Research Of The Chiral Benzo Spiroacetal Ketone Skeleton And Application Toγ-rubromycin Asymmetric Synthesis

In this thesis,we found cinchona-derived catalyst (DHQD)2AQN can catalyze the asymmetric halogenation of the a-carbon of carbonyl and SN2cycloetherification reaction and complete the enantioselective construction of bis-benzannelated spiroketal core of rubromycins. It consists of the following two parts:Chapter1. Synthesis and Application of Chiral Quaternary Ammonium Iodides as Novel Chiral Phase-Transfer CatalystsAccording to literature, a series of C2-symmetric chiral quaternary ammonium bromides6have been designed as a new synthetic chiral phase-transfer catalyst, and prepared from commercially available optically pure1,1-bi-2-naphthol as a basic chiral unit. The catalyst combine with the advantages of the PCT and the usage of hypervalent iodine reagents after Iodide replace the Bromide. we tested the catalysts whether they will work in some the reaction in asymmetric manner. In this thesis, we aims at the enantioselective construction of the bis-benzannelated spiroketal core of rubromycins. The exploration found some obvious achievements, which is worth to be deeply modified. This work is still undergoing.Chapter2.Research on synthesis of chiral benzo spiroketal skeleton and its application in asymmetric synthesis of γ-rubromycinBased on Chapter1, we screened out compound (DHQD)2AQN as catalyst for the asymmetric halogenation of the a-carbon of carbonyl and SN2nucleophilic attack intramolecular to achieve the cycloetherification reaction to enantioselectively construct bis-benzannelated spiroketal. Using NIS,NBS and DMDBH providing halogen source, bis-benzannelated spiroketal3-5fromed with moderate yield and highly enantioselective in the presence of catalyst. After optimizing the reaction conditions, we found the best condition and applied it to verified substrates and achieved a series of chiral spiroketals. We also used this condition in the cycloetherification of y-rubromycin and achieved with80%yield and93%ee. we have completed the asymmetric synthesis of y-rubromycin.