The Synthesis And Cross-Coupling Reactions Of Alkyl/Heterocyclic Germatranes

The construction of C-C bonds is one of the important tasks of organic chemists.The development of transition metal-catalyzed cross-coupling reactions to construct C-C bonds has a great impact on ma ny disciplines that involve organic molecules.In 2010,the Nobel Prize in Chemistry was awarded to the field of Pd-catalyzed cross-coupling which reflects the importance of this field.The cross-coupling reactions benefit from the diversity of nucleophiles involved in these reactions and abundant functional groups contained in these nucleophiles.Although sp2-hybridized nucleophiles have made great achievements in past decades,development of sp3-hybridized nucleophiles in cross-coupling reactions is quite slow.In addition,although there are many methods to construct biaryl skeletons,it is still difficult to synthesize complex heterocyclic compounds.We have attempted to develop a new sp3-hybridized nucleophile to strike a good balance between the stability and reactivity of alkyl nucleophiles.In the chapter 2,we have synthesized a series of alkyl carbagermatranes with good functional group tolerance,and successfully realized the Pd-catalyzed additive-free sp2-sp3 cross-coupling reactions of alkylcarbagermatranes with aryl electrophiles.Alkyl carbagermatranes exhibit high activity in a series of sp2-sp3 cross-coupling reactions.Mechanism studies indicate that the transmetalation of alkylcarbagermatranes is likely to undergo a "SE2(open)Inv"transition state under standard coupling conditions.In addition,we have further explored the stability of alkylcarbagermatranes.Studies have shown that alkylcarbagermatranes can retain intact in a variety of reactions.Finally,the alkylcarbagermatranes containing amino acid structure were successfully applied to the Fmoc solid-phase peptide synthesis procedures(Fmoc-SPPS),and the intramolecular cross-coupling of alkyl carbagermatrane with sp2-hybridized electrophile on the resin was carried out to synthesize the bicyclic peptide structure.In recent years,our group has been working on developing a series of easily synthesized,air-stable germatranes as new synthons for Pd-catalyzed cross-coupling reactions.We have reported that various heterocyclic germatranes can be obtained by Pd-catalyzed germatranization of heterocyclic halides,but the synthesized heterocyclic germatranes are limited by the heterocyclic halides.Thus,we attempt to further explore the methods of constructing heterocyclic germatranes to extend the range of heterocyclic germatranes.In the chapter 3,we have developed a method to prepare alkynyl germatranes,then synthesized isoquinolone and isoquinoline-derivated germatranes via Rh(Ⅲ)-catalyzed C-H activation and annulation with alkynyl germatranes for the first time.Pd-catalyzed cross-coupling reactions of these stable heterocyclic germatranes have provided an effective method for further modification of specific sites of heterocycles.