Study On The Synthesis Of Oxidized Indospiro-2,3-dihydrofuran Ring Compound

A large number of natural or synthetic organic products and highly biologically active substances contain the skeleton of the oxyindole spiro ring.The oxyindole spiro skeleton with multiple chiral centers is a key component of some drug molecules.Therefore,it is very important to develop some efficient and concise methods to synthesize compounds containing the oxyindole spiro skeleton.The dicyano compound with two strong electron-withdrawing groups can activate the adjacent C atoms to make it easier to form carbanions.Cyclization reactions can easily occur after attacking the electrophile,which is useful for constructing various types of spirographs.Cyclic compounds have unique advantages.In this paper,we successfully synthesized many functionalized oxyindospiro-2,3-dihydrofuran ring compounds based on the[3+2]cycloaddition reaction between the isatin-derived dicyano compound and the compound with high active carbonyl group.Carried out the following research work.In Chapter 1,This chapter summarizes the research progress of oxyindole spiro compounds,and introduces the two main methods used by chemists to synthesize such compounds in recent years.In Chapter 2,We developed a[3+2]cycloaddition reaction between isatin-derived dicyano compounds and compounds with highly active carbonyl groups,and synthesized a series of optically active oxyindospiro-2,3-dihydrofuran rings Compound.Our substrate-based polarity reversal strategy uses quinine-derived bifunctional thiourea as a chiral catalyst,and THF as an organic solvent.The reaction at-30 ~0C can achieve good yields(up to 69%yield)and ideal Enantioselectivity(up to 95%ee),extremely high diastereoselectivity(up to>99:1 dr)to obtain the target compound.The reaction substrate has wide applicability and high atom utilization.This is also the first example of asymmetric synthesis of bisoxindole spiro-2,3-dihydrofuran ring compounds,which is of great significance to the development of asymmetric synthesis of such compounds.In Chapter 3,We have developed a green and efficient synthesis of an oxyindospiro-2,3-dihydrofuran ring compound with excellent structure and potential biological activity in the water phase.This reaction has an excellent yield(up to 96%yield)and Diastereoselectivity(up to 99:1 dr).The reaction uses water as a solvent,the reaction can be quickly completed in boiling water,the reaction is extremely efficient,and the target compound can be obtained by simple post-treatment,which provides a simple and efficient synthetic route for the synthesis of oxidized indospirofuran ring compounds.In Chapter 4,Summary of the full text:Through the research of this paper,we have realized the asymmetric synthesis of oxidized indospiro-2,3-dihydrofuran ring compounds with organic small molecule catalysts.At the same time,A green and efficient method for synthesizing such compounds is proposed.