Enantioselective Syntheses of Tetrahydroisoquinolines (Thiqs) Via Iridium-Catalyzed Asymmetric Hydrogenation and Progress Toward the Total Synthesis of (+)-Cyanocycline A

• Main Author: Kim, Alexia Nahyun
• Format: Dissertation
• Language: English
• Published: ProQuest Dissertations & Theses 01-01-2023
• Subjects: Biosynthesis; Condensed matter physics; Crystallography; Epidemiology; Hydrogenation; Materials science; Pandemics; Physics; Thin films
• ISBN: 9798380267809
• DOI: 10.7907/4xty-8711

Described herein are two reviews and three projects related to the asymmetric syntheses of tetrahydroisoquinoline (THIQs) alkaloids, and the progress toward the total synthesis of (+)-cyanocycline A. In Chapter 1, a review of the development of asymmetric methodologies for the preparation of enantioenriched N-heteroarenes is detailed. In Chapter 2, the development of an iridium-catalyzed enantio- and diastereoselective hydrogenation of 1,3-disubstituted isoquinolines to achieve cis-THIQs is reported. Chapter 3 describes the iridium-catalyzed asymmetric hydrogenation of 1,3-disubstituted isoquinolines that can afford trans-THIQs in a single transformation. Preliminary mechanistic insights to the iridium-catalyzed asymmetric hydrogenation method using deuterium experiments are detailed.Chapter 4 details a comprehensive review of the advances in the total syntheses of complex THIQ alkaloids from 2000 – 2020, ranging from simple benzyl THIQ natural products to complex THIQ alkaloids such as Ecteinascidin-743. In Chapter 5, efforts toward the total synthesis of (+)-cyanocycline A are described, harnessing a nonbiomimetic synthetic route through a convergent cross-coupling of two heterocyclic fragments followed by a global hydrogenation event.