140632-19-5Relevant articles and documents
Catalytic enantioselective synthesis of β-amino alcohols by nitrene insertion
Zhou, Zijun,Tan, Yuqi,Shen, Xiang,Ivlev, Sergei,Meggers, Eric
, p. 452 - 458 (2020/12/31)
Chiral β-amino alcohols are important building blocks for the synthesis of drugs, natural products, chiral auxiliaries, chiral ligands and chiral organocatalysts. The catalytic asymmetric β-amination of alcohols offers a direct strategy to access this class of molecules. Herein, we report a general intramolecular C(sp3)-H nitrene insertion method for the synthesis of chiral oxazolidin-2-ones as precursors of chiral β-amino alcohols. Specifically, the ring-closing C(sp3)-H amination of N-benzoyloxycarbamates with 2 mol% of a chiral ruthenium catalyst provides cyclic carbamates in up to 99% yield and with up to 99% ee. The method is applicable to benzylic, allylic, and propargylic C-H bonds and can even be applied to completely non-activated C (sp3)-H bonds, although with somewhat reduced yields and stereoselectivities. The obtained cyclic carbamates can subsequently be hydrolyzed to obtain chiral β-amino alcohols. The method is very practical as the catalyst can be easily synthesized on a gram scale and can be recycled after the reaction for further use. The synthetic value of the new method is demonstrated with the asymmetric synthesis of a chiral oxazolidin-2-one as intermediate for the synthesis of the natural product aurantioclavine and chiral β-amino alcohols that are intermediates for the synthesis of chiral amino acids, indane-derived chiral Box-ligands, and the natural products dihydrohamacanthin A and dragmacidin A.[Figure not available: see fulltext.].
Enantioselective Cascade Biocatalysis for Deracemization of Racemic β-Amino Alcohols to Enantiopure (S)-β-Amino Alcohols by Employing Cyclohexylamine Oxidase and ω-Transaminase
Zhang, Jian-Dong,Chang, Ya-Wen,Dong, Rui,Yang, Xiao-Xiao,Gao, Li-Li,Li, Jing,Huang, Shuang-Ping,Guo, Xing-Mei,Zhang, Chao-Feng,Chang, Hong-Hong
, p. 124 - 128 (2020/09/21)
Optically active β-amino alcohols are very useful chiral intermediates frequently used in the preparation of pharmaceutically active substances. Here, a novel cyclohexylamine oxidase (ArCHAO) was identified from the genome sequence of Arthrobacter sp. TYUT010-15 with the R-stereoselective deamination activity of β-amino alcohol. ArCHAO was cloned and successfully expressed in E. coli BL21, purified and characterized. Substrate-specific analysis revealed that ArCHAO has high activity (4.15 to 6.34 U mg?1 protein) and excellent enantioselectivity toward the tested β-amino alcohols. By using purified ArCHAO, a wide range of racemic β-amino alcohols were resolved, (S)-β-amino alcohols were obtained in >99 % ee. Deracemization of racemic β-amino alcohols was conducted by ArCHAO-catalyzed enantioselective deamination and transaminase-catalyzed enantioselective amination to afford (S)-β-amino alcohols in excellent conversion (78–94 %) and enantiomeric excess (>99 %). Preparative-scale deracemization was carried out with 50 mM (6.859 g L?1) racemic 2-amino-2-phenylethanol, (S)-2-amino-2-phenylethanol was obtained in 75 % isolated yield and >99 % ee.
Efficient diastereoselective synthesis of cis-2-amino-1-indanol derivatives and cis- and trans-1-amino-2-indanol via Pd-catalyzed hydrogenation
Nguyen, Thi Ha,Ma, Eunsook
supporting information, p. 3717 - 3728 (2021/11/01)
(±)-cis-2-amino-1-indanol was diastereoselectively synthesized from 1,2-indanedion-2-oxime in ethanol at 25 °C under 10% Pd/C-catalyzed hydrogenation conditions. Under the same hydrogenation condition, 1,2-indanedion-2-oxime and their derivatives having one and/or two electron-donating groups in aliphatic or aromatic part of indanyl ring were diastereoselectively reduced to racemic cis-2-amino-1-indanol derivatives. From 1,2-indanedion-1-oxime, (±)-trans-1-amino-2-indanol was obtained in ethanol at 25 °C over a 10% Pd/BaSO4 catalyst. In contrast, the 10% Pd/BaSO4-catalyzed hydrogenation reaction in ethanol at 45 °C afforded cis-1-hydroxyamino-2-indanol from 1,2-indanedion-1-oxime, followed by reduction to form (±)-cis-1-amino-2-indanol. The diastereoselectivity of β-aminoindanols was dependent on the Pd catalyst, reaction temperature, and pH of the reaction medium.
Site-Specific C(sp3)–H Aminations of Imidates and Amidines Enabled by Covalently Tethered Distonic Radical Anions
Fang, Yuanding,Fu, Kang,Shi, Lei,Zhao, Rong,Zhou, Jia
, p. 20682 - 20690 (2020/09/07)
The utilization of N-centered radicals to synthesize nitrogen-containing compounds has attracted considerable attention recently, due to their powerful reactivities and the concomitant construction of C?N bonds. However, the generation and control of N-centered radicals remain particularly challenging. We report a tethering strategy using SOMO-HOMO-converted distonic radical anions for the site-specific aminations of imidates and amidines with aid of the non-covalent interaction. This reaction features a remarkably broad substrate scope and also enables the late-stage functionalization of bioactive molecules. Furthermore, the reaction mechanism is thoroughly investigated through kinetic studies, Raman spectroscopy, electron paramagnetic resonance spectroscopy, and density functional theory calculations, revealing that the aminations likely involve direct homolytic cleavage of N?H bonds and subsequently controllable 1,5 or 1,6 hydrogen atom transfer.
Visible-Light-Driven N-Heterocyclic Carbene Catalyzed γ- and ?-Alkylation with Alkyl Radicals
Dai, Lei,Xia, Zi-Hao,Gao, Yuan-Yuan,Gao, Zhong-Hua,Ye, Song
supporting information, p. 18124 - 18130 (2019/11/13)
The merging of photoredox catalysis and N-heterocyclic carbene (NHC) catalysis for γ- and ?-alkylation of enals with alkyl radicals was developed. The alkylation reaction of γ-oxidized enals with alkyl halides worked well for the synthesis γ-multisubstituted-α,β-unsaturated esters, including those with challenging vicinal all-carbon quaternary centers. The synthesis of ?-multisubstituted-α,β-γ,δ-diunsaturated esters by an unprecedented NHC-catalyzed ?-functionalization was also established.
Catalytic β C-H amination: Via an imidate radical relay
Stateman, Leah M.,Wappes, Ethan A.,Nakafuku, Kohki M.,Edwards, Kara M.,Nagib, David A.
, p. 2693 - 2699 (2019/03/06)
The first catalytic strategy to harness imidate radicals for C-H functionalization has been developed. This iodine-catalyzed approach enables β C-H amination of alcohols by an imidate-mediated radical relay. In contrast to our first-generation, (super)stoichiometric protocol, this catalytic method enables faster and more efficient reactivity. Furthermore, lower oxidant concentration affords broader functional group tolerance, including alkenes, alkynes, alcohols, carbonyls, and heteroarenes. Mechanistic experiments interrogating the electronic nature of the key 1,5 H-atom transfer event are included, as well as probes for chemo-, regio-, and stereo-selectivity.
Anti-HIV medicine containing indinavir and preparation method thereof
-
, (2018/08/28)
The invention discloses anti-HIV medicine containing indinavir and a preparation method thereof. The anti-HIV medicine containing indinavir is prepared from indinavir and pharmaceutically acceptable carriers, wherein the chemical name of indinavir is (1(1S,2R),5(S))-2,3,5-tri-deoxy-N-(2,3-dihydro-2-hydroxyl-1H-indene-1-yl)-5-[2-[[(1,1-dimethyl ethyl) amino]carbonyl]-4-(3-picolyl)-1-piperazinyl]-2-(benzyl)-D-erythro-valeramide. The process of a preparation process is simple and compact; the raw materials can be easily obtained; economic performance and environment protection are realized; the industrialization can be favorably realized; the economic technology development of the indinavir raw medicine of the anti-HIV medicine can be promoted; the dissolving-out degree of the anti-HIV medicine containing indinavir is high; the effect is ideal; the medicine is suitable for mass production.
Highly Efficient and Robust Enantioselective Liquid–Liquid Extraction of 1,2-Amino Alcohols utilizing VAPOL- and VANOL-based Phosphoric Acid Hosts
Pinxterhuis, Erik B.,Gualtierotti, Jean-Baptiste,Wezenberg, Sander J.,de Vries, Johannes G.,Feringa, Ben L.
, p. 178 - 184 (2017/12/15)
The large-scale production of enantiopure compounds in a cost-effective and environmentally friendly manner remains one of the major challenges of modern-day chemistry. The resolution of racemates through enantioselective liquid–liquid extraction was developed as a suitable solution but has remained largely underused, owing to a lack of highly efficient and robust chiral hosts to mediate the process. This paucity of hosts can in part be attributed to a poor understanding of the underlying principles behind these processes hindering the design of more efficient selectors. A previously untested class of hosts, VAPOL and VANOL derived phosphoric acids, has been studied in depth for the efficient enantioselective liquid–liquid extraction of 1,2-amino alcohols. A systematic investigation of extraction parameters was conducted, revealing many key interactions and DFT calculations illustrate the binding modes for the 1:1 complexes that are involved in chiral recognition. The resulting, now-optimized, procedures are highly robust and easy to implement. They are also easily scalable, as demonstrated by U-tube experiments.
Radical-mediated intramolecular β-C(sp3)-H amidation of alkylimidates: Facile synthesis of 1,2-amino alcohols
Mou, Xue-Qing,Chen, Xiang-Yu,Chen, Gong,He, Gang
, p. 515 - 518 (2018/01/19)
A new radical-mediated intramolecular β-C(sp3)-H amidation reaction of O-alkyl trichloro- or arylimidates is reported. Various oxazolines were efficiently prepared from easily accessible alcohol starting materials. The trichloro-oxazoline products can be hydrolyzed under mild conditions to give valuable 1,2-amino alcohols. This amidation reaction exhibits a broad substrate scope and good functional group tolerance, and offers a powerful means for the C(sp3)-H functionalization of alcohols. Mechanistic studies suggest that a sequence of 1,5-HAT of an imidate radical, iodination and cyclization might be operative.
Directed β C-H Amination of Alcohols via Radical Relay Chaperones
Wappes, Ethan A.,Nakafuku, Kohki M.,Nagib, David A.
, p. 10204 - 10207 (2017/08/10)
A radical-mediated strategy for β C-H amination of alcohols has been developed. This approach employs a radical relay chaperone, which serves as a traceless director that facilitates selective C-H functionalization via 1,5-hydrogen atom transfer (HAT) and enables net incorporation of ammonia at the β carbon of alcohols. The chaperones presented herein enable direct access to imidate radicals, allowing their first use for H atom abstraction. A streamlined protocol enables rapid conversion of alcohols to their β-amino analogs (via in situ conversion of alcohols to imidates, directed C-H amination, and hydrolysis to NH2). Mechanistic experiments indicate HAT is rate-limiting, whereas intramolecular amination is product- and stereo-determining.
