Total Synthesis Of Cephalosol And Aquatolide/Pd-Catalyzed Stereoselective Synthesis Of1,3-Amino Alcohols

We focused our research interest on total synthesis of Cephalosol and Aquatolide, stereoselective synthesis of1,3-amino alcohols by the Pd-catalyzed cyclization of trichloroacetimidates. This thesis consists of the following three chapters:Chapter one:Total Synthesis of Cephalosol.A concise and efficient total synthesis of Cephalosol has been completed (5steps from known ester,39%overall yield). We obtained4-bromoisocoumarin fragment by6steps starting from3,5-dimethoxy aniline, then transformed4-bromoisocoumarin into ABC tricyclic skeleton structure through sequential Suzuki coupling/intramolecular oxo-Michael addition, finally completed the total synthesis of Cephalosol by further functional group transformation. Cu(II)-promoted haloisocoumarin formation and sequential Suzuki coupling/intramolecular oxo-Michael addition are worth noting for the current strategy.Chapter two:Stereoselective Synthesis of1,3-Amino Alcohols by the Pd-Catalyzed Cyclization of Trichloroacetimidates.The synthesis of4-vinyl-5,6-dihydro-1,3-oxazines, precursors of1,3-aminoalcohols, using the palladium-catalyzed cyclization of trichloroacetimidates was reported. We tried17substrates with up to95%yield and up to>20:l diastereoselectivity. The reaction favored the formation of the thermodynamic4,6-cis-isomers which were identified by X-ray diffraction. Chemoselective hydrolysis of the resulting5,6-dihydro-1,3-oxazines was also investigated.Chapter three:Total Synthesis of Aquatolide.In this chapter, we described the idea and method of the synthesis of natural product Aquatolide featuring Diels-Alder reaction, Wolff rearrangement, ring-closing metathesis reaction. In the process of implementation, we explored two practical synthetic routes based on the symmetry of the molecular skeleton.In the first route, we got Corey ketone by nine-step starting from norbornadiene, then constructed the gem-dimethyl, diazo in carbonyl a position, performed Wolff rearrangement to get four-membered ring skeleton. In this route alkylation in carbonyl a position is underway.In the second route, we obtained gem-dimethyl five-membered ring lactone fragment by15steps starting from norbornadiene, further transformed double bond into diazo, performed Wolff rearrangement to get four-membered ring skeleton, we want to get diene compound undergoing further modification, then complete the synthesis of Aquatolide by RCM reaction.