Transition-metal-free approaches towards synthesis of nitrogen-containing molecules

• Main Author: Zhang, Feng-Lian
• Other Authors: Chiba Shunsuke
• Format: Theses and Dissertations
• Language: English
• Published: 2015
• Subjects: DRNTU::Science::Chemistry::Organic chemistry::Heterocyclic compounds; DRNTU::Science::Chemistry::Organic chemistry::Organic synthesis
• Online Access: http://hdl.handle.net/10356/65742
• Institution: Nanyang Technological University

Nitrogen-containing molecules are omnipresent in biologically active natural products, pharmaceutical drugs and functional materials. To date, numerous transition-metal-catalyzed reactions have been investigated and applied towards synthesis of nitrogen-containing molecules. On the other hand, development of efficient supply for valuable nitrogen-containing molecules by transition-metal-free approaches is becoming more and more desirable considering the recent environmental sustainability issues as well as strict international standards about the level of transition-metal contamination in the drug ingredients. The author has developed new synthetic methods of azaheterocycles and amides operated under transition-metal-free manners during the PhD study and the detailed results will be described in this thesis. Part I of this thesis describes molecular oxygen-induced radical transformations for synthesis of azaheterocycles. Molecular oxygen (O2), as a triplet diradical in its ground state, has the ability to trigger cleavage of X-H (X = C, O) bonds through single-electron-oxidation or hydrogen abstraction pathways. It was found that amidoximes bearing relatively low BDEs of O-H bonds (80-90 kcal/mol) could generate iminoxyl radicals by O2-triggered O-H bond cleavage. The resulting iminoxyl radical underwent 1,5-H radical shift to form the corresponding C-radical, that was further transformed to 4,5-dihydro-1,2,4-oxadiazole. This 4,5-dihydro-1,2,4-oxadiazole was further oxidized to 1,2,4-oxadiazole or converted into quinazolinone through oxidative skeletal rearrangement (Scheme 1). These results are summarized in Chapter 2.