73627-97-1Relevant academic research and scientific papers
Direct Catalytic Asymmetric Addition of Alkylnitriles to Aldehydes with Designed Nickel–Carbene Complexes
Saito, Akira,Adachi, Shinya,Kumagai, Naoya,Shibasaki, Masakatsu
supporting information, p. 8739 - 8743 (2021/03/16)
A direct catalytic asymmetric addition of acetonitrile to aldehydes that realizes over 90 % ee is the ultimate challenge in alkylnitrile addition chemistry. Herein, we report achieving high enantioselectivity by the strategic use of a sterically demanding NiII pincer carbene complex, which afforded highly enantioenriched β-hydroxynitriles. This highly atom-economical process paves the way for exploiting inexpensive acetonitrile as a promising C2 building block in a practical synthetic toolbox for asymmetric catalysis.
Hf-MOF catalyzed Meerwein?Ponndorf?Verley (MPV) reduction reaction: Insight into reaction mechanism
Lin, Yamei,Bu, Qingxia,Xu, Jiaxian,Liu, Xiao,Zhang, Xueping,Lu, Guo-Ping,Zhou, Baojing
, (2021/01/25)
Hf-MOF-808 exhibits excellent activity and specific selectivity on the hydrogenation of carbonyl compounds via a hydrogen transfer strategy. Its superior activity than other Hf-MOFs is attributed to its poor crystallinity, defects and large specific surface area, thereby containing more Lewis acid-base sites which promote this reaction. Density functional theory (DFT) computations are performed to explore the catalytic mechanism. The results indicate that alcohol and ketone fill the defects of Hf-MOF to form a six-membered ring transition state (TS) complex, in which Hf as the center of Lewis stearic acid coordinates with the oxygen of the substrate molecule, thus effectively promoting hydrogen transfer process. Other reactive groups, such as –NO2, C = C, -CN, of inadequate hardness or large steric hindrance are difficult to coordinate with Hf, thus weakening their catalytic effect, which explains the specific selectivity Hf-MOF-808 for reducing the carbonyl group.
Chiral Benzothiophene Synthesis via Enantiospecific Coupling of Benzothiophene S-Oxides with Boronic Esters
Aggarwal, Varinder K.,Noble, Adam,Sang, Ruocheng
supporting information, p. 25313 - 25317 (2021/11/09)
Benzothiophenes are valuable heterocycles that are widely used in medicines, agrochemicals, and materials science. Herein, we report a general method for the synthesis of enantioenriched 2,3-disubstituted benzothiophenes via a transition-metal-free C2-alkylation of benzothiophenes with boronic esters. The reactions utilize benzothiophene S-oxides in lithiation-borylations to generate intermediate arylboronate complexes, and subsequent Tf2O-promoted S?O bond cleavage to trigger a Pummerer-type 1,2-metalate shift, which gives the coupled products with complete enantiospecificity. Primary, secondary and tertiary alkyl boronic esters and aryl boronic esters are successfully coupled with a range of C3-substituted benzothiophenes. Importantly, this transformation does not require the use of C3 directing groups, therefore it overcomes a major limitation of previously developed transition-metal-mediated C2 alkylations of benzothiophenes.
Cellulosic CuI Nanoparticles as a Heterogeneous, Recyclable Catalyst for the Borylation of α,β-Unsaturated Acceptors in Aqueous Media
Zhou, Lijie,Han, Biao,Zhang, Yaoyao,Li, Bojie,Wang, Liansheng,Wang, Jianying,Wang, Xianbao,Zhu, Lei
, p. 3220 - 3229 (2021/03/06)
Abstract: We have demonstrated that cellulosic CuI nanoparticles could perform as an efficient heterogeneous catalyst for the synthesis of useful organoboron compounds. Desired β-borylation products were all obtained in good to excellent yields under mild
Reaction of electrogenerated cyanomethyl anion with cyclohexylisocyanate: Synthesis of N-(cyclohexylcarbamoyl) acetamide. An unexpected product
Bortolami, Martina,Feroci, Marta,Pandolfi, Fabiana,Petrucci, Rita,Rocco, Daniele,Scarano, Vincenzo,Zollo, Giuseppe
, (2020/10/21)
The contamination with water of the cathodic ACN-Et4NBF4 solution gave us the opportunity to investigate alkyl isocyanate reactivity toward electrogenerated anions. The cathodic reduction of a ACN-Et4NBF4 solution led to the formation of both hydroxide and cyanomethyl anions. The reaction of the catholyte with cyclohexylisocyanate led to the exclusive formation of acetamidated product, with no traces of cyanomethylated one. On the contrary, when reacting with benzaldehyde only the cyanomethylated was isolated. Considering that the acetamidated product of benzaldehyde is reported to be unstable (thus its formation cannot be excluded), various experiments were carried out in order to understand the anomalous reactivity of cyclohexylisocyanate. Moreover, computational analysis allowed to state the higher stability of acetamidated product with respect to the cyanomethylated one. The possibility of a concerted reaction, instead of acetamide anion formation prior to the reaction, is still an open question.
Biocatalytic asymmetric ring-opening of dihydroisoxazoles: a cyanide-free route to complementary enantiomers of β-hydroxy nitriles from olefins
Asano, Yasuhisa,Zheng, Daijun
supporting information, p. 4930 - 4936 (2020/08/25)
By combination of the cyanide-free synthesis of chiral nitriles and the Kemp elimination reaction catalyzed by aldoxime dehydratases, we herein report a new application of aldoxime dehydratase in the asymmetric ring-opening of 5-sub-4,5-dihydroisoxazoles
Biphasic Bioelectrocatalytic Synthesis of Chiral β-Hydroxy Nitriles
Dong, Fangyuan,Chen, Hui,Malapit, Christian A.,Prater, Matthew B.,Li, Min,Yuan, Mengwei,Lim, Koun,Minteer, Shelley D.
supporting information, p. 8374 - 8382 (2020/05/22)
Two obstacles limit the application of oxidoreductase-based asymmetric synthesis. One is the consumption of high stoichiometric amounts of reduced cofactor. The other is the low solubility of organic substrates, intermediates, and products in the aqueous phase. In order to address these two obstacles to oxidoreductase-based asymmetric synthesis, a biphasic bioelectrocatalytic system was constructed and applied. In this study, the preparation of chiral β-hydroxy nitriles catalyzed by alcohol dehydrogenase (AdhS) and halohydrin dehalogenase (HHDH) was investigated as a model bioelectrosynthesis, since they are high-value intermediates in statin synthesis. Diaphorase (DH) was immobilized by a cobaltocene-modified poly(allylamine) redox polymer on the electrode surface (DH/Cc-PAA bioelectrode) to achieve effective bioelectrocatalytic NADH regeneration. Since AdhS is a NAD-dependent dehydrogenase, the diaphorase-modified biocathode was used to regenerate NADH to support the conversion from ethyl 4-chloroacetoacetate (COBE) to ethyl (S)-4-chloro-3-hydroxybutanoate ((S)-CHBE) catalyzed by AdhS. The addition of methyl tert-butyl ether (MTBE) as an organic phase not only increased the uploading of COBE but also prevented the spontaneous hydrolysis of COBE, extended the lifetime of DH/Cc-PAA bioelectrode, and increased the Faradaic efficiency and the concentration of generated (R)-ethyl-4-cyano-3-hydroxybutyrate ((R)-CHCN). After 10 h of reaction, the highest concentration of (R)-CHCN in the biphasic bioelectrocatalytic system was 25.5 mM with 81.2% enantiomeric excess (eep). The conversion ratio of COBE achieved 85%, which was 8.8 times higher than that achieved with the single-phase system. Besides COBE, two other substrates with aromatic ring structures were also used in this biphasic bioelectrocatalytic system to prepare the corresponding chiral β-hydroxy nitriles. The results indicate that the biphasic bioelectrocatalytic system has the potential to produce a variety of β-hydroxy nitriles with different structures.
A Ball-Milling-Enabled Reformatsky Reaction
Cao, Qun,Stark, Roderick T.,Fallis, Ian A.,Browne, Duncan L.
, p. 2554 - 2557 (2019/06/17)
An operationally simple one-jar one-step mechanochemical Reformatsky reaction using in situ generated organozinc intermediates under neat grinding conditions has been developed. Notable features of this reaction protocol are that it requires no solvent, no inert gases, and no pre-activation of the bulk zinc source. The developed process is demonstrated to have good substrate scope (39–82 % yield) and is effective irrespective of the initial morphology of the zinc source.
Tuning Isonitrile/Tetrazine Chemistry for Accelerated Deprotection and Formation of Stable Conjugates
Xu, Minghao,Deb, Titas,Tu, Julian,Franzini, Raphael M.
, p. 15520 - 15529 (2019/11/29)
The isocyano group is a valuable functionality for bioorthogonal reactions because it rapidly reacts with tetrazines to either form stable conjugates or release payloads from 3-isocyanopropyl groups. Here we provide mechanistic insights into the dissociative steps that follow the initial cycloaddition and analyze how structural modifications affect these processes. Three main outcomes of this study have important implications for designing such groups for bioorthogonal applications. First, anion-stabilizing substituents at C-2 of the 3-isocyanopropyl group promote β-elimination and accelerate deprotection. Second, tetrazines with bulky substituents form stable imine conjugates even with primary isonitriles that are otherwise rapidly hydrolyzed. Third, the elimination step is independent from hydrolysis to the aldehyde and instead can occur directly from the imine intermediate. These findings will allow tuning the structures of tetrazine and isonitrile reactants for application in bioorthogonal ligation and release chemistry.
RAPIDLY RELEASED BIOORTHOGONAL CAGING GROUPS
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Page/Page column 35, (2019/12/25)
Bioorthogonal molecules are disclosed and described. A bioorthogonal a molecule having a structure according to: Formula (I); where R2, R3, and R4 are independently selected from H, a substituted or unsubstituted C1/
