- Enantioconvergent Cu-Catalyzed Radical C-N Coupling of Racemic Secondary Alkyl Halides to Access α-Chiral Primary Amines
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α-Chiral alkyl primary amines are virtually universal synthetic precursors for all other α-chiral N-containing compounds ubiquitous in biological, pharmaceutical, and material sciences. The enantioselective amination of common alkyl halides with ammonia is appealing for potential rapid access to α-chiral primary amines, but has hitherto remained rare due to the multifaceted difficulties in using ammonia and the underdeveloped C(sp3)-N coupling. Here we demonstrate sulfoximines as excellent ammonia surrogates for enantioconvergent radical C-N coupling with diverse racemic secondary alkyl halides (>60 examples) by copper catalysis under mild thermal conditions. The reaction efficiently provides highly enantioenrichedN-alkyl sulfoximines (up to 99% yield and >99% ee) featuring secondary benzyl, propargyl, α-carbonyl alkyl, and α-cyano alkyl stereocenters. In addition, we have converted the masked α-chiral primary amines thus obtained to various synthetic building blocks, ligands, and drugs possessing α-chiral N-functionalities, such as carbamate, carboxylamide, secondary and tertiary amine, and oxazoline, with commonly seen α-substitution patterns. These results shine light on the potential of enantioconvergent radical cross-coupling as a general chiral carbon-heteroatom formation strategy.
- Cheng, Jiang-Tao,Dong, Xiao-Yang,Gu, Qiang-Shuai,Li, Zhong-Liang,Liu, Juan,Liu, Xin-Yuan,Luan, Cheng,Wang, Fu-Li,Wang, Li-Lei,Yang, Ning-Yuan,Zhang, Yu-Feng
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supporting information
p. 15413 - 15419
(2021/09/30)
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- Giant Optical Activity and Second Harmonic Generation in 2D Hybrid Copper Halides
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Hybrid organic–inorganic metal halides have emerged as highly promising materials for a wide range of applications in optoelectronics. Incorporating chiral organic molecules into metal halides enables the extension of their unique optical and electronic properties to chiral optics. By using chiral (R)- or (S)-methylbenzylamine (R-/S-MBA) as the organic component, we synthesized chiral hybrid copper halides, (R-/S-MBA)2CuCl4, and investigated their optical activity. Thin films of this material showed a record anisotropic g-factor as high as approximately 0.06. We discuss the origin of the giant optical activity observed in (R-/S-MBA)2CuCl4 by theoretical modeling based on density functional theory (DFT) and demonstrate highly efficient second harmonic generation (SHG) in these samples. Our study provides insight into the design of chiral materials by structural engineering, creating a new platform for chiral and nonlinear photonic device applications of the chiral hybrid copper halides.
- Guo, Zhihang,Li, Junzi,Wang, Changshun,Liu, Rulin,Liang, Jiechun,Gao, Yang,Cheng, Jiaji,Zhang, Wenjing,Zhu, Xi,Pan, Ruikun,He, Tingchao
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supporting information
p. 8441 - 8445
(2021/03/06)
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- Highly Efficient Spin-Filtering Transport in Chiral Hybrid Copper Halides
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Chiral Pb(Sn)-I hybrid organic–inorganic perovskites exhibit outstanding chiral-induced spin selectivity (CISS) performance, but the nontoxic lead-free hybrid materials with high stability are still greatly desired for spin filtering in spintronic applica
- Cao, Hui,He, Ruilin,He, Wanli,Lu, Ying,Pan, Feng,Song, Cheng,Wang, Dong,Wang, Qian,Yang, Xia,Yang, Zhou,Zhou, Foxin
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supporting information
p. 23578 - 23583
(2021/10/04)
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- Chiral Bronsted Acids Catalyze Asymmetric Additions to Substrates that Are Already Protonated: Highly Enantioselective Disulfonimide-Catalyzed Hantzsch Ester Reductions of NH-Imine Hydrochloride Salts
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While imines are frequently used substrates in asymmetric Bronsted acid catalysis, their corresponding salts are generally considered unsuitable reaction partners. Such processes are challenging because they require the successful competition of a catalytic amount of a chiral anion with a stoichiometric amount of an achiral one. We now show that enantiopure disulfonimides enable the asymmetric reduction of N-H imine hydrochloride salts using Hantzsch esters as hydrogen source. Our scalable reaction delivers crystalline primary amine salts in great efficiency and enantioselectivity and the discovery suggests potential of this approach in other Bronsted acid catalyzed transformations of achiral iminium salts. Kinetic studies and acidity data suggest a bifunctional catalytic activation mode.
- Wakchaure, Vijay N.,Obradors, Carla,List, Benjamin
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supporting information
p. 1707 - 1712
(2020/08/28)
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- Development of an in situ-Product Crystallization (ISPC)-Concept to Shift the Reaction Equilibria of Selected Amine Transaminase-Catalyzed Reactions
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The synthesis of enantiopure amines via amine transaminases involves several challenges including unfavorable reaction equilibria and product inhibition. Described here is a non-catalytic approach to overcome such problems by using an in situ-product crystallization (ISPC) to selectively remove a targeted product amine from an amine transaminase-catalyzed reaction. The continuous removal of the product amine from its reaction solution as a barely soluble salt effectively yields a displacement of the reaction equilibrium towards the products and facilitates a simple downstream processing approach via filtration. The targeted product amine is eventually obtained from the salt, while the counterion compound can be easily recycled.
- Hülsewede, Dennis,T?nzler, Marco,Süss, Philipp,Mildner, Andrea,Menyes, Ulf,von Langermann, Jan
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p. 2130 - 2133
(2018/05/31)
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- A split preparation of the optically pure S-1-benzoethylamine method
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The present invention relates to a method for resolution preparation of S-1-phenylethylamine in a dynamic kinetics manner. According to the method, 1-phenylethylamine is adopted as a raw material, Novozym435 is adopted as a resolution catalyst, S-1-phenethyl acetate is adopted as an acyl donor, raney nickel is adopted as a racemic catalyst, and hydrogen is introduced into an autoclave to carry out a reaction, wherein the 1-phenylethylamine is completely converted to obtain (S)-(1-phenylethyl)acetamide (ee value of 99%), the amide is purified and then acidolysis is performed to obtain a S-1-phenylethylamine salt, and the salt is subjected to alkalization, extraction, drying, concentration and other operations to obtain the S-1-phenylethylamine, wherein the product yield in each step can achieve more than 90%, and the ee values are more than 99%. The method of the present invention has characteristics of cheap and easily-available racemic catalyst, complete raw material use, good product yield, high optical purity and the like. In addition, great guidance and application values are provided in the S-1-phenylethylamine production preparation.
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- One-pot asymmetric reductive amination of ketones induced by polyfluoroalkanesulfinamide
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Using chiral 2-chloro-1,1,2,2-tetrafluoroethane-1-sulfinamide as the auxiliary, an efficient one-pot procedure for the asymmetric reductive amination of ketones was achieved in the presence of sodium borohydride. Both aromatic and aliphatic ketones reacte
- Yang, Kai,Liu, Jin-Tao
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- Rhodium-catalyzed asymmetric hydrogenation of unprotected NH imines assisted by a thiourea
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Asymmetric hydrogenation of unprotected NH imines catalyzed by rhodium/bis(phosphine)-thiourea provided chiral amines with up to 97% yield and 95% ee. 1HNMR studies, coupled with control experiments, implied that catalytic chloride-bound intermediates were involved in the mechanism through a dual hydrogen-bonding interaction. Deuteration experiments proved that the hydrogenation proceeded through a pathway consistent with an imine.
- Zhao, Qingyang,Wen, Jialin,Tan, Renchang,Huang, Kexuan,Metola, Pedro,Wang, Rui,Anslyn, Eric V.,Zhang, Xumu
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supporting information
p. 8467 - 8470
(2014/08/18)
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- STEREOSELECTIVE SYNTHESIS OF METYROSINE
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Provided herein are compositions including diastereomers in substantially diastereomerically pure form and enantiomers in substantially enantiomerically pure form, and processes for preparing them and converting them to metyrosine.
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Page/Page column 15
(2011/05/08)
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- Synthesis and extraction properties of some lariat ethers derived from the spontaneously resolved guaifenesin, 3-(2-methoxyphenoxy)propane-1,2-diol
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Capable of spontaneous resolution rac-3-(2-methoxyphenoxy)propane-1,2-diol, guaifenesin 1 has been proposed as a cheap and readily available enantiopure precursor for the synthesis of nonracemic crown ethers having ligating OAr and OMe arms (lariat ethers). The crowns studied failed to form stable host/guest complexes with amine hydrochloride salts; the effective complexation was achieved using hexafluorophosphate salts. Moderate enantiomeric recognition of R*NH2·HPF6 was achieved with the lariat ethers 11c. As a whole, the enantioselectivity of the extraction is inversely related to the extractive power of the lariat ether. ARKAT-USA, Inc.
- Bredikhina, Zemfira A.,Eliseenkova, Rimma M.,Fayzullin, Robert R.,Novikova, Viktorina G.,Kharlamov, Sergey V.,Sharafutdinova, Dilyara R.,Latypov, Shamil K.,Bredikhin, Alexander A.
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experimental part
p. 16 - 32
(2011/09/21)
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- Metal-organic frameworks with designed chiral recognition sites
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Linking struts containing Cram-like bisbinaphthyl[22]crown-6 with Zn 4O(CO2)6 joints affords metal-organic frameworks with chiral recognition sites that are highly designed, ordered and placed in a precise manner throughou
- Valente, Cory,Choi, Eunwoo,Belowich, Matthew E.,Doonan, Christian J.,Li, Qiaowei,Gasa, Travis B.,Botros, Youssry Y.,Yaghi, Omar M.,Stoddart, J. Fraser
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supporting information; experimental part
p. 4911 - 4913
(2010/08/07)
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- Recycling the tert-butanesulfinyl group in the synthesis of amines using tert-butanesulfinamide
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A practical process for recycling the tert-butanesulfinyl group upon deprotection of N-tert-butanesulfinyl amines has been achieved. Treatment of N-tert-butanesulfinyl amines with HCl in cyclopentyl methyl ether results in complete conversion to tert-butanesulfinyl chloride and the corresponding amine hydrochloride salt, which is isolated by filtration in analytically pure form and in quantitative yield. Treatment of the resulting sulfinyl chloride solution with aqueous ammonia then provides analytically pure tert-butanesulfinamide in 97% yield. Alternatively, the tert-butanesulfinyl chloride solution can be treated with ethanol and catalytic quinidine as a sulfinyl transfer catalyst to provide a cyclopentyl methyl ether solution of ethyl tert-butanesulfinate with 88% ee. Addition of NaNH2 in ammonia followed by simple trituration of the product with octane provides tert-butanesulfinamide with 99% ee and in 67% overall isolated yield based upon the starting N-tert-butanesulfinyl amine.
- Wakayama, Masakazu,Ellman, Jonathan A.
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experimental part
p. 2646 - 2650
(2009/08/15)
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- Selective diethylzinc reduction of imines in the presence of ketones catalyzed by Ni(acac)2
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(Chemical Equation Presented) A selective reduction method of an electronically deficient imine in the presence of ketone was developed by employing Et2Zn and 5 mol % of Ni(acac)2. The method was applied in the reduction of SS-tert-butanesulfinyl ketimines 1 to afford amines 2 in 23-92% yields and 73:27 to 98:2 diastereoselectivities. A plausible mechanism was proposed on the basis of an NMR study.
- Xiao, Xue,Wang, Haowei,Huang, Zhiyan,Yang, Jun,Bian, Xiaoxia,Qin, Yong
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p. 139 - 142
(2007/10/03)
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- Reversal of diastereofacial selectivity in hydride reductions of N-tert-butanesulfinyl imines
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A variety of N-tert-butanesulfinyl imines were reduced with NaBH 4 in THF containing 2% water to provide the corresponding secondary sulfinamides in high yield and diastereoselectivity. By using the same sulfinyl imine starting materials and changing the reductant to L-Selectride, the stereoselectivity could be efficiently reversed to afford the opposite product diastereomer in high yield and selectivity.
- Colyer, John T.,Andersen, Neil G.,Tedrow, Jason S.,Soukup, Troy S.,Faul, Margaret M.
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p. 6859 - 6862
(2007/10/03)
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- Enantioselective nucleophilic addition to N-(2-pyridylsulfonyl)imines by use of dynamically induced chirality
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Enantioselective nucleophilic addition of Grignard reagents to N-(2-pyridylsulfonyl)imines in the presence of bis(oxazoline) afforded products with good enantioselectivity. Dynamically induced chiralitxy on the sulfur by coordination of a chiral Lewis aci
- Sugimoto, Hideki,Nakamura, Shuichi,Hattori, Masataka,Ozeki, Sachiko,Shibata, Norio,Toru, Takeshi
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p. 8941 - 8944
(2007/10/03)
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- Multicomponent one-pot procedure for the synthesis of free α-chiral amines from aldehydes
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The synthesis of free a-chiral amines by a one-pot multi-component procedure from commercially available starting materials is described. This enantioselective reaction involves a catalytic asymmetric addition of dialkylzinc reagents to N-diphenylphosphin
- Cote, Alexandre,Charette, Andre B.
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p. 10864 - 10867
(2007/10/03)
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- Orthoacylimines: A new class of chiral auxiliaries for nucleophilic addition of organolithium reagents to imines
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A new class of orthoacylimine-derived chiral auxiliaries has been synthesized and tested in the nucleophilic addition of organolithium reagents to imines. The precursors can be prepared by an aza-Wittig reaction between the corresponding orthoacyl azide and a variety of aldehydes in the presence of trialkylphosphines. The nucleophilic addition of organolithium reagents led to the addition products in good yields and with good to excellent diastereoselectivities (from 85:15 to 99:1). The chiral, nonracemic secondary amines could be readily obtained under mild hydrolytic condition. Furthermore, the chiral auxiliary can be recovered in quantitative yield and reconverted to the starting orthoacyl azide precursor. This method was applied to the synthesis of (S)-t-leucine.
- Boezio, Alessandro A.,Solberghe, Geoffrey,Lauzon, Caroline,Charette, Andre B.
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p. 3241 - 3245
(2007/10/03)
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- Resolution of chiral aliphatic and arylalkyl amines using immobilized Candida antarctica lipase and isolation of their R- and S-enantiomers
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The resolution of chiral aliphatic and arylalkyl amines in high enantiomeric excess (up to 97.5% ee for the R-enantiomers and up to 99.9% ee for the S-enantiomers) and good yield (50-80%) using immobilized Candida antarctica lipase and ethyl acetate as acyl donor has been demonstrated. A second resolution on the Ramine increased the enantiomeric excess to more than 99.5% (up to 99.9%).
- Davis,Durden
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p. 569 - 578
(2007/10/03)
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- Asymmetric synthesis of chiral amines by highly diastereoselective 1,2- additions of organometallic reagents to N-tert-butanesulfinyl imines
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High yielding and highly diastereoselective methods for 1,2-additions of organometallic reagents to N-tert-butanesulfinyl aldimines (2) and N-tert- butanesulfinyl kerimines (3) are described. The additions of alkyl, aryl, alkenyl, and allyl carbanions to a diverse set of imines with different steric and electronic properties are demonstrated. Acidic methanolysis of the sulfinamide products (4 and 6) delivers highly enantioenriched α-branched and α,α-dibranched amines. Since a broad range of sulfinyl imines are easily accessible from aldehydes and ketones, a wide variety of enantioentriched amines may be prepared.
- Cogan, Derek A.,Liu, Guangcheng,Ellman, Jonathan
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p. 8883 - 8904
(2007/10/03)
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- Chiral Synthesis via Organoboranes. 30. Facile Synthesis, by the Matteson Asymmetric Homologation Procedure, of α-Methyl Boronic Acids Not Available from Asymmetric Hydroboration and Their Conversion into the Corresponding Aldehydes, Ketones, Carboxylic Acids, and Amines of High Enan...
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2-(α-Methylalkyl)- or 2-(α-arylethyl)-1,3,2-dioxaborinanes, RMeHC*BO2(CH2)3 (R = alkyl or aryl), of very high enantiomeric purity, not available from asymmetric hydroboration, can be prepared by the Matteson asymmetric homologation procedure of optically pure pinanediol or 2,3-butanediol boronate esters with (dichloromethyl)lithium, LiCHCl2, conveniently generated in situ in THF at -78 deg C, followed by reaction with either a Grignard reagent or an alkyllithium, with subsequent removal of the chiral auxiliaries. α-Methyl boronic esters thus obtained are readily converted into the corresponding aldehydes by the reaction with lithium (MPML) and mercuric chloride, followed by oxidation with hydrogen peroxide in a pH 8 buffer medium.The two-phase aqueous chromic acid procedure can be used to oxidize these aldehydes to the corresponding α-methyl carboxylic acids of very high enantiomeric purity without significant racemization.Additionally, pinanediol or 2,3-butanediol α-methylorganylboronate esters can be conveniently converted into borinic ester derivatives, RMeHC*BMe(OMe), of very high enantiomeric purity by reaction with methyllithium, followed by treatment with methanolic hydrogen chloride and subsequent recovery of the valuable chiral auxiliaries.These borinic ester derivatives are converted into α-methyl ketones and α-methyl primary amines of known absolute configuration by the α,α-dichloromethyl methyl ether (DCME) reaction and the reaction with hydroxylamine-O-sulfonic acid, respectively.The present synthesis of chiral 2-organyl-1,3,2-dioxaborinanes by the Matteson route, together with our direct asymmetric hydroboration procedure, makes it possible to synthesize many chiral boronic acid derivatives in very high enantiomeric purities.These complementary procedures greatly expand the scope of asymmetric synthesis via chiral organoboranes.
- Rangaishenvi, Milind V.,Singaram, Bakthan,Brown, Herbert C.
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p. 3286 - 3294
(2007/10/02)
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- Preparation of the diastereomeric mixture 2R,4S-1-[2-(2,4-dichlorophenyl)-4-n-propyl-1,3-dioxolan-2-ylmethyl]-1H-1,2,4-triazole
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The 2R,4S-isomer of formula I and the 2RS,4S-diastereoisomeric mixture of formula Ia of 1-[2-(2,4-dichlorophenyl)-4-n-propyl-1,3-dioxolan-2-ylmethyl]-1H-1,2,4-triazole STR1 and the preparation thereof are described. The compounds of formulae I and Ia have pronounced microbicidal activity without having phytotoxic side-effects. They are used as active ingredients in microbicidal compositions, especially as seed dressings.
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