Dissertation > Mathematical sciences and chemical > Chemistry > Organic Chemistry > Heterocyclic compounds > Containing five pairs or more different atoms of heterocyclic

1 isoxazoline benzo oxa Zhuo Synthesis study the homogeneous of Au ( I ) catalysis in organic synthesis applied research

Author WangGuan
Tutor WangQuanRui
School Fudan University
Course Organic Chemistry
Keywords Nitrile oxide dipole The isoxazoline and to benzoxepin Zhuo [ 42 ] cycloaddition reaction Catalyzed by Gold Nonclassical carbocation Rautenstrauch rearrangement reaction
CLC O626.2
Type PhD thesis
Year 2011
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Benzoxepin Zhuo compounds is a very important class of compounds, widely present in nature in the form of alkaloids. These compounds have better physiological activity, mainly in the clinical aspects of the central nervous system (CNS) activity. Makes people more and more pressure to speed up the process of modern urbanization, resulting in an increasing number of people have depression tendencies. Natural compounds of this class, regardless of the quantity or activity are increasingly unable to meet the demand of the people. Organic hotels and pharmacologist by an organic synthesis method which requires the preparation of novel such compounds, it is desirable to be able to obtain the better the antidepressant activity of drugs. The study mainly include two aspects: first, through the modification of the benzene ring or oxa Zhuo ring to build a new treatment of central nervous system drugs. Second, by introducing a third ring on benzoxepin Zhuo bicyclic system to build the tricyclic ring system. See from the literature study using the first method. We use the second method to study the synthesis of novel CNS drugs. Showed better clinical antidepressant activity of another - class of heterocyclic compounds isoxazoline compounds, so we hope to better structural units of the two active fusion construct isoxazoline and benzo oxa the Zhuo compounds, expect more novel tricyclic compounds. Gold catalysis is one of the hot topics in the field of organic chemistry research today. Especially the last decade, the homogeneous gold catalysis has become to build unknown structure and the development of new organic reaction mechanism powerful means. Wherein the cycloaddition reaction and the ring isomerization reaction is the reaction of two types of wide concern. Because of this, in this paper we study between a homogeneous gold-catalyzed allene ether and diene cycloaddition reaction, and a new homogeneous gold catalysis Rautenstrauch rearrangement reaction, and the reaction mechanism were depth. In the first chapter of this thesis, two topics covered by the papers of the literature review. First introduced isoxazoline and benzoxepin the research significance Zhuo compounds, listed their synthesis. We then introduced from the background of the gold-catalyzed and homogeneous gold catalysis [42] cycloaddition reaction of the status quo both the corresponding field research background. Finally, we introduce the development status of the homogeneous gold catalysis Rautenstrauch rearrangement reaction, the ingenious application of the of homogeneous gold catalytic reaction in the total synthesis of complex natural products. The first in the second chapter of this thesis through the phenylacetaldehyde prepare a series of 1 - (4 - bromo-1 - butenyl) - benzene (45). Then by them and salicyl aldehyde compound (46) was prepared by etherification reaction of 2 - (4 - phenyl-3 - butene-yloxy) - benzaldehyde (47), then after the oximation series of benzene carbaldehyde oxime compound (48). Finally, benzaldehyde oxime (48a) as the template substrate, and reaction conditions reported in the literature, one step process for the preparation of the tricyclic ring system, - isoxazoline and heteroaryl Zhuo benzoxazepine compound (49) to obtain the target product. The reaction is achieved by 1,3 - dipolar cycloaddition reaction under mild conditions, good yield. In the third chapter of the thesis, we introduced the gold-catalyzed allene ether and diene between [42] cycloaddition reaction. First, we prepared a series of differently substituted alkenyl ether (77). Then we select 77a and cyclopentadiene to be screened as a template reaction substrate of the reaction conditions. Then we expanded the substrate in the reaction, to demonstrate the versatility of the reaction. Then we-depth study of the reaction mechanism. Studies have shown that the reaction is likely to be the addition reaction carried out by a collaborative [42] ring. We successfully implemented diene body 78 is captured in the reaction system of gold catalyst and 77 in situ generated allyloxy fork oxygen onium ion Intermediate 84 normal electron demand Diels-Alder reactions, the high selectivity in the synthesis of substituted cyclohexene ether compound 79. Z configuration based cycloaddition product 79i-n substituted cyclopentadienyl 78b-d for containing an electron donor group, the reaction is carried out with a very good yield. For the cyclopentadienyl 78a, the reaction was obtained in good yield Z configuration based cycloaddition product 79a-g. Containing an electron donor group substituted open chain diene body 78E-J, the reaction can be the middle yield selectively obtained 79o-z of the cycloaddition reaction product of Z configuration. The reaction is carried out in methylene chloride, the catalyst amount is small, the room temperature for 3 minutes to complete. The method has a high yield, choose mild conditions, substrate applicability good advantages. In the fourth chapter of this paper, we study a homogeneous gold catalysis Rautenstrauch rearrangement reaction. We first introduced a series of cyclopropyl propargyl 32 preparation methods. Then, by the screening of the conditions the reaction substrate expansion. Then our in-depth study of the reaction mechanism, to prove the existence of nonclassical carbocation reasonable. A ring on the whole of the gold catalytic homogeneous Rautenstrauch rearrangement reaction has the efficient, rapid and mild reaction conditions, can be easily synthesized functionalized ketene class compound 91. We also synthesized an optically active substrate cyclopropyl propargyl (1S, 2S) -120, and the bottom was used to study the chiral transmission effect of the rearrangement reaction. Through the filter on the reaction conditions, to achieve the transfer of the chiral information to a certain extent, synthetic ring having optical activity has enone (S) -121 and ring octenones 122. The absolute configuration of the product by measuring the circular dichroism and theoretical fit OK. Chapter 5, the experimental part of the record the methods and steps of the synthesis of all compounds were characterized by IR, NMR, GC-MS and HRMS method. Part of a typical new compounds also attached a spectrogram.

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