173546-21-9Relevant academic research and scientific papers
Silver Mediated Banert Cascade with Carbon Nucleophiles
Alexander, Juliana R.,Kevorkian, Paul V.,Topczewski, Joseph J.
supporting information, p. 3227 - 3230 (2021/05/05)
The Banert cascade of propargylic azides can be promoted by simple silver salts, and the triazafulvene intermediate can be intercepted by carbon nucleophiles. Various indoles (>25 examples, up to 92% yield) and electron-rich heterocycles were effective. T
Copper-Free Solid-Phase Synthesis of Triazolo[1,5-a][1,4]diazepin-6-ones
Kriegelsteinová, Patricia,Lemrová, Barbora,Ru?ilová, Veronika,Soural, Miroslav
, p. 1112 - 1119 (2021/01/04)
Synthesis of triazolo[1,5-a][1,4]diazepin-6-ones on solid support is reported in this article. Amino acids immobilized on Wang resin were nosylated and alkylated with propargyl alcohol, but-2-yn-1-ol or different 3-phenylprop-2-yn-1-ols using Mitsunobu alkylation conditions. After denosylation, acylation with Fmoc-azidoalanine yielded linear precursors that were thermally cyclized on resin to give immobilized triazolodiazepinones. After cleavage from the polymer support, the target compounds were obtained in high crude purities and good overall yields. Furthermore, the synthetic approach was applied to convenient solid-phase synthesis of oligopeptide containing the triazolodiazepinone moiety as the peptidomimetic heterocyclic constraint. (Figure presented.).
Unified Approach to Furan Natural Products via Phosphine-Palladium Catalysis
Chen, Violet Yijang,Kwon, Ohyun
supporting information, p. 8874 - 8881 (2021/03/17)
Polyalkyl furans are widespread in nature, often performing important biological roles. Despite a plethora of methods for the synthesis of tetrasubstituted furans, the construction of tetraalkyl furans remains non-trivial. The prevalence of alkyl groups in bioactive furan natural products, combined with the desirable bioactivities of tetraalkyl furans, calls for a general synthetic protocol for polyalkyl furans. This paper describes a Michael–Heck approach, using sequential phosphine-palladium catalysis, for the preparation of various polyalkyl furans from readily available precursors. The versatility of this method is illustrated by the total syntheses of nine distinct polyalkylated furan natural products belonging to different classes, namely the furanoterpenes rosefuran, sesquirosefuran, and mikanifuran; the marine natural products plakorsins A, B, and D and plakorsin D methyl ester; and the furan fatty acids 3D5 and hydromumiamicin.
Enantioselective Nickel-Catalyzed Alkyne-Azide Cycloaddition by Dynamic Kinetic Resolution
Liu, En-Chih,Topczewski, Joseph J.
supporting information, p. 5308 - 5313 (2021/05/04)
The triazole heterocycle has been widely adopted as an isostere for the amide bond. Many native amides are α-chiral, being derived from amino acids. This makes α-N-chiral triazoles attractive building blocks. This report describes the first enantioselective triazole synthesis that proceeds via nickel-catalyzed alkyne-azide cycloaddition (NiAAC). This dynamic kinetic resolution is enabled by a spontaneous [3,3]-sigmatropic rearrangement of the allylic azide. The 1,4,5-trisubstituted triazole products, derived from internal alkynes, are complementary to those commonly obtained by the related CuAAC reaction. Initial mechanistic experiments indicate that the NiAAC reaction proceeds through a monometallic Ni complex, which is distinct from the CuAAC manifold.
Copper-Catalyzed Cross-Nucleophile Coupling of β-Allenyl Silanes with Tertiary C-H Bonds: A Radical Approach to Branched 1,3-Dienes
Shan, Qi-Chao,Hu, Lu-Min,Qin, Wei,Hu, Xu-Hong
supporting information, p. 6041 - 6045 (2021/08/03)
Described herein is a distinctive approach to branched 1,3-dienes through oxidative coupling of two nucleophilic substrates, β-allenyl silanes, and hydrocarbons appending latent functionality by copper catalysis. Notably, C(sp3)-H dienylation proceeded in a regiospecific manner, even in the presence of competitive C-H bonds that are capable of occurring hydrogen atom transfer process, such as those located at benzylic and other tertiary sites, or adjacent to an oxygen atom. Control experiments support the intermediacy of functionalized alkyl radicals.
Copper(I)-Catalyzed Intramolecular Cyclization of o-Propargyloxy Diketopiperazines to Access Diverse Diazabicyclic and Spiro-Diketopiperazinochromanes
Armaghan, Mahsa,Balalaie, Saeed,Bijanzadeh, Hamid Reza,Frank, Walter,Manavi, Bita,Rominger, Frank,Tejeneki, Hossein Zahedian
supporting information, p. 4190 - 4196 (2021/08/06)
In this report, two distinctive intramolecular cyclizations of o-propargyloxy diketopiperazines (achieved from a one-pot Ugi post-transformation) is achieved via a copper(I)-catalyzed intramolecular reaction of azomethine ylide and alkyne moiety. The presence of internal alkyne in the starting materials directed the reaction towards through [3+2]-cycloaddition, while terminal alkyne led to a spirocyclization reaction between azomethine ylide and terminal unsaturated C?C bond. This method offering an opportunity for the synthesis of challenging Diazabicyclics and Spiro-Diketopiperazinochromanes in high yields with exclusive diastereoselectivity. (Figure presented.).
Bi(OTf)3-catalyed One-pot Synthesis of α-Halo-β-amino Ketones and Acyl Aziridines from 3-Aryl Propargyl Alcohols
Zhang, Qinglin,Duan, Yongbin,Guo, Huifeng,Yang, Hong,Zhai, Jiulong,Li, Tiantian,Wang, Zhihai,Lu, Xiaolei,Wang, Yan,Yin, Yan
supporting information, p. 1832 - 1838 (2021/06/09)
A Bi(OTf)3-catalyed reaction of 3-aryl propargyl alcohols with sulfonamide and halogen source was firstly investigated, which provided a facile route for the synthesis of a large variety of α-halo-β-amino ketones. The key intermediates, β-amino
RET INHIBITORS, PHARMACEUTICAL COMPOSITIONS AND USES THEREOF
-
Paragraph 00383; 00395, (2020/07/06)
Provided herein are a RET inhibitor, a pharmaceutical composition thereof and uses thereof. In particular, provided is a compound having Formula (I) or a stereoisomer, a geometric isomer, a tautomer, an N-oxide, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof. Provided is a pharmaceutical composition comprising the compound, and uses of the compound and pharmaceutical composition thereof for the preparation of a medicament, in particular for treatment and prevention of RET-related diseases and conditions, including cancer, irritable bowel syndrome, and/or pain associated with irritable bowel syndrome.
Chemoselective Hydroboration of Propargylic Alcohols and Amines Using a Manganese(II) Catalyst
Brzozowska, Aleksandra,Zubar, Viktoriia,Ganardi, Ruth-Christine,Rueping, Magnus
supporting information, p. 3765 - 3769 (2020/04/15)
The first manganese-catalyzed hydroboration of propargylic alcohols and amines as well as internal alkynes is reported. High regio- and stereoselectivity is achieved by applying 2 mol % of a manganese precatalyst based on the readily accessible bis(imino)pyridine ligand and MnCl2 as metal source. Propargylic alcohols and amines, as well as symmetric internal alkynes, were efficiently converted into the corresponding functionalized alkenes, which can serve as important and valuable intermediates for further synthetic applications such as cross-coupling reactions.
Photocatalyzed Diastereoselective Isomerization of Cinnamyl Chlorides to Cyclopropanes
Dykstra, Ryan,Gutierrez, Osvaldo,Martin, Robert T.,Tambar, Uttam K.,Troian-Gautier, Ludovic,Xu, Bin
supporting information, p. 6206 - 6215 (2020/04/27)
Endergonic isomerizations are thermodynamically unfavored processes that are difficult to realize under thermal conditions. We report a photocatalytic and diastereoselective isomerization of acyclic cinnamyl chlorides to strained cyclopropanes. Quantum mechanical calculations (uM06-2X and DLPNO), including TD-DFT calculations, and experimental studies provide evidence for the energy transfer from an iridium photocatalyst to the allylic chloride substrate followed by C-Cl homolytic cleavage. Subsequent Cla￠ radical migration forms a localized triplet 1,3-diradical intermediate that, after intersystem crossing, undergoes ring-closing to form the desired product. The mild reaction conditions are compatible with a broad range of functional groups to generate chlorocyclopropanes in high yields and diastereoselectivities. A more efficient process is developed by addition of a catalytic amount of a nickel complex, and we propose a novel role for this cocatalyst to recycle an allyl chloride byproduct generated in the course of the reaction. The reaction is also shown to be stereoconvergent, as an E/Z mixture of cinnamyl chlorides furnish the anti-chlorocyclopropane product in high diastereoselectivity. We anticipate that the use of a visible light activated photocatalyst to transform substrates in combination with a transition metal catalyst to recycle byproducts back into the catalytic cycle will provide unique opportunities for the discovery of new reactivity.
