N-hetereocyclic carbenes-catalyzed desymmetrization and rapid access to spirocylic molecules

• Main Author: Zhuo, Shitian
• Other Authors: Chi Robin Yonggui
• Format: Theses and Dissertations
• Language: English
• Published: 2019
• Subjects: DRNTU::Science::Chemistry::Organic chemistry::Organic analysis
• Online Access: https://hdl.handle.net/10356/103675; http://hdl.handle.net/10220/47436
• Institution: Nanyang Technological University

This thesis focuses on enantioselective desymmetrization reactions enabled by N-heterocyclic carbenes (NHCs) organocatalysts. It contains four parts: Chapter 1 gives brief introductions to the history and development of NHCs organocatalysts classified by active intermediates within this field. Representative examples are summarized and reviewed as well in this part. Chapter 2 describes an NHC-thiourea co-catalysis of optical pure spirocylic skeletons via Stetter-aldol tandem reaction. Desymmetrization of a remote chiral center of the product was constructed successfully with three chiral centers, which included two remote chiral centers from the NHC catalyst reaction site. The desymmetrized products hold potential to serve as the building blocks in bioactive molecules and the chiral auxiliary, which further increases the utility of this reaction. Chapter 3 is about NHC organocatalytic strategy for the enantioselective formal [4+2] construction of multisubstituted phenols, which represents the first intermolecular cycloaddtion arene construction method. This method employs easily accessible enals and diketones to construct phenol framework with excellent regioselectivity, and simultaneously install a remote all-carbon quaternary chiral center with good enantioselectivity via desymmetrization. Chapter 4 introduces an enantioselective approach to conformationally constrained carbocyclic β-amino acids via amine-catalyzed addition of unsaturated imine gammacarbon to enal. Various imines and enal are well tolerated with excellent diastereoselectivity and enantioselectivity, which possess huge potential in the conformationally constrained β-peptides synthesis.