756875-61-3Relevant academic research and scientific papers
Enantiodivergent α-Amino C-H Fluoroalkylation Catalyzed by Engineered Cytochrome P450s
Zhang, Juner,Huang, Xiongyi,Zhang, Ruijie K.,Arnold, Frances H.
supporting information, p. 9798 - 9802 (2019/07/04)
The introduction of fluoroalkyl groups into organic compounds can significantly alter pharmacological characteristics. One enabling but underexplored approach for the installation of fluoroalkyl groups is selective C(sp3)-H functionalization due to the ubiquity of C-H bonds in organic molecules. We have engineered heme enzymes that can insert fluoroalkyl carbene intermediates into α-amino C(sp3)-H bonds and enable enantiodivergent synthesis of fluoroalkyl-containing molecules. Using directed evolution, we engineered cytochrome P450 enzymes to catalyze this abiological reaction under mild conditions with total turnovers (TTN) up to 4070 and enantiomeric excess (ee) up to 99%. The iron-heme catalyst is fully genetically encoded and configurable by directed evolution so that just a few mutations to the enzyme completely inverted product enantioselectivity. These catalysts provide a powerful method for synthesis of chiral organofluorine molecules that is currently not possible with small-molecule catalysts.
Aerobic intramolecular aminothiocyanation of unactivated alkenes promoted by in situ generated iodine thiocyanate
Feng, Yangyang,Hussain, Muhammad Ijaz,Zhang, Xiaohui,Shi, Jian,Hu, Wen,Xiong, Yan
supporting information, p. 2669 - 2676 (2018/05/04)
Aerobic intramolecular aminothiocyanation of unactivated alkenes has been developed by in situ generated iodine thiocyanate under open-flask conditions. This protocol provides a concise and efficient method for synthesizing SCN-containing pyrrolidine, piperidine and indoline derivatives with isolated yields of up to 87%. Furthermore, mixing iodine and sodium thiocyanate with oxygen afforded iodine thiocyanate (ISCN) and dithiocyanatoiodate [I(SCN)2]- which were testified by liquid chromatography mass spectrometry. A mechanistic investigation indicates that iodonium ion and sulfonium ion intermediates might be involved in this transformation.
Use of (cyclopentadienone)iron tricarbonyl complexes for c-n bond formation reactions between amines and alcohols
Brown, Thomas J.,Cumbes, Madeleine,Diorazio, Louis J.,Clarkson, Guy J.,Wills, Martin
, p. 10489 - 10503 (2018/05/31)
The application of a series of (cyclopentadienone)iron tricarbonyl complexes to "borrowing hydrogen" reactions between amines and alcohols was completed in order to assess their catalytic activity. The electronic variation of the aromatic groups flanking the C?O of the cyclopentadienone influenced the efficiency of the reactions; however, in other cases, the Kn?lker catalyst 1, containing trimethylsilyl groups flanking the cyclopentadienone ketone, gave the best results. In some cases, the change of the ratio of amine to alcohol improves the conversion significantly. The application of iron catalysts to the synthesis of a range of amines, including unsaturated amines, was investigated.
Pd(0)-catalyzed alkene oxy- and aminoalkynylation with aliphatic bromoacetylenes
Nicolai, Stefano,Sedigh-Zadeh, Raha,Waser, Jeroime
, p. 3783 - 3801 (2013/06/26)
Tetrahydrofurans and pyrrolidines are among the most important heterocycles found in bioactive compounds. Cyclization-functionalization domino reactions of alcohols or amines onto olefins constitute one of the most efficient methods to access them. In this context, oxy- and aminoalkynylation are especially important reactions, because of the numerous transformations possible with the triple bond of acetylenes, yet these methods have been limited to the use of silyl protected acetylenes. Herein, we report the first palladium-catalyzed oxy- and aminoalkynylation using aliphatic bromoalkynes, which proceeded with high diastereoselectivity and functional group tolerance. A one-pot hydrogenation of the triple bond gave then access to alkyl-substituted tetrahydrofurans and pyrroldines. Finally, a detailed study of the side products formed during the reaction gave a first insight into the reaction mechanism.
FeCl2-promoted cleavage of the unactivated C-C bond of alkylarenes and polystyrene: Direct synthesis of arylamines
Qin, Chong,Shen, Tao,Tang, Conghui,Jiao, Ning
, p. 6971 - 6975 (2012/09/25)
Ironing it out: An efficient and convenient nitrogenation strategy involving C-C bond cleavage for the straightforward synthesis of versatile arylamines is presented. Various alkyl azides and alkylarenes, including the common industrial by-product cumene, react using this protocol. Moreover, this method provides a potential strategy for the degradation of polystyrene. Copyright
Palladium-catalyzed synthesis of N-aryl pyrrolidines from γ-(N-arylamino) alkenes: Evidence for chemoselective alkene insertion into Pd-N bonds
Ney, Joshua E.,Wolfe, John P.
, p. 3605 - 3608 (2007/10/03)
The formation of a C-C and a C-N bond in a reaction between γ-(N-arylamino) alkenes and aryl bromides results in the stereoselective synthesis of substituted pyrrolidine derivatives (see scheme). Preliminary studies suggest these reactions proceed by intramolecular alkene insertion into the Pd-N bond of intermediate [Pd(Ar)(amido)] complexes. dba = dibenzylideneacetone, dppb = 1,3-bis(diphenylphosphanyl) butane.
Dirhodium Tetraacetate Catalyzed Carbon-Hydrogen Insertion Reaction in N-Substituted α-Carbomethoxy-α-diazoacetanilides and Structural Analogues. Substituent and Conformational Effects
Wee, Andrew G. H.,Liu, Baosheng,Zhang, Lin
, p. 4404 - 4414 (2007/10/02)
A series of acyclic α-carbomethoxy-α-diazoacetanilides with different N-substituents, 5a-k, was prepared and the rhodium(II) acetate catalyzed reaction studied.It was found that the rhodium carbenoid reaction with these compounds occurred only at the N-substituent; when the N-substituent is a propargyl group, rhodium carbenoid addition to the triple bond is favored, resulting, ultimately, in the formation of a bicyclic furan derivative 8.With an N-(tert-butyloxycarbonyl)methyl substituent, interception of the rhodium carbenoid by the ester carbonyl oxygen occurred preferentially to give, eventually, 1,4-oxazine derivatives 9 and 9'.For N'-alkyl substituents, rhodium carbenoid carbon-hydrogen (C-H) insertion into the alkyl group to give the 2-azetidinone and/or 2-pyrrolidinone derivatives was observed.The chemoselectivity of the rhodium carbenoid C-H insertion can be altered by the use of the α-acetyl and α-phenylsulfonyl substituents.In these cases, exclusive C-H insertion at the N-aryl moiety resulted to give 2(3H)-indolinone products.However, the α-substituent effect on the chemoselectivity of the insertion reaction is easily overridden by conformational effects about the amide N-C(O) bond as revealed by the insertion reaction of the conformationally rigid compounds 20a-c.The α-substituent effects are reestablished when conformational rigidity is removed, as exemplified by the rhodium carbenoid insertion reactions of compounds 29a, b.
