The Birch reduction-alkylation coupled to the desymmetrizing Mizoroki-Heck reaction is a novel synthetic tool to form potentially bioactive phenanthridinone analogs from inexpensive and easily available starting materials. This work describes a rare example of the direct replacement of palladium for nickel in our previously reported enantioselective intramolecular Heck reaction. A Ni-catalyzed enantioselective intramolecular Mizoroki-Heck reaction has been developed to transform symmetrical 1,4- cyclohexadienes with attached aryl halides to phenanthridinone analogs containing quaternary stereocenters. Moreover, this approach provides direct access to six-member ring heterocyclic systems bearing all-carbon quaternary stereocenters, which have been much more challenging to form enantioselectively with nickel-catalyzed Heck reactions. The first part of this project describes important advances in reaction optimization enabling control of unwanted proto-dehalogenation and alkene reduction side products. The second section focuses on the development of enantioselective strategy with a newly synthesized chiral iQuinox-type bidentate ligand. In the third section, we describe efforts to explore the substrate scope and to subsequently transform the 1,3-diene Heck products into molecules with potentially greater therapeutic relevance. In the last project chapter, mechanistic investigations and a computational study of the key 1,2-migratory insertion step shed light on the catalytic cycle and the basis for the enantioselectivity. Altogether, this work presents a very attractive alternative to the palladium-catalyzed process and should facilitate the application of Ni catalysis to traditional Heck transformations.
","abstract_html":"<p>The Birch reduction-alkylation coupled to the desymmetrizing Mizoroki-Heck reaction is a novel synthetic tool to form potentially bioactive phenanthridinone analogs from inexpensive and easily available starting materials. This work describes a rare example of the direct replacement of palladium for nickel in our previously reported enantioselective intramolecular Heck reaction. A Ni-catalyzed enantioselective intramolecular Mizoroki-Heck reaction has been developed to transform symmetrical 1,4- cyclohexadienes with attached aryl halides to phenanthridinone analogs containing quaternary stereocenters. Moreover, this approach provides direct access to six-member ring heterocyclic systems bearing all-carbon quaternary stereocenters, which have been much more challenging to form enantioselectively with nickel-catalyzed Heck reactions. The first part of this project describes important advances in reaction optimization enabling control of unwanted proto-dehalogenation and alkene reduction side products. The second section focuses on the development of enantioselective strategy with a newly synthesized chiral iQuinox-type bidentate ligand. In the third section, we describe efforts to explore the substrate scope and to subsequently transform the 1,3-diene Heck products into molecules with potentially greater therapeutic relevance. In the last project chapter, mechanistic investigations and a computational study of the key 1,2-migratory insertion step shed light on the catalytic cycle and the basis for the enantioselectivity. Altogether, this work presents a very attractive alternative to the palladium-catalyzed process and should facilitate the application of Ni catalysis to traditional Heck transformations. </p>","abstract_has_math":false,"creators":["Rachii, Diana"],"institution":null,"degree_name":"Doctor of Philosophy (PhD)","degree_level":"Open Access","degree_discipline":"Chemistry","degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2024,"date_issued":"2024-01-01T08:00:00Z","date_published":"2024-01-01T08:00:00Z","updated_at":"2026-07-24T01:23:53Z","subjects":[],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://repository.brynmawr.edu/dissertations/260","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:creator","label":"Author","values":["Rachii, Diana"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"thesis:degree_discipline","label":"Discipline","values":["Chemistry"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Open Access"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy (PhD)"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://repository.brynmawr.edu/dissertations/260"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["The Birch reduction-alkylation coupled to the desymmetrizing Mizoroki-Heck reaction is a novel synthetic tool to form potentially bioactive phenanthridinone analogs from inexpensive and easily available starting materials. This work describes a rare example of the direct replacement of palladium for nickel in our previously reported enantioselective intramolecular Heck reaction. A Ni-catalyzed enantioselective intramolecular Mizoroki-Heck reaction has been developed to transform symmetrical 1,4- cyclohexadienes with attached aryl halides to phenanthridinone analogs containing quaternary stereocenters. Moreover, this approach provides direct access to six-member ring heterocyclic systems bearing all-carbon quaternary stereocenters, which have been much more challenging to form enantioselectively with nickel-catalyzed Heck reactions. The first part of this project describes important advances in reaction optimization enabling control of unwanted proto-dehalogenation and alkene reduction side products. The second section focuses on the development of enantioselective strategy with a newly synthesized chiral iQuinox-type bidentate ligand. In the third section, we describe efforts to explore the substrate scope and to subsequently transform the 1,3-diene Heck products into molecules with potentially greater therapeutic relevance. In the last project chapter, mechanistic investigations and a computational study of the key 1,2-migratory insertion step shed light on the catalytic cycle and the basis for the enantioselectivity. Altogether, this work presents a very attractive alternative to the palladium-catalyzed process and should facilitate the application of Ni catalysis to traditional Heck transformations.
"]},{"key":"dc:title","label":"Title","values":["Development of a Ni-Catalyzed Enantioselective Intramolecular Mizoroki- Heck Reaction for the Synthesis of Phenanthridinone Derivatives"]}]}],"canonical_facts":{"dc:creator":["Rachii, Diana"],"dc:description.abstract":["The Birch reduction-alkylation coupled to the desymmetrizing Mizoroki-Heck reaction is a novel synthetic tool to form potentially bioactive phenanthridinone analogs from inexpensive and easily available starting materials. This work describes a rare example of the direct replacement of palladium for nickel in our previously reported enantioselective intramolecular Heck reaction. A Ni-catalyzed enantioselective intramolecular Mizoroki-Heck reaction has been developed to transform symmetrical 1,4- cyclohexadienes with attached aryl halides to phenanthridinone analogs containing quaternary stereocenters. Moreover, this approach provides direct access to six-member ring heterocyclic systems bearing all-carbon quaternary stereocenters, which have been much more challenging to form enantioselectively with nickel-catalyzed Heck reactions. The first part of this project describes important advances in reaction optimization enabling control of unwanted proto-dehalogenation and alkene reduction side products. The second section focuses on the development of enantioselective strategy with a newly synthesized chiral iQuinox-type bidentate ligand. In the third section, we describe efforts to explore the substrate scope and to subsequently transform the 1,3-diene Heck products into molecules with potentially greater therapeutic relevance. In the last project chapter, mechanistic investigations and a computational study of the key 1,2-migratory insertion step shed light on the catalytic cycle and the basis for the enantioselectivity. Altogether, this work presents a very attractive alternative to the palladium-catalyzed process and should facilitate the application of Ni catalysis to traditional Heck transformations.
"],"dc:identifier":["https://repository.brynmawr.edu/dissertations/260"],"dc:title":["Development of a Ni-Catalyzed Enantioselective Intramolecular Mizoroki- Heck Reaction for the Synthesis of Phenanthridinone Derivatives"],"thesis:degree_discipline":["Chemistry"],"thesis:degree_level":["Open Access"],"thesis:degree_name":["Doctor of Philosophy (PhD)"]},"updated_at":"2026-07-24T01:23:53Z"}