Studies On Asymnletrie Schmidt Reaction And Synthesis Of Calyciphylline A Type Alkaloids

This thesis includes two parts:we introduced recent progress on asymmetric Schmidt reaction and our studies on the enantioselective desymmetrization in an intramolecular Schmidt reaction in the first part; the second part consists of recent progress on the syntheses of Calyciphylline A type alkaloids, our exploration on tandem semipinacol rearrangement/aldol reaction, the construction of A-D-E tricyclic core of Calyciphylline A-type alkaloids and the syntheses of daphniyunnine B using tandem semipinacol rearrangement/aldol reaction.Part I:Alkaloids containing azaquaternary pyrroloazepine skeletons are an important class of bioactive molecules in nature. How to directly and enantioselectively construct the azaquaternary pyrroloazepine skeleton remains a challenge. An intramolecular Schmidt reaction of prochiral azido1,3-diketones could concisely construct azaquaternary pyrroloazepine compounds. However, recent efforts to achieve enantioselective symmetry breaking of azido1,3-diketones using this reaction failed when chiral Lewis acids were used. In this part, we described the first successful enantioselective desymmetrization in an intramolecular Schmidt reaction of prochiral azido1,3-hexanediones, which was promoted by1,1’-bi-2-naphthal (BINOL)-derived N-triflylphosphoramides. Although only moderate enantioselectivities and yields were obtained, it successfully demonstrates for the first time that enantioselective desymmetrization of symmetric azido1,3-diketones via an intramolecular Schmidt reaction is a viable process using a chiral Bransted acid. We also tried enantioselective desymmetrization in an intramolecular Schmidt reaction of prochiral azido1,3-hexanediones by using chiral Lewis acid as promoter, however, the enantioselectivities were poor.Part II:6-Substituted spiro[4.5]decanes which contain a spirocyclic all-carbon quaternary center, as the key structural motifs, commonly exist in Calyciphylline A-type alkaloids. How to directly and rapidly construct this unit is the key and challenging step for the syntheses of these molecules. In this part, we have developed a tandem semipinacol rearrangement/aldol reaction of trimethylsilane-protected vinylogous a-ketols with aldehyde or dimethyl acetals.6-Substituted spiro[4.5]decane-1,7-diones could be easily and rapidly synthesized by this protocol. Subsequently, the A-D-E tricyclic core of Calyciphylline A-type alkaloids has been rapidly constructed for the first time. Although the total synthesis of daphniyunnine B using tandem semipinacol rearrangement/aldol reaction was not finished now, it laid a firm foundation for the total synthesis.