81097-36-1Relevant academic research and scientific papers
Exploring Electrochemical C(sp3)-H Oxidation for the Late-Stage Methylation of Complex Molecules
Ho, Justin S. K.,Lin, Song,Liu, Kaida,Mao, Kaining,Neurock, Matthew,Novaes, Luiz F. T.,Tanwar, Mayank,Terrett, Jack A.,Villemure, Elisia
supporting information, p. 1187 - 1197 (2022/02/05)
The magic methyl effect, a dramatic boost in the potency of biologically active compounds from the incorporation of a single methyl group, provides a simple yet powerful strategy employed by medicinal chemists in the drug discovery process. Despite significant advances, methodologies that enable the selective C(sp3)-H methylation of structurally complex medicinal agents remain very limited. In this work, we disclose a modular, efficient, and selective strategy for the α-methylation of protected amines (i.e., amides, carbamates, and sulfonamides) by means of electrochemical oxidation. Mechanistic analysis guided our development of an improved electrochemical protocol on the basis of the classic Shono oxidation reaction, which features broad reaction scope, high functional group compatibility, and operational simplicity. Importantly, this reaction system is amenable to the late-stage functionalization of complex targets containing basic nitrogen groups that are prevalent in medicinally active agents. When combined with organozinc-mediated C-C bond formation, our protocol enabled the direct methylation of a myriad of amine derivatives including those that have previously been explored for the magic methyl effect. This synthesis strategy thus circumvents multistep de novo synthesis that is currently necessary to access such compounds and has the potential to accelerate drug discovery efforts.
Nickel-Catalyzed Cyanation of Unactivated Alkyl Sulfonates with Zn(CN)2
Xia, Aiyou,Lv, Peizhuo,Xie, Xin,Liu, Yuanhong
, p. 7842 - 7847 (2020/11/02)
Cyanation of unactivated primary and secondary alkyl mesylates with Zn(CN)2 catalyzed by nickel has been developed. The reaction provides an efficient route for the synthesis of alkyl nitriles with wide substrate scope, good functional group tolerance, and compatibility with heterocyclic compounds. Mechanistic studies indicate that alkyl iodide generated in situ serves as the reactive intermediate and the gradual release of alkyl iodide is crucial for the success of the reaction.
Synthesis and Structural Elucidation of 1,2-Disubstituted 3-Fluoropiperidines
Evans, Paul,Fischer, Pauline,Müller-Bunz, Helge,Morris, Morgan
, (2020/02/28)
The work described details the reaction between Selectfluor and a series of 1-carbonyloxy and 1-sulfonyl 2-piperidines in order to generate 3-fluoro-2-methoxypiperidines 3a–f. Their subsequent reaction with allyltrimethylsilane, in the presence of BF3 and TiCl4, is then reported. Studies involving a combination of single-crystal X-ray crystallography and NMR spectroscopy indicate that the allylation process is cis-selective for both carbamate and sulfonamide variants and that optimal levels of diastereoselectivity are obtained using the N-2-nitrobenzene sulfonyl (2-Ns) group. In this manner, the synthesis of a series of 2-allyl 3-fluoro-substituted piperidines (5a, c–f) was achieved. The conversion of both the cis and trans-N-tosyl adducts (5d) into 3-fluorinated analogues of the natural products pelletierine (10) and coniine (11) is subsequently detailed.
Pentannulation of N-heterocycles by a tandem gold-catalyzed [3,3]-rearrangement/Nazarov reaction of propargyl ester derivatives: A computational study on the crucial role of the nitrogen atom
Zanella, Giovanna,Petrovi?, Martina,Scarpi, Dina,Occhiato, Ernesto G.,Gómez-Bengoa, Enrique
, p. 3059 - 3068 (2021/01/15)
The tandem gold(I)-catalyzed rearrangement/Nazarov reaction of enynyl acetates in which the double bond is embedded in a piperidine ring was computationally and experimentally studied. The theoretical calculations predict that the position of the propargy
Rh-catalyzed intramolecular cyclization of 1-sulfonyl-1,2,3-triazole and sulfinate. Concise preparation of sulfonylated unsaturated piperidines
Furukawa, Ayana,Hata, Takeshi,Shigeta, Masayuki,Urabe, Hirokazu
, p. 815 - 819 (2019/02/25)
When 4-[3-(methanesulfinyloxy)propyl]-1-(arenesulfonyl)-1,2,3-triazoles were treated with rhodium catalysts of the type Rh2(RCO2)4, a new intramolecular cyclization took place to afford 2,3-didehydro-1-(arenesulfonyl)-3-(m
Preparation method of spiro-2-azidoindoline
-
Paragraph 0048; 0049; 0050; 0051, (2016/10/10)
The invention provides a preparation method of a compound represented by the formula (III) or formula (IV). According to the preparation method, in an inert atmosphere, indoles represented by the formula (I) or (II), a precursor that can provide azido groups, and ceric ammonium nitrate carry out reactions to obtain the spiro-2-azidoindoline. In the formula (I), (II), (III), and (IV), the R1 represents at least one of hydrogen, a C1-C5 alkyl group, a C1-C5 alkyloxy group, F, Br and Cl; the X represents O or TsN, TsN represents p-toluenesulfonyl; and the R2 represents a C1-C5 alkyl group. The precursor is sodium azide or trimethylsilyl azide. The mole ratio of indoles represented by the formula (I) or (II) to precursor to ceric ammonium nitrate is 1:(1-3):(2-6). According to the preparation method, azide is introduced into an organic molecule through a simple method, namely, indoles with different structures are tank as the raw materials, and under the effects of a precursor that can provide azido groups and ceric ammonium nitrate, spiro-2-azidoindoline is successfully prepared. The provided method has the advantages of easily prepared raw materials, mild reaction conditions, and convenient operation, and the yield can reach 94%.
Laccase/2,2,6,6-tetramethylpiperidinoxyl radical (TEMPO): An efficient catalytic system for selective oxidations of primary hydroxy and amino groups in aqueous and biphasic media
Díaz-Rodríguez, Alba,Martínez-Montero, Lía,Lavandera, Iván,Gotor, Vicente,Gotor-Fernández, Vicente
, p. 2321 - 2329 (2014/07/21)
Copper salts/2,2,6,6-tetramethylpiperidinoxyl radical (TEMPO) catalytic systems enable efficient aerobic oxidations of primary alcohols but they generally show a reduced reactivity in aqueous medium. Herein, we report an oxidative catalytic system composed of Trametes versicolor laccase and TEMPO, which is able to work in buffer solutions at room temperature using ambient air. Although this catalytic system displays great efficiency in aqueous systems, the addition of methyl tert-butyl ether allows the reduction of TEMPO loading, also enhancing the solubility of hydrophobic compounds. This practical methodology promotes the chemoselective aerobic oxidation of hydroxy or amino groups, leading to interesting organic derivatives such as aldehydes, lactones, hemiaminals or lactams.
A six-coordinated cationic ruthenium carbyne complex with liable pyridine ligands: Synthesis, structure, catalytic investigation, and DFT study on initiation mechanism
Liu, Guiyan,Zheng, Lu,Shao, Mingbo,Zhang, Huizhu,Qiao, Weixia,Wang, Xiaojia,Liu, Bowen,Zhao, Haitao,Wang, Jianhui
supporting information, p. 4718 - 4725 (2014/06/24)
A novel six-coordinated high-valence cationic ruthenium carbyne complex bearing two liable pyridine ligands was prepared in high yield by the reaction of the ruthenium-based complex (IMesH2)(Cl)2(C 5H5N)2RuCHPh [IMesH2=1,3-dimesityl- 4,5-dihydroimida-zol-2-ylidene] with excess iodine as an oxidant in CH 2Cl2 at 25 °C under N2. The new ruthenium carbyne-based complex shows moderate to good catalytic activity for ring-closing metathesis reactions. Importantly, no double bond isomerization by-product was produced at elevated reaction temperatures (100 °C-137 °C) in the reaction catalyzed by the synthesized ruthenium carbyne complex. A mechanism involving the in situ conversion of the ruthenium carbyne through the addition of an iodide to the carbyne carbon was also proposed, and DFT calculations were performed to explain the initiating mechanism.
A unique ruthenium carbyne complex: A highly thermo-endurable catalyst for olefin metathesis
Wang, Jianhui,Shao, Mingbo,Zheng, Lu,Qiao, Weixia,Wang, Jingjing
supporting information, p. 2743 - 2750,8 (2012/12/12)
A cationic ruthenium carbyne complex was prepared and was found to initiate olefin metathesis reactions with good activities, which throws a new light on the design of a new type of ruthenium catalyst for RCM reactions. More importantly, no double bond isomerized by-product was observed even at elevated temperatures in reactions catalyzed by the new carbyne complex. A mechanism involving the in situ conversion of the ruthenium carbyne to a ruthenium carbene complex via addition of an iodide to the carbyne carbon was also proposed.
Synthesis, structure and catalytic study of chloro-bridged two-core ruthenium carbene complexes
Qiao, Weixia,Shao, Mingbo,Wang, Jianhui
experimental part, p. 197 - 202 (2012/08/27)
The reaction of a ruthenium carbide complex RuCl2(C:) (PCy 3)2 with [H(Et2O)x] +[BF4]- at a molar ratio of 1:2 produced a two-core ruthenium carbene complex {[RuCl(CHPCy3)(PCy 3)]2(μ-Cl)3}+·[BF 4]- (8) in the form of a yellow-green crystalline solid. After a ligand exchange reaction of 8 with LiBr, a bromide ruthenium carbene complex {[RuBr(CHPCy3)(PCy3)]2(μ-Cl) 3}+·[BF4]- (9) was obtained as a crystalline solid. Catalytic studies showed that both 8 and 9 are selective catalysts for ring closing metathesis of unsubstituted terminal dienes. More importantly, no isomerized byproduct was observed when 8, or 9 was used as the catalyst at an elevated temperature (137 °C), indicating that both 8 and 9 are chemo-selective catalysts for ring closing metathesis reactions.
