The Synthesis And Applications Of Tertiary Cyclopropyl Carbagermatranes

The cyclopropyl ring is ubiquitously found in drug molecules,serving as a bioisostere for an olefin due to its similar properties.One straightforward approach to the synthesis of cyclopropane homologues is cross-coupling reaction using preinstalled cyclopropyl reagents,which is often used in pharmaceutical chemistry research.Meanwhile,excellent balance between stability and reactivity of cyclopropyl boron reagents make it function as remarkable alternatives.Other nucleophiles have lower reactivity and cyclopropyl metal nucleophiles are difficult to be compatible with functional groups such as carbonyls and are sensitive to moisture and air.In Chapter 1,we summarize the synthesis and related properties of tertiary cyclopropyl nucleophilic reagents.In the following chapters,we dissertated the synthesis and application of tertiary cyclopropyl carbagermatranes.In chapter two,an efficient synthesis of tertiary cyclopropyl carbagermatranes by a zinc-mediated decarboxylative strategy of corresponding carboxylic acid NHydrox-Phthalimide ester(NHP ester)was described.The mechanism experiments show that NHP ester was likely first reduced to corresponding tertiary alkyl radical by Zn powder,further single electron reduction of the alkyl radical would give corresponding alkyl anion,which finally reacted with Ge-Br to afford tertiary cyclopropyl carbagermatranes as products.Subsequently,we have managed to achieved the cross-coupling reaction of tertiary cyclopropyl carbagermatranes with aryl bromide under palladium catalysis.In addition,the relative configuration of tertiary cyclopropyl carbagermatranes was well maintained in both reaction processes.Finally,we demonstrated the stability and orthogonality with boron reagents of tertiary cyclopropyl carbagermatranes.In chapter three,the cross-coupling reaction of tertiary tertiary cyclopropyl carbagermatranes with acyl chloride under palladium catalysis was further demonstrated.The coupling reaction between acyl chloride and nucleophiles is extensive and efficient,but research on cyclopropyl nucleophiles is limited.Although reaction of aryl chloride with secondary cyclopropyl boron reagents has been reported.Based on the work reported in Chapter 2,the scope of electrophiles was extended to acyl chloride,alkenyl and alkyl acyl chloride from aryl bromide.This is the first time to realize the coupling reaction of acyl chloride and tertiary cyclopropyl nucleophiles which are stable to moisture.This expansion of the scope allowed us to synthesize cyclopropyl derivatives from more natural products containing carboxyl groups.In chapter four,reaction of tertiary cyclopropyl carbagermatranes was extended to more complex Catellani reaction as termination reagent.The challenge of this strategy is that the termination step may be difficult to proceed due to excessive steric hindrance.The cross-coupling reaction between 2,6-disubstituted aryl electrophiles and tertiary cyclopropyl nucleophiles has hardly been reported before.Through palladium/norbornene co-catalysis,tertiary cyclopropyl carbagermatranes terminated reaction was achieved in the efforts of our group.The ipsocyclopropanation/ortho-alkylation product can be obtained by this strategy,which was difficult to accomplished before.Lastly,the ring opening of cyclopropane formally provided the open-chain tertiary alkyl termination product.