echemi logo
Product
  • Product
  • Supplier
  • Inquiry
    Home > Angelw: organic catalytic enantioselective [10 + 4] cycloaddition reaction

    Angelw: organic catalytic enantioselective [10 + 4] cycloaddition reaction

    • Last Update: 2018-08-29
    • Source: Internet
    • Author: User
    Search more information of high quality chemicals, good prices and reliable suppliers, visit www.echemi.com
    Cycloaddition reaction is a simple and controllable synthesis strategy, and has been widely used in the construction of chiral ring structures Among them, Diels alder reactions and dipolar cycloaddition reactions involving 6 π electrons are of great value, and many enantioselective catalytic systems have been reported The high-order cycloaddition reactions have great potential in the construction of complex ring skeleton Due to the challenges in position selectivity and stereo control, they have not been fully explored At present, researchers have only realized the high enantioselectivity of [6 + 2] and [8 + 2] cycloaddition reactions Recently, the first stereoselective [10 + 4] cycloaddition reaction between aminoisobenzofurane and diene without electron was reported by Karl Anker J ü rgensen group of Aarhus University in Denmark Relevant articles were published on angelw Chem Int ed (DOI: 10.1002 / anie 201807830) In the enantioselective [8 + 2] cycloaddition of aminoisobenzofurane and Nitroalkenes (angew Chem Int ed 2018, 57, 1246-1250), which was developed in the early stage of J ü rgensen group, the calculation results show that [10 + 4] cycloaddition products may become the intermediates with favorable kinetics (scheme 1) Subsequently, the possibility of enantioselective [10 + 4] cycloaddition was explored (source: angelw Chem Int ed.) in the early stage of the study, the author investigated the feasibility of Diphenylprolinol silica ether 3A (20 mol%) to catalyze the reaction of 1h-indene-2-formaldehyde 1a and diene 2A (1.5 equivalent) in CDCl3 At first, however, there was no target product Then, the 3-phenyl substituted indene 1b can react to obtain a single non enantiomer 4B with high yield and enantioselectivity Then, through the screening of catalysts, additives, solvents and other conditions, the author found that in the presence of molecular sieves (MS), basic alumina (f) and p-methoxybenzoic acid (p-meo-ba, 20 mol%), catalyst 3B can promote the reaction to cycloaddition product 4B (entry 7) with 69% yield and 92% ee value The yield of the product can be further improved and excellent enantioselectivity (entry 10) can be maintained after the reaction of substrate with 3B catalyst for 20 hours (source: angelw Chem Int ed.) then, under the optimal reaction conditions, the author examined the scope of application of the substrate (scheme 2) The 1h-indene-2-formaldehyde-1 with different electronic properties, such as phenyl, naphthyl and heterocyclic groups, can form [10 + 4] cycloadduct 4b-4j in high yield and high enantioselectivity The product 4k-4n can also be obtained in high yield and high enantioselectivity from indene-1 with methoxy, chlorine and methyl substituents on the benzene ring On the other hand, the range of 4 π compound 2 is also very wide The substrate 2 containing halogen, electron donor and electron acceptor group substituted phenyl ketone and methyl ketone can all react smoothly to obtain the cycloaddition product 4O - 4R, which has good to high yield and excellent enantioselectivity; the enantioselectivity of the product is reduced after ketone is converted into ester or cyano group (source: angelw Chem Int ed.) finally, the author explored the source of enantioselectivity of the product When 3B was used as catalyst, acid additive and water had a significant effect on the enantioselectivity of the reaction (Table 1) It is speculated that this is due to the formation and distribution of two rotational isomers, int-ia / int-ib, in the intermediate of aminoisobenzofurane (scheme 4) Under the optimized conditions, the removal of water may lead to the loss of reversibility of imine ions, thus eliminating the balance between int-ia and int-ib, thus having a positive impact on the enantioselectivity of the reaction From the absolute configuration of [10 + 4] cycloadduct 4, the reaction is mainly through int-ia, but the calculation results show that the energy of int-ib is lower This shows that under the optimized reaction conditions, the formation of int-ia is controlled by kinetics In order to carry out further research, the process of 4B and ent-4b generated from int-ia and int-ib was analyzed and calculated by using the reaction pathway The author thinks that int-ib is unlikely to form 4B near diene 2a from the side with steric hindrance The pathway to form 4B contains the intermediate with higher energy and lower energy barrier, while the pathway to form ent-4b contains the intermediate with lower energy and higher energy barrier Both of them have reasonable reaction energy barriers at room temperature The free energy calculation results show that the enantioselectivity is not determined by the conjugation addition of 2, but by the kinetic tendency of the formation of the intermediate int-ia (source: angelw Chem Int ed.) conclusion: the first case of catalytic [10 + 4] cycloaddition was developed by Karl Anker J ø rgensen The results of experiment and calculation show that the stereoselectivity of the reaction comes from the formation of amino isophene controlled by kinetics High yield, high enantioselectivity, enantioselectivity and a wide range of substrates make this method very valuable in the construction of complex and enantiomeric enriched skeletons.
    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.