applied
Jiayu Zhou, Jianxun Ye, Yang Zhang, Zhaodi Li, Jingjing Li, Delong Liu, Wanbin Zhang
Summary: The RuPHOX-Ru catalyzed asymmetric hydrogenation of diaryl ketones has been developed, yielding chiral diaryl methanols with up to 99% yield and 99% ee. This protocol can be performed on a gram-scale with low catalyst loading (2000 S/C) and the resulting products are valuable for various transformations, especially in the synthesis of chiral drugs like (S)-Orphenadrine and (S)-Neobenodine. Deuterium labeling and control experiments revealed that the RuPHOX-Ru-catalyzed asymmetric hydrogenation is exclusively driven by H-2 as the hydrogen source.
ADVANCED SYNTHESIS & CATALYSIS
(2023)
Article
Chemistry, Organic
Hongyi Zhao, Shengnan Li, Shihao Cheng, Ziyun Lin, Dongfeng Zhang, Haihong Huang
Summary: Various functionalized enantiomerically pure 3-hydroxymethyl-1,4-benzoxazine derivatives, including four stereoisomers, were synthesized from chiral 2,3-epoxy-4-trityloxybutanol using a mild and metal-free method. The mechanism was investigated using online Fourier-transform infrared spectroscopy, revealing a base-promoted cyclization to form intermediates followed by a hydrolysis process. The obtained chiral derivatives showed high stereoselectivity and yield, and were easily derivatized to form unique tricycle-fused benzoxazines.
Article
Chemistry, Multidisciplinary
Zi-Qi Yi, Bo-Wen Deng, Fei Chen, Yan-Mei He, Qing-Hua Fan
Summary: Highly efficient asymmetric hydrogenation of dibenzo[b,f][1,4]oxazepine, dibenzo[b,f][1,4]thiazepine and dibenzo[b,e]azepine derivatives was achieved using chiral cationic ruthenium diamine catalysts, affording diverse chiral seven-membered N-heterocycles with excellent results (up to 99% yield and 99% ee). Additionally, it was observed that the enantioselectivity in the hydrogenation of dibenzo[b,f][1,4]thiazepine and dibenzo[b,e]azepine derivatives could be significantly regulated by the catalyst counteranion.
NEW JOURNAL OF CHEMISTRY
(2023)
Article
Chemistry, Organic
Johal Ruiz, Philippe Oger, Laurent Soulere, Florence Popowycz
Summary: Starting from commercially available (R)- and (S)-beta-citronellol, two strategies were designed to synthesize all four stereoisomers of 2,6-dimethyloctane monoterpene chirons in four or five steps in 32-47% overall yield. Key Ru-catalyzed asymmetric olefin hydrogenation step under moderate conditions allowed the obtainment of desired fragments. DM-SEGPHOS was identified as a economically advantageous alternative to H8-BINAP for equal performances in catalyst screening, opening up new possibilities for versatile and scalable syntheses of these useful building blocks.
JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Physical
Wei Hao, Candice L. Joe, Sloan Ayers, Andrea Daru, Ryan A. Daley, Michal Domanski, Jason S. Chen, Michael A. Schmidt, Donna G. Blackmond
Summary: This study reported a highly efficient and enantioselective asymmetric hydrogenation catalyzed by Ru-DTBM-segphos for a broad range of pyridine-pyrroline trisubstituted alkenes, revealing the reaction mechanism through kinetic, spectroscopic, and computational studies, as well as an intriguing Ru-catalyzed H/D exchange process.
Article
Chemistry, Physical
Wei Hao, Candice L. Joe, Sloan Ayers, Andrea Daru, Ryan A. Daley, Michal Domanski, Jason S. Chen, Michael A. Schmidt, Donna G. Blackmond
Summary: A highly efficient and enantioselective Ru-DTBM-segphos catalyzed asymmetric hydrogenation of pyridine-pyrroline trisubstituted alkenes is reported. Kinetic, spectroscopic, and computational studies suggest that the rate-determining step is the addition of H2, alkene insertion determines the enantioselectivity, and the presence and position of the pyridine nitrogen are critical for enantioselectivity. These studies also reveal a Ru-catalyzed H/D exchange process facilitated by the substrate at room temperature and low pressure, where hydrogenation activity is suppressed. A mechanistic proposal is provided to further define the roles of hydrogen gas, Ru-H species, and protic solvents in this catalytic system.
Article
Chemistry, Physical
Xue-Song Gu, Ying Xiong, Fan Yang, Na Yu, Pu-Cha Yan, Jian-Hua Xie, Qi-Lin Zhou
Summary: An iridium-catalyzed asymmetric hydrogenation method involving dynamic kinetic resolution was successfully developed using chiral spiro PNN-ligands containing a C5-substituted chiral oxazoline unit. This protocol, combined with simple dehydration, provides a straightforward approach to prepare enantiomerically enriched 3-aryloxy tetrahydrofurans, which are prevalent structural motifs in many approved drugs and clinical candidates.
Article
Chemistry, Organic
Martin Nigrini, Viraj A. Bhosale, Ivana Cisarova, Jan Vesely
Summary: In this study, a highly enantioselective desymmetrization of 3-substituted oxetanes was achieved using a confined chiral phosphoric acid as the catalyst. This metal-free process allows for the efficient synthesis of chiral seven-membered 1,4-benzoxazepines with a high degree of enantiocontrol under mild reaction conditions. The developed synthetic strategy demonstrates its synthetic utility in various enantioselective product transformations, proving its effectiveness in diverse scenarios.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Organic
Xiaolei Ji, Chaoren Shen, Xinxin Tian, Kaiwu Dong
Summary: A palladium-catalyzed asymmetric hydroesterification reaction was developed for preparing chiral alpha-substituted succinates with moderate yields and high ee values. The kinetic profile of the reaction progress indicated that the alkene substrate underwent hydroesterification followed by esterification with alcohol. The enantioselectivity was elucidated by density functional theory computation.
