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

• Main Author: Hirner, Sebastian
• Format: Doctoral Thesis
• Language: English
• Published: KTH, Organisk kemi 2009
• Subjects: Organic synthesis; 2-Vinylaziridines; 3-Pyrrolines; Ringexpansion; Rearrangement; Anisomycin; Total synthesis; α-Amino acids; Arylglycines; Weinreb amides; α-Arylation; Grignard reagents; Umpolung; Organic chemistry; Organisk kemi
• Online Access: http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-11112; http://nbn-resolving.de/urn:isbn:978-91-7415-404-7

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 α-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 α-amino amides in excellent yields. Furthermore, a more generalized protocol for the α-arylation of Weinreb amides lacking an α-amino moiety is also discussed. === QC 20100719