Concise Synthesis of Furo[2,3-b]indolines via [3,3]-Sigmatropic Rearrangement of N-Alkenyloxyindoles

被引:5
作者
Shevlin, Michael [1 ,2 ]
Strotman, Neil A. [1 ]
Anderson, Laura L. [2 ]
机构
[1] Merck & Co Inc, Dept Proc Res & Dev, 126 E Lincoln Ave, Rahway, NJ 07065 USA
[2] Univ Illinois, Dept Chem, 845 W Taylor St, Chicago, IL 60607 USA
基金
美国国家科学基金会;
关键词
N-hydroxyindole; 3,3]-sigmatropic rearrangement; heterocycle; hemiaminal; high-throughput experimentation; HIGH-THROUGHPUT EXPERIMENTATION; DRUG DISCOVERY; CHEMISTRY; ARYLHYDROXYLAMINES; PHYSOSTIGMINE; HETEROCYCLES; ARYLATION; METHYL;
D O I
10.1055/s-0040-1707250
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
A concise new synthetic route to furo[2,3-b]indolines has been developed by taking advantage of the reactivity of N-alkenyloxyindole intermediates. These compounds spontaneously undergo [3,3]-sigmatropic rearrangement followed by cyclization to form hemiaminals as single diastereomers. Tin-promoted N-hydroxyindole formation followed by conjugate addition to activated alkynes provides simple and modular access to a diverse array of N-alkenyloxyindoles and their corresponding furo[2,3-b]indolines. Microscale high-throughput experimentation was used to facilitate investigation of the scope and tolerance of this transformation and related studies on the nucleophilic aromatic substitution and rearrangement of N-hydroxyindoles with halogenated arenes have also been evaluated.
引用
收藏
页码:197 / 201
页数:5
相关论文
共 46 条
  • [1] Alshreimi A. S., 2020, ANGEW CHEM INT EDIT, V132, P15356
  • [2] Gold-Catalyzed Dearomatization of 2-Naphthols with Alkynes
    An, Juzeng
    Parodi, Adriano
    Monari, Magda
    Castineira Reis, Marta
    Silva Lopez, Carlos
    Bandini, Marco
    [J]. CHEMISTRY-A EUROPEAN JOURNAL, 2017, 23 (69) : 17473 - 17477
  • [3] Anderson LL, 2015, MOLECULAR REARRANGEMENTS IN ORGANIC SYNTHESIS, P431
  • [4] Chemistry and biosynthesis of clavulanic acid and other clavams
    Baggaley, KH
    Brown, AG
    Schofield, CJ
    [J]. NATURAL PRODUCT REPORTS, 1997, 14 (04) : 309 - 333
  • [5] High-Throughput Discovery and Evaluation of a General Catalytic Method for N-Arylation of Weakly Nucleophilic Sulfonamides
    Becica, Joseph
    Hruszkewycz, Damian P.
    Steves, Janelle E.
    Elward, Jennifer M.
    Leitch, David C.
    Dobereiner, Graham E.
    [J]. ORGANIC LETTERS, 2019, 21 (22) : 8981 - 8986
  • [6] The biology and chemistry of the zoanthamine alkaloids
    Behenna, Douglas C.
    Stockdill, Jennifer L.
    Stoltz, Brian M.
    [J]. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2008, 47 (13) : 2365 - 2386
  • [7] Microscale High-Throughput Experimentation as an Enabling Technology in Drug Discovery: Application in the Discovery of (Piperidinyl)pyridinyl-1H-benzimidazole Diacylglycerol Acyltransferase 1 Inhibitors
    Cernak, Tim
    Gesmundo, Nathan J.
    Dykstra, Kevin
    Yu, Yang
    Wu, Zhicai
    Shi, Zhi-Cai
    Vachal, Petr
    Sperbeck, Donald
    He, Shuwen
    Murphy, Beth Ann
    Sonatore, Lisa
    Williams, Steven
    Madeira, Maria
    Verras, Andreas
    Reiter, Maud
    Lee, Claire Heechoon
    Cuff, James
    Sherer, Edward C.
    Kuethe, Jeffrey
    Goble, Stephen
    Perrotto, Nicholas
    Pinto, Shirly
    Shen, Dong-Ming
    Nargund, Ravi
    Balkovec, James
    DeVita, Robert J.
    Dreher, Spencer D.
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 2017, 60 (09) : 3594 - 3605
  • [8] Direct Preparation of Benzofurans from O-Arylhydroxylamines
    Contiero, Fanny
    Jones, Kevin M.
    Matts, Edward A.
    Porzelle, Achim
    Tomkinson, Nicholas C. O.
    [J]. SYNLETT, 2009, (18) : 3003 - 3006
  • [9] Electrolytic Macrocyclizations: Scalable Synthesis of a Diazonamide-Based Drug Development Candidate
    Ding, Hui
    DeRoy, Patrick L.
    Perreault, Christian
    Larivee, Alexandre
    Siddiqui, Arshad
    Caldwell, Charles G.
    Harran, Susan
    Harran, Patrick G.
    [J]. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2015, 54 (16) : 4818 - 4822
  • [10] N-hydroxy indoles as flexible substrates in rearrangements -: a novel reaction with activated triple bonds
    Duarte, MP
    Mendonça, RF
    Prabhakar, S
    Lobo, AM
    [J]. TETRAHEDRON LETTERS, 2006, 47 (07) : 1173 - 1176