Stereoselective functionalization of azetidines

Shahbaz, Muhammad (2025): Stereoselective functionalization of azetidines. Dissertation, LMU München: Faculty of Chemistry and Pharmacy

Abstract

The synthesis of functionalized azetidine molecules has been and will continue to be crucial in advancing organic chemistry, as azetidine frameworks are among the most valuable structural motifs present in natural products and commercialized drugs. Due to this, the area of synthetic organic chemistry is continuously striving to develop innovative techniques that surpass previous generations in terms of cost and sustainability. The fundamental purpose of this thesis is to meet the ongoing demand for the creation of supplementary techniques and alternatives. Therefore, this work presents the diastereoselective approach for the synthesis of the functionalized azetidine molecules under several conditions. Initially, a range of techniques were employed to develop effective and widely recognized procedures for synthesizing fundamental 3-arylated azetidine compounds using various Grignard reagents. At last, established various approaches to achieve α-lithiation followed by electrophile trapping of 3-arylated N-protected azetidine and further applications to peptide formation. Also, selective 3-arylated azetidine intermediates can be formed through strain-release approach by adding nucleophilic organometallic species to in situ produced azabicyclobutanes. For the N-arylation of the resultant azetidines, single pot methods were further developed using Buchwald-Hartwig couplings or SNAr reactions.

• Item Type: Theses (Dissertation, LMU Munich)
• Keywords: Organic synthesis, organometallic chemistry, and azetidines functionalization.
• Subjects: 500 Natural sciences and mathematics; 500 Natural sciences and mathematics > 540 Chemistry and allied sciences
• Faculties: Faculty of Chemistry and Pharmacy
• Language: English
• Date of oral examination: 6. May 2025
• 1. Referee: Didier, Dorian
• Signature of the printed copy: 0001/UMC 31207