echemi logo
Product
  • Product
  • Supplier
  • Inquiry
    Home > Angelw: Pd / Cu co catalysis for selective heck Sonogashira coupling

    Angelw: Pd / Cu co catalysis for selective heck Sonogashira coupling

    • Last Update: 2019-12-01
    • Source: Internet
    • Author: User
    Search more information of high quality chemicals, good prices and reliable suppliers, visit www.echemi.com
    Because of their special stability, reactivity and biological activity, organofluorine compounds have been widely used in pharmaceutical chemistry and agricultural chemistry On the other hand, chiral 3,3-disubstituted indolones are widely distributed in natural products and active molecules, which are important structures Therefore, it is of great significance to develop a method to synthesize 3,3-disubstituted indole ketones containing fluorine The introduction of fluorine atoms may lead to new biological properties of indole ketones In fact, the introduction of fluorine atom or trifluoromethyl group into C3 position of indolones can increase their biological activity Although the asymmetric synthesis of 3-fluoro-substituted indolones has been reported, the introduction of trifluoromethyl into the C3 position of indolones and the formation of fourth-order carbon are very limited The asymmetric free radical trifluoromethylation method recently reported by katayev's group is the only method so far used to synthesize such compounds In recent years, the intermolecular asymmetric Heck reaction between aniline linked aromatic halides and alkenes is an effective method for the synthesis of chiral indole ketones However, in these asymmetric reactions, only alkenes with alkyl or aryl substitution participate in the reaction, and alkenes with trifluoromethyl substitution can not be effectively cyclized In fact, the studies on the Heck reaction involving trifluoromethyl substituted alkenes have been less, which is due to the potential β - fluorine elimination reaction Therefore, it is difficult to develop the heck type asymmetric cyclization with trifluoromethyl substituted alkenes to construct quaternary carbon centers Recently, the research team of Shaozhong Ge and Yixin Lu of National University of Singapore reported the asymmetric cascade heck cyclization / Sonogashira coupling reaction catalyzed by Pd / Cu, and synthesized a series of trifluoromethyl substituted chiral indolones In addition, other alkenes substituted by alkyl or aryl group can also get the target product with high EE value The related research results were published in angelw Chem Int ed (DOI: 10.1002/anie.201913148) (source: angelw Chem Int ed.) firstly, the author selected o-iodoacrylamide compound 1a and phenylacetylene 2A as template substrate for condition optimization (Table 1) Through the optimization of reaction conditions such as chiral ligand, solvent, alkali and temperature, the author determined the optimal reaction conditions: (η 3-c3h5) PdCl] 2 as palladium source, Cui as copper source, L4 as chiral ligand, DABCO as alkali, tert butanol as solvent, silver phosphate as additive, the substrate reacted at 80 ℃ for 20 hours, and the final yield was 75% and 97% ee It's worth the target product (source: angelw Chem Int ed.) after determining the optimal reaction conditions, the author expanded the substrate range of the reaction (Table 2) The substituents on the N atom can be methyl, PMB or benzyl The substitution of benzene ring can be halogen, methyl and methoxy In addition, alkyl and aryl terminal alkynes can participate in the reaction (source: angelw Chem Int ed.) there was almost no research on the application of this method to the construction of indolones with quaternary carbon centers before, so the author further explored the o-iodoacrylamides without trifluoromethyl substituted alkenes (Table 3) After the optimization of the reaction conditions, L2 was chosen as the chiral ligand, and the reaction had good functional group tolerance Methoxymethyl, siloxyether, chlorine, bromine, cyano and ester groups were all compatible with the reaction conditions (source: angelw Chem Int ed.) in order to illustrate the practicability of the reaction, the author carried out the following transformation (scheme 1) of the product, including: 1) the removal of the protective group on the N atom; 2) the removal of the silicon protective group in the product; 3) the cyclization reaction of the triple bond with the benzene ring in the parent nucleus of indole ketone; 3) the generation of chiral aldehydes through the semi reduction ozonation process; 4) The enantioselective synthesis of 5-HT 6 / 7 receptor antagonist egis-12233 was achieved (source: angelw Chem Int ed.) Summary: the GE and Lu research groups have developed a highly enantioselective method to synthesize indolones with quaternary carbon centers (including those with trifluoromethyl substitution) The heck / Sonogashira process catalyzed by Pd / Cu has good enantioselectivity and functional group tolerance, which provides a good method for the synthesis of indolones.
    This article is an English version of an article which is originally in the Chinese language on echemi.com and is provided for information purposes only. This website makes no representation or warranty of any kind, either expressed or implied, as to the accuracy, completeness ownership or reliability of the article or any translations thereof. If you have any concerns or complaints relating to the article, please send an email, providing a detailed description of the concern or complaint, to service@echemi.com. A staff member will contact you within 5 working days. Once verified, infringing content will be removed immediately.

    Contact Us

    The source of this page with content of products and services is from Internet, which doesn't represent ECHEMI's opinion. If you have any queries, please write to service@echemi.com. It will be replied within 5 days.

    Moreover, if you find any instances of plagiarism from the page, please send email to service@echemi.com with relevant evidence.