Date of Award

5-2019

Document Type

Campus Access Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Chemistry/Organic Chemistry

First Advisor

Wei Zhang

Second Advisor

Neil Reilly

Third Advisor

Niya Sa

Abstract

Diastereomerically enriched heterocyclic compounds play a significant role in medicinal chemistry and natural products. 1,3-Dipolar cycloaddition-initiated pot, atom and step economic ( PASE) synthesis is a powerful strategy for the construction of polyheterocycles bearing multiple stereocenters. In particular, [3+2] cycloaddition, especially 1,3-dipolar cycloaddition of azomethine ylides, has been explored for PASE synthesis of biologically active heterocyclic compounds. This work focuses on the development and application of PASE synthesis through the following projects: 1) 1,3-dipolar cycloaddition-based one-pot synthesis of a 3,9-diazabicyclo[4.2.1] nonane-containing scaffold involving reduction and lactamization; 2) PASE synthesis of fused tetrahydroquinazolines through double [3+2] cycloadditions followed by [5+1] annulation; 3) Diastereoselective one-pot synthesis involving a catalyst-free click reaction for the synthesis of triazolibenzodiazepine-fused polycyclic compounds; 4) One-pot double [3+2] cycloadditions for diastereoselective synthesis of pyrrolidine-based polycyclic systems; and 5) Non-stabilized NH azomethine ylide-initiated cascade double 1,3-dipolar cycloaddition via sequential decarboxylation and α-C-H functionalization. All of these projects employ a one-pot synthesis involving initial 1,3-dipolar cycloaddition of azomethine ylides to afford pyrrolidine-based polyheterocyclic systems in good to excellent yields and diastereoselectivities. Additionally, these processes are pot, atom and step economical (PSAE), require minimal intermediate purification, involve simple operation, highly energy-efficiency and environmentally friendly making them useful green synthesis techniques.

Comments

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