- Zinc-Catalyzed Asymmetric Hydrosilylation of Cyclic Imines: Synthesis of Chiral 2-Aryl-Substituted Pyrrolidines as Pharmaceutical Building Blocks
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The first successful enantioselective hydrosilylation of cyclic imines promoted by a chiral zinc complex is reported. In situ generated zinc-ProPhenol complex with silane afforded pharmaceutically relevant enantioenriched 2-aryl-substituted pyrrolidines in high yields and with excellent enantioselectivities (up to 99% ee). The synthetic utility of presented methodology is demonstrated in an efficient synthesis of the corresponding chiral cyclic amines, being pharmaceutical drug precursors to the Aticaprant and Larotrectinib. (Figure presented.).
- W?glarz, Izabela,Michalak, Karol,Mlynarski, Jacek
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supporting information
p. 1317 - 1321
(2020/12/09)
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- α,α′-C-H Bond Difunctionalization of Unprotected Alicyclic Amines
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A simple one-pot procedure enables the sequential, regioselective, and diastereoselective introduction of the same or two different substituents to the α- and α′-positions of unprotected azacycles. Aryl, alkyl, and alkenyl substituents are introduced via their corresponding organolithium compounds. The scope of this transformation includes pyrrolidines, piperidines, azepanes, and piperazines.
- Valles, Daniel A.,Dutta, Subhradeep,Paul, Anirudra,Abboud, Khalil A.,Ghiviriga, Ion,Seidel, Daniel
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supporting information
p. 6367 - 6371
(2021/08/18)
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- Enantioselective Synthesis of 2-Substituted Pyrrolidines via Intramolecular Reductive Amination
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Catalyzed by the complex generated in situ from iridium and the chiral ferrocene ligand, tert -butyl (4-oxo-4-arylbutyl)carbamate substrates were deprotected and then reductively cyclised to form 2-substituted arylpyrrolidines in a one-pot manner, in which the intramolecular reductive amination was the key step. A range of chiral 2-substituted arylpyrrolidines were synthesised in up to 98percent yield and 92percent ee.
- Chang, Mingxin,Guo, Haodong,Huang, Haizhou,Zhang, Tao,Zhao, Wenlei,Zhou, Huan
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p. 2713 - 2719
(2019/06/19)
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- Direct α-C-H bond functionalization of unprotected cyclic amines
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Cyclic amines are ubiquitous core structures of bioactive natural products and pharmaceutical drugs. Although the site-selective abstraction of C-H bonds is an attractive strategy for preparing valuable functionalized amines from their readily available parent heterocycles, this approach has largely been limited to substrates that require protection of the amine nitrogen atom. In addition, most methods rely on transition metals and are incompatible with the presence of amine N-H bonds. Here we introduce a protecting-group-free approach for the α-functionalization of cyclic secondary amines. An operationally simple one-pot procedure generates products via a process that involves intermolecular hydride transfer to generate an imine intermediate that is subsequently captured by a nucleophile, such as an alkyl or aryl lithium compound. Reactions are regioselective and stereospecific and enable the rapid preparation of bioactive amines, as exemplified by the facile synthesis of anabasine and (-)-solenopsin A.
- Chen, Weijie,Ma, Longle,Paul, Anirudra,Seidel, Daniel
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p. 165 - 169
(2018/02/06)
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- Synthesis of chiral cyclic amines via Ir-catalyzed enantioselective hydrogenation of cyclic imines
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A highly enantioselective hydrogenation of cyclic imines for synthesis of chiral cyclic amines has been realized. With the complex of iridium and (R,R)-f-spiroPhos as the catalyst, a range of cyclic 2-aryl imines were smoothly hydrogenated under mild conditions without any additive to provide the corresponding chiral cyclic amines with excellent enantioselectivities of up to 98% ee. Moreover, this method could be successfully applied to the synthesis of (+)-(6S,10bR)-McN-4612-Z.
- Zhang, Ying,Kong, Duanyang,Wang, Rui,Hou, Guohua
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p. 3006 - 3012
(2017/04/11)
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- Enantioselective Direct Synthesis of Free Cyclic Amines via Intramolecular Reductive Amination
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Chiral cyclic amines can be prepared via intramolecular reductive amination of N-Boc-protected amino ketones in a one-pot process. With the complex of iridium and f-spiroPhos as the catalyst, a range of N-Boc-protected amino ketones are smoothly transformed into chiral cyclic free amines in high yields and excellent enantioselectivities (up to 97% ee). Moreover, this method can also be successfully applied to the synthesis of a κ-opioid receptor selective antagonist, (S)-1.
- Zhang, Ying,Yan, Qiaozhi,Zi, Guofu,Hou, Guohua
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p. 4215 - 4218
(2017/08/23)
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- Design, synthesis and biological evaluation of aminobenzyloxyarylamide derivatives as selective κ opioid receptor antagonists
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Opioid receptors play an important role in both behavioral and mood functions. Based on the structural modification of LY2456302, a series of aminobenzyloxyarylamide derivatives were designed and synthesized as κ opioid receptor antagonists. The κ opioid receptor binding ability of these compounds were evaluated with opioid receptors binding assays. Compounds 1a-d showed high affinity for κ opioid receptor. Especially for compound 1c, exhibited a significant Kivalue of 15.7?nM for κ opioid receptor binding and a higher selectivity over μ and δ opioid receptors compared to (±)LY2456302. In addition, compound 1c also showed potent κ antagonist activity with κ IC50?=?9.32?nM in [35S]GTP-γ-S functional assay. The potential use of the representative compounds as antidepressants was also investigated. The most potent compound 1c not only exhibited potent antidepressant activity in the mice forced swimming test, but also displayed the effect of anti-anxiety in the elevated plus-maze test.
- Wang, Junwei,Song, Qiao,Xu, Anhua,Bao, Yu,Xu, Yungen,Zhu, Qihua
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- AROMATIC HETEROCYCLIC DERIVATIVE AND PHARMACEUTICAL
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The main purpose of the invention is to provide a novel aromatic heterocyclic derivative or a pharmaceutically acceptable salt thereof. Examples of the invention include aromatic heterocyclic derivatives represented by general formula [1] and pharmaceutically acceptable salts thereof. In formula [1], R1 represents phenyl optionally substituted with one or two groups selected from the group consisting of halogens ,as well as alkyls and alkoxys optionally substituted by halogens; R2 represents a hydrogen, an alkyl, cycloalkyl, or alkoxy optionally substituted by a halogen, or a heteroaryl optionally substituted by an alkyl; X represents CR3, and Y represents N or CR4, or X represents N, and Y represents CR4; and Z represents CR5 or N.
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Paragraph 0118; 0120
(2015/04/15)
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- Iridium-catalyzed enantioselective hydrogenation of cyclic imines
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A catalytic complex made from [Ir(COD)Cl]2 [di-μ-chloro- bis(1,5-cyclooctadiene)diiridium(I)] precursor and (S,S)-f-Binaphane ((R,R)-1,1′-bis{(R)-4,5-dihydro-3H-dinaphtho[1,2-c:2′,1′-e] phosphepino}ferrocene) ligand effectively catalyzed the en
- Chang, Mingxin,Li, Wei,Hou, Guohua,Zhang, Xumu
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supporting information; experimental part
p. 3121 - 3125
(2011/02/22)
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