New Methodologies in Organic Chemistry: Applications to the Synthesis of ?-Amino Acids and Natural Products

Sammanfattning: This thesis deals with the development and application of new synthetic methodology in organic chemistry.The first part describes the development of a new protocol for the synthesis of 3-pyrrolines by means of a microwave-assisted ring-expansion reaction of 2-vinylaziridines. In addition, this methodology is implemented as a key-step in a formal total synthesis of the antibiotic (-)-anisomycin.In the second part, a new methodology for the synthesis of arylglycines from Weinreb amides is described. In this procedure, a Grignard reagent is added to the iminium ion formed from the Weinreb amide upon treatment with a base. When a chiral amide is used, the nucleophilic addition proceeds with high diastereoselectivity.Finally, an easy and straightforward synthesis of ?-amino amides via a base-mediated rearrangement of modified Weinreb amides into N,O-acetals is presented. Subsequent arylation, alkylation, alkenylation or alkynylation of this intermediate affords the corresponding ?-amino amides in excellent yields. Furthermore, a more generalized protocol for the ?-arylation of Weinreb amides lacking an ?-amino moiety is also discussed.