Ortho-lithiation-intramolecular Nucleophilic Addition Cascade For The Synthesis Of Pyrrolo[b]sultams

As an important class of heterocyclic compounds,sultam derivatives have a wide range of applications in the fields of medicinal chemistry,organic chemistry and agricultural chemistry.These compounds exhibit important activities,such as antitumor,anti-bacterial,anti-inflammatory and inhibitory effects on enzymes,including COX-2,HIV integrase,Calpain Ⅰ and MMP-2.They can be used as protecting group,chiral auxiliary and directed metalation group(DMG)in organic chemistry.Due to their promising biological activity and wide range of uses,people have developed many synthetic methods toward the synthesis of sultams,such as metal-catalyzed C-H activation,cascade cyclization,cycloaddition,electrocyclization and multi-component reactions.In response to diversified structural requirements,many unique strategies or concise methods are still needed to synthesize sultam derivatives.In this thesis,we have developed a method for synthesizing pyrrolo[b]sultam derivatives via ortho-lithiation-intramolecular nucleophilic addition.2-Acyl-Narylsulfonylpyrrole/imidazole,N-benzenesulfonylpyrrole-2-acrylate,2benzenesulfonyl-3-benzoylpyridine,2-benzoyl-N-arylphosphonopyrrole,Northocarboxylate benzenesulfonylpyrrole/indole can react in the presence of LDA to provide target molecules in moderate to good isolated yields.Altogether,21 compounds have been synthesized.Further transformation of the products to other fused heterocyclic compounds via elimination and Diels-Alder reactions have also been described.