New methodologies to prepare alpha-functionalized amines, especially chiral amines have been studied in this work. Specifically, we focused our work on introducing alpha-functionalization to amines through C–C forming processes. This thesis work is inspired by the vitamin B6 transamination process: forming ketimines or aldimines to increase the acidities of alpha-C–H protons of amines, thereby enabling the alpha-C–H deprotonation accessible under mild reaction conditions for further derivation. Based on this known process mechanism, we first explored the umpolung functionalization of amines through deprotonation of ketimines/aldimines, then a migratory insertion process from metal-hydrides to 2-azadienes have been further developed. Of these processes, this thesis work will specifically focus on the research exploration of three synthons: 2-azaallyl anion, 2-azaaalyl radical and 2-azadiene.
We began investigating processes to access alpha-amino anions directly through alpha-deprotonation of imines (formation of 2-azaallyl anions). The alpha-amino anion was then utilized in two further reactions: 1. enantiospecific ring-opening of aziridines to access 1,3-diamines and 2. enantioselective Pd-catalyzed allylation to obtain homoallylic amines.
Following our research of 2-azaallyl anions, we developed a metal-free cross-coupling reaction between 2-azaallyl radicals and single-electron acceptors such as 1,4-dicyanobenzene. The reaction efficiently delivered the desired two-component product at room temperature without additional catalysts. This reaction indicated the formation of radical pairs : 2-azaallyl radicals from 2-azaallyl anions and radical anions from the single-electron acceptors. We then examined a few plausible three-component coupling reactions to utilize alkene to intercept the radical pairs to prepare more complicated functionalized amines.
In the last part, we have developed 2-azadienes as platforms to access functionalized amines via alpha-amino transition metal species. Through migratory insertion of a copper hydride into 2-azadienes, we could access alpha-aminoalkyl metal species, which could be further used in reactions with various electrophiles. Two applications were examined in this chapter: 1) addition to ketones to access 1,2-amino tertiary alcohols and 2) addition to aldimines/ketimines to access 1,2-diamines.
","abstract_html":"<p>New methodologies to prepare alpha-functionalized amines, especially chiral amines have been studied in this work. Specifically, we focused our work on introducing alpha-functionalization to amines through C–C forming processes. This thesis work is inspired by the vitamin B6 transamination process: forming ketimines or aldimines to increase the acidities of alpha-C–H protons of amines, thereby enabling the alpha-C–H deprotonation accessible under mild reaction conditions for further derivation. Based on this known process mechanism, we first explored the umpolung functionalization of amines through deprotonation of ketimines/aldimines, then a migratory insertion process from metal-hydrides to 2-azadienes have been further developed. Of these processes, this thesis work will specifically focus on the research exploration of three synthons: 2-azaallyl anion, 2-azaaalyl radical and 2-azadiene. </p><p> We began investigating processes to access alpha-amino anions directly through alpha-deprotonation of imines (formation of 2-azaallyl anions). The alpha-amino anion was then utilized in two further reactions: 1. enantiospecific ring-opening of aziridines to access 1,3-diamines and 2. enantioselective Pd-catalyzed allylation to obtain homoallylic amines.</p><p> Following our research of 2-azaallyl anions, we developed a metal-free cross-coupling reaction between 2-azaallyl radicals and single-electron acceptors such as 1,4-dicyanobenzene. The reaction efficiently delivered the desired two-component product at room temperature without additional catalysts. This reaction indicated the formation of radical pairs : 2-azaallyl radicals from 2-azaallyl anions and radical anions from the single-electron acceptors. We then examined a few plausible three-component coupling reactions to utilize alkene to intercept the radical pairs to prepare more complicated functionalized amines. </p><p>In the last part, we have developed 2-azadienes as platforms to access functionalized amines via alpha-amino transition metal species. Through migratory insertion of a copper hydride into 2-azadienes, we could access alpha-aminoalkyl metal species, which could be further used in reactions with various electrophiles. Two applications were examined in this chapter: 1) addition to ketones to access 1,2-amino tertiary alcohols and 2) addition to aldimines/ketimines to access 1,2-diamines.</p>","abstract_has_math":false,"creators":["Li, Kangnan"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["Malcolmson, Steven J"],"committee_chairs":[],"committee_members":[],"year":2018,"date_issued":"2018","date_published":"2018","updated_at":"2026-07-24T02:07:03Z","subjects":["Chemistry"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/10161/18248","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Malcolmson, Steven J"]},{"key":"dc:creator","label":"Author","values":["Li, Kangnan"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2019-04-02T16:27:20Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2021-01-09T09:17:08Z"]},{"key":"dc:date.issued","label":"Date","values":["2018"]},{"key":"dc:type","label":"Dc Type","values":["Dissertation"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Chemistry"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://hdl.handle.net/10161/18248"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["New methodologies to prepare alpha-functionalized amines, especially chiral amines have been studied in this work. Specifically, we focused our work on introducing alpha-functionalization to amines through C–C forming processes. This thesis work is inspired by the vitamin B6 transamination process: forming ketimines or aldimines to increase the acidities of alpha-C–H protons of amines, thereby enabling the alpha-C–H deprotonation accessible under mild reaction conditions for further derivation. Based on this known process mechanism, we first explored the umpolung functionalization of amines through deprotonation of ketimines/aldimines, then a migratory insertion process from metal-hydrides to 2-azadienes have been further developed. Of these processes, this thesis work will specifically focus on the research exploration of three synthons: 2-azaallyl anion, 2-azaaalyl radical and 2-azadiene.
We began investigating processes to access alpha-amino anions directly through alpha-deprotonation of imines (formation of 2-azaallyl anions). The alpha-amino anion was then utilized in two further reactions: 1. enantiospecific ring-opening of aziridines to access 1,3-diamines and 2. enantioselective Pd-catalyzed allylation to obtain homoallylic amines.
Following our research of 2-azaallyl anions, we developed a metal-free cross-coupling reaction between 2-azaallyl radicals and single-electron acceptors such as 1,4-dicyanobenzene. The reaction efficiently delivered the desired two-component product at room temperature without additional catalysts. This reaction indicated the formation of radical pairs : 2-azaallyl radicals from 2-azaallyl anions and radical anions from the single-electron acceptors. We then examined a few plausible three-component coupling reactions to utilize alkene to intercept the radical pairs to prepare more complicated functionalized amines.
In the last part, we have developed 2-azadienes as platforms to access functionalized amines via alpha-amino transition metal species. Through migratory insertion of a copper hydride into 2-azadienes, we could access alpha-aminoalkyl metal species, which could be further used in reactions with various electrophiles. Two applications were examined in this chapter: 1) addition to ketones to access 1,2-amino tertiary alcohols and 2) addition to aldimines/ketimines to access 1,2-diamines.
"]},{"key":"dc:title","label":"Title","values":["New Strategies and Transformations for the alpha-Functionalization of Amines to Access Chiral Amines"]}]}],"canonical_facts":{"dc:contributor.advisor":["Malcolmson, Steven J"],"dc:creator":["Li, Kangnan"],"dc:date.accessioned":["2019-04-02T16:27:20Z"],"dc:date.available":["2021-01-09T09:17:08Z"],"dc:date.issued":["2018"],"dc:description.abstract":["New methodologies to prepare alpha-functionalized amines, especially chiral amines have been studied in this work. Specifically, we focused our work on introducing alpha-functionalization to amines through C–C forming processes. This thesis work is inspired by the vitamin B6 transamination process: forming ketimines or aldimines to increase the acidities of alpha-C–H protons of amines, thereby enabling the alpha-C–H deprotonation accessible under mild reaction conditions for further derivation. Based on this known process mechanism, we first explored the umpolung functionalization of amines through deprotonation of ketimines/aldimines, then a migratory insertion process from metal-hydrides to 2-azadienes have been further developed. Of these processes, this thesis work will specifically focus on the research exploration of three synthons: 2-azaallyl anion, 2-azaaalyl radical and 2-azadiene.
We began investigating processes to access alpha-amino anions directly through alpha-deprotonation of imines (formation of 2-azaallyl anions). The alpha-amino anion was then utilized in two further reactions: 1. enantiospecific ring-opening of aziridines to access 1,3-diamines and 2. enantioselective Pd-catalyzed allylation to obtain homoallylic amines.
Following our research of 2-azaallyl anions, we developed a metal-free cross-coupling reaction between 2-azaallyl radicals and single-electron acceptors such as 1,4-dicyanobenzene. The reaction efficiently delivered the desired two-component product at room temperature without additional catalysts. This reaction indicated the formation of radical pairs : 2-azaallyl radicals from 2-azaallyl anions and radical anions from the single-electron acceptors. We then examined a few plausible three-component coupling reactions to utilize alkene to intercept the radical pairs to prepare more complicated functionalized amines.
In the last part, we have developed 2-azadienes as platforms to access functionalized amines via alpha-amino transition metal species. Through migratory insertion of a copper hydride into 2-azadienes, we could access alpha-aminoalkyl metal species, which could be further used in reactions with various electrophiles. Two applications were examined in this chapter: 1) addition to ketones to access 1,2-amino tertiary alcohols and 2) addition to aldimines/ketimines to access 1,2-diamines.
"],"dc:identifier.uri":["https://hdl.handle.net/10161/18248"],"dc:subject":["Chemistry"],"dc:title":["New Strategies and Transformations for the alpha-Functionalization of Amines to Access Chiral Amines"],"dc:type":["Dissertation"]},"updated_at":"2026-07-24T02:07:03Z"}