| This thesis mainly aimed at the construction of[5.6]spirooxindles and2,3-disubstituted benzofurans and the studies on the total synthesis of the natural product Laevinoids A.Chap.1 Facile synthesis of thiochromanyl-spirooxindoles via K2CO3 catalyzed tandem sulfa-Michael/Aldol reactionSpirooxindoles are widely existed active units in natural products and drug molecules,and it is also a hot spot in organic synthesis.Isatin derived unsaturated esters are used as an important synthetic building block to construct a series of complex natural products included five-or six-membered spirooxindole of all-carbon or heterocycle.With carefully literature research,we found that the thio[5.6]spirooxindole skeleton was rarely been reported.Therefore,it is necessary to develop a novel and efficient method to construct the thio[5.6]spirooxindoles.Based on the previous analysis,we herein present a convenient method to construct thiochromanyl spirooxindole skeleton through K2CO3 catalyzed tandem sulfa Michael/Aldol reaction in one step,the structure of product was unambiguously confirmed by X-ray single crystal analysis.This cascade protocol not only provided a versatile,economical access to a range of potential bioactive compounds under very mild and operationally simple reaction conditions,but also had high efficiencies（up to 88%）and good diastereoselectivities（>20:1）.Moreover,gram-scale performance showed promising for application in biologically active and medicinal chemistry.We also study the asymmetric version of this protocol in 60%ee.Chap.2 Synthesis of 2-substituted 3-chlorobenzofurans and 2-substituted3-phenylthiobenzofurans via Lewis acid-mediated nucleophilic annulation of isatin-derived propargylic alcohols2,3-Disubstituted benzofuran represent an important class of heterocyclic compounds because they are the key structural motifs in a wide array of biologically relevant molecules.Unique skeleton structures,diverse biological activities and great medicinal value attract the focus of chemists and pharmacists.Natural products containing 2,3-disubstituted benzofuran skeleton exhibit good biological activity such as anti-tumor,anti-fungal,anti-oxidant,anti-inflammatory and so on.After previous literature research,we know that there have been a lot of studies on the construction of benzofuran skeletons,but the construction of 2,3-disubstituted benzofuran skeleton,especially the 3-chlorobenzofurans and 3-sulfenylbenzofurans is still a big challenge.We have successfully developed an interesting method for the construction of2-substituted 3-chlorobenzofuran and 2-substituted 3-sulfenylbenzofuran architectures via a Lewis acid mediated reaction of isatin derived propargylic alcohols through a sequential Meyer–Schuster rearrangement/nucleophilic addition/intramolecular annulation.Through a control experiment,we also conducted an in-depth discussion of the mechanism of this reaction.And we also found that by choosing the type of substrates,we can obtain thiobenzopyran compounds.The cost-effective reaction system,good functional group tolerance,ambient reaction conditions,and operational simplicity of this strategy enable a sustainable and convenient alternative for the synthesis of 3-chlorobenzofuran and 3-sulfenylbenzofuransChap.3 Studies on the total synthesis of natural product Laevinoid ALaevinoid A is one of two special structures of diterpenoids isolated from the branches and leaves of C.laevigatus from Hainan Island in 2013 by the Yue group.The authors determined their configuration by a series of analytical methods such as high resolution mass spectrometry,two-dimensional nuclear magnetic and single-crystal X-ray diffraction studies.Laevinoids A and B are the first examples of a new rearranged ent-clerodane skeleton with a unique 3/5 bicyclic motif of the clerodane family.With a view to its unique molecular structure,our group carried out the studies on the total synthesis of Laevinoids A.Firstly,the cyclopropanation reaction of ruthenium-catalyzed diazo compounds withα,β-unsaturated esters was studied by model reaction to construct B and C rings,but unfortunately,3/5 bicyclic skeleton compounds could not be obtained.Subsequently,we redesigned the synthetic route and in this route,we plan to use the intramolecular cyclopropanation and DA reaction as the key step to synthesis the Laevinoids A.The compound 3-11 was successfully obtained and synthesis of compound 3-12 and Laevinoid A are still in progress. |
