The Synthesis And Reaction Of Germatranes

The construction of carbon-carbon bonds of biaryl rings is an important tool in modern organic synthesis.This type of carbon-carbon bonds is widely found in many natural products,bioactive drug molecules and agrochemicals.Therefore,in the past few decades,researchers have done a lot of work on the construction of carbon-carbon bonds of the biaryl ring.With the development of Pd chemistry,a series of aryl nucleophiles(Mg,Zn,Si,Sn,B,etc.)have been developed in the synthesis of biaryl ring compounds,and for their practicability,corresponding reaction was named after their most leading contributors.In the first chapter,we outlined a series of nucleophiles used in biaryl ring compounds,including Grignard reagents,zinc reagents,silicon reagents,tin reagents,boron reagents,and Ge reagents.Based on the relevant background,we recognize the lack of research on Ge reagents and accurately understand the key issues that restrict the development of these reagents.Compared with other nucleophiles,Ge is a group 14 element between Si and Sn,and its study as an aryl nucleophile is correspondingly less.This may be due to the fact that the electronegativity of Ge is high relative to Si and Sn,so its activity as a nucleophile is correspondingly low.In the second chapter,we synthesized a class of Ge reagents with novel structures.The coupling activity of this Ge reagent has been significantly improved by the transannular nitrogen-germanium coordination effect,Thorpe-Ingold Effect,and the incorporation of rigid benzo-aromatic ring structures.The improvement.Moreover,the reagent is stable to water and air,and is a white solid or crystal at room temperature,which is very convenient for storage.Another key issue that limits the use of Ge reagents is the difficulty in introducing them.In the process of introducing Ge reagents,predecessors usually need to use lithium reagents,GeCl4,GeCl2 and other reagents,and these reagents preparation conditions are more demanding and difficult to store.In the third chapter,we synthesized two kinds of Ge-H and Ge-CI synthons by using simple GeO2 as the starting material.According to the history of the development of boron reagents,we have realized the use of Ge-CI coupling with aryl format reagents to introduce Ge reagents.Furthermore,we have realized palladium-catalyzed coupling of Ge-H with aryl iodides,aryl bromides,aryl trifluoromethanesulfonates,which opens up new ways for the introduction of Ge reagents.Among them,the coupling of Ge-H and aryl halide can be compatible with various functional groups,and it also has a good reaction effect on heteroaryl ring halides,which lays a solid foundation for the application of Ge reagents in the synthesis of drug molecules.Through our development of the Ge reagent introduction method,we have obtained a series of aryl Ge reagents.What we need to do next is to explore the reactivity of these Ge reagents with different functional groups.In the fourth chapter,we studied the coupling of aryl Ge reagents with aryl halides and synthesized a series of biaryl ring compounds.The coupling reaction has a wide range of functional group compatibility.A variety of biaryl ring compounds that have never been reported before have been prepared by this method.In the work of Chapter 5,we explored the application of aryl Ge reagents in drug synthesis and its compatibility with modern synthetic methods.Using the characteristics of aryl Ge reagents,we designed it to be used to iteratively synthesize drug molecules GABAA receptors.In addition,we have found that Ge reagents are well tolerant to oxidative conditions and can be highly compatible with high-valent iodine carbon-hydrogen bond activation reactions.Finally,we studied the selectivity and compatibility of the Ge reagents and the Suzuki reaction and found that it is perfectly compatible with the reaction conditions of the boronic acid pinacol ester and the boric acid methylimine diacetate,and can be used as a masking nucleophile.