Synthesis And Study Of Chiral Nitrogen-hetero Benzospiro Derivatives

Chiral and spiro compounds have been widely used as drugs, pesticides and functional materials, because most of them have shown excellent performance. Recently, researches on these particular compounds have become very active, and are still getting more and more attention from the public.In this thesis, we have designed and synthesized a series of nitrogen-hetero benzospiro compounds which contain chiral centers. By using (R)-2-methyloxirane as the start material, we first synthesized compound4R via4steps in35%overall yield. Compound4R was reduced by hydrogen to give compound5R. Addition of compound4R with Br2and the subsequent elimination with a base afforded compound7R in85%yield. Compound7R was reacted with ethyl carbonochloridate and then the intermediate underwent hydrolysis under base condition to give compound8R. Compound4R was reacted successively with9-BBN and H2O2to give compound10R. Compound12R could be obtained from compound7R through a coupling reaction. Compound12R was reduced by hydrogenation to give compound13R. When compound12R was treated with silica gel, it decomposed to give compound14R. Compound7R was transformed to compound15R through a Suzuki reaction. Compound7R was reacted with3-(methoxycarbonyl)phenylboronic acid to give compound16R. Hydrolysis of compound16R furnished compound17R.We designed the synthetic routes of these compounds, and optimized them based on our extensive work. By analyzing the unusual experimental phenomena, we found new ideas to synthesize some new compounds.