Lewis Acid Amide Ester As Substrate For The Radical Transfer Radical Cyclization

Radical cyclization is a powerful method for the synthesis of cyclic compounds. Atom (or group) transfer radical cyclization reactions, which involve the transfer of a halogen atom (X=I, Br, or Cl) or an aryl chalcogen group (X=SePh, or TePh) from one carbon center to another with concomitant ring formation, is particularly useful since the halogen atom or chalcogen group retained in the product allows for further functionalization.In this thesis, Lewis acid-promoted phenylseleno group transfer radical cyclization of N-alkenylβ-amide esters was developed, asymmetric group transfer radical cyclization reaction induced by chiral auxiliaries was explored, the cyclization precursors with a reporter group for kinetic studies were synthesized, and the attempt toward the synthesis of a key intermediate of (±)-kainic acid was made.In the first part of the thesis, we studied phenylseleno group transfer radical cyclization reactions of N-alkenylβ-amide esters. The results showed that Lewis acids play an important role in increasing the reaction rate and yield. For allyl and homoallyl substrates, exo-mode cyclization products were obtained. For the enamine type substrate,5-endo-mode product was obtained. For the allyl substrates with the double bond inside the ring, aza-bicyclic products were obtained. The phenylseleno group retained in the products can be further functionalized. This Lewis acid promoted phenylseleno group transfer radical cyclization represents an efficient, regioselective, and stereoselective tool for the formation ofα,β-disubstituted lactams that are important core structures of many biologically interesting natural products and medicines.In the second part of the thesis, we studied asymmetric group transfer radical cyclization reactions promoted by Lewis acids. Chiral auxiliaries such as (-)-menthol, (-)-8-phenylmenthol and (+)-8-phenylneomenthol were explored. The cyclization promoted by Lewis acid gave products in 62-78% yield. HPLC analysis showed that the auxiliaries (-)-menthol and (+)-8-phenylneomenthol have no effect on asymmetric induction (<5% ee) while (-)-8-phenylmenthol has little effect on asymmetric induction (25% ee).In the third part of the thesis, several cyclization precursors with a reporter group, such as diphenylmethine, were synthesized for further kinetic studies of theα-radicals activated by dicarbonyl groups. Since the reporter group possesses characteristic UV absorption, this strategy provides a method to determine cyclization rate through detection of the reporter group generated in tandem with cyclization by femtosecond transient absorption (fs-TA) experiments.In the fourth part of the thesis, research on the synthesis of the key intermediates of (±)-kainic acid and (±)-allokainic acid was described. Kainic acid and allokainic acid are two members of the kainoid amino acids. The kainoids have attracted considerable interest because of their pronounced insecticidal, anthelmintic and principally neuroexcitatory properties. Starting from (S)-aspartic acid, we synthesized the phenylseleno cyclization precursor by four steps. The screening of reaction condition for the cyclization is underway.