| The benzoxepine nucleus represents an important motif which occurs as alkaloids in nature, and exhibit a wide spectrum of biological activities. Nowadays many drugs in clinical which are used as therapy of centre neural system diseases contain a benzoxepine skeleton. With the modern quick urbanized course increasing number of citizens suffer from more or less depressed illness. So there is a need to develop new methods for the synthesis of novel analog. In the present, the two methods frequently exploited include the modification of the benzene ring on benzoxepine motif and addition of a third heterocycle ring to the benzoxepine. However, a literature survey suggests that the latter one has relatively less investigated. The reported methods include ring enlargement and intermolecular 1,3-dipolar cycloaddition, while the intramolecular cycloaddition less investigated. On the other hand, the isoxazoline motif also exhibits interesting biological activities. Therefore, the synthesis of unprecedented isoxazoline anellated benzoxepines constitute one of our research topics aimed at developing new tricyclic compounds with potential CNS activities.Nowadays, homogeneous gold catalysis has aroused considerable research efforteds in organic and theoretical communites. A literature survey revealed that the filed of gold catalysis has mainly been restricted on the use as heterogeneous catalysts for a long time. However, the situation has been changed since 1990s. Homogeneous gold catalysis has been recognized as a powerful synthetic tool to access unprecedented structural and mechanistic diversity in the past decade. In particular, Au-catalyzed intramolecular cyclizations and cycloisomerization has been extensively investigated. Thus in the present dissertation, we studied on the cationic gold(I)-catalyzed intermolecular [4+2] cycloaddition between dienes and allenyl ethers as well as gold catalysis homo-Rautenstrauch rearrangement.The first chapter is a brief review. The synthesis and application of benzoxepinoisoxazoles and related heterocycles were summarized. The homogeneous gold catalyzed synthetic transformations with emphasis on gold-catalyzed [4+2] cycloaddition and the gold catalyzed homo-Rautenstrauch rearrangement were reviewed. The gold catalysis strategy that allows quick access to complex natured products was also discussed.In chapter 2, a series of 1-(4-bromobut-1-enyl)benzenes (45) were prepared from 2-phenylacetaldehyde. Williamson ether synthesis of salicyl aldehyde (46) with 45 afforded 2-(4-phenylbut-3-enyloxy)benzaldehydes (47). 2-((E)-4-phenylbut-3-enyloxy)benzaldehyde oxime (48) were prepared from 47 by condensation with hydroxyamine hydrochloride. In the presence of NaOCl,48a underwent intramolecular 1,3-dipolar cycloaddition to furnish the novel tricyclic compound 49a-f. The yields were generally moderate to good and the reaction condition was mild.In Chapter 3, we have succeeded in the gold(I)-catalyzed intermolecular [4+2] cycloaddition between dienes and allenyl ethers. The synthesis begin with the preparation of a series of allenyl ethers (77) from propargyl ethers. We chose the reaction of 77a and cyclopentadiene as a model to screen the optimal condition. Then the substrates were expanded to different types of allenyl ethers and dienes to investigate the scope and limitations of this cycloaddition. As for the mechanism of the cycloaddition, we postulated that they follow a concerted [4+2] cycloaddition. This work realized a Diels-Alder reaction with nomal electron-demand by trapping Au-stabilized allylidene oxonium 84 with diene 78. This methodology represents an unprecedented strategy to access unique cyclohexene derivatives 79. For cyclopentadienes that bear an electron-donatimg group 78b-d, the Z-configured products Z-79i-n were obtained in excellent yield. For the parent cyclopentadiene 78a, the reaction could also proceed smoothly in good yield. However, linear dienes substituted with electron-donating group 78e-j, furnished the Z-79o-z in moderate yields. This unique [4+2] cycloaddition proceeded in general at room temperature and went to completion in several minutes under a low dosage of catalysts.In Chapter 4, a new Au-catalyzed homo-Rautenstrauch rearrangement was developed. The work commenced with the synthesis of a series of cyclopropylpropargylic esters (32). Different cyclopropy alkynyl ester substrates 32 were investigated to study the scope and limitations under variable conditions. Then we focus on the mechanism of the Rautenstrauch rearrangement. The concept of carbocation was applied to account for the observed unusual reactivity of cyclopropylpropargylic esters 32. In general, the gold catalyzed rearrangement was highly efficient, rapid under mild conditions. In addition, enantiomerically enriched cyclohexenones (S)-121 was prepared by the gold-catalyzed cycloisomerization of optically active propargyl acetates (1S,2S-120). Although the rearrangements are cationic in nature, some degree of chirality transfer in these reactions suggests that gold-stabilized nonclassical carbocations with a certain configurational stability are involved. The absolute configurations of the products were determined by measurement and theoretical stimulation of their ECD.Chapter 5 is the experimental section, which record the experimental details of the synthesis. New compounds have been characterized by IR, NMR, GC-MS and HRMS analysis. |
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