{"id":{"repo_id":"mit","oai_identifier":"oai:dspace.mit.edu:1721.1/143259"},"canonical_url":"https://search.dev.ndltd.org/etd/mit/oai:dspace.mit.edu:1721.1/143259","repository":{"repo_id":"mit","name":"MIT","base_url":"https://dspace.mit.edu/oai/request"},"display":{"title":"Directed Palladium Catalyzed Acetoxylation of Indolines and Enantioselective Total Synthesis of (–)-Voacinol and (–)-Voacandimine C","abstract":"I. Directed Palladium Catalyzed Acetoxylation of Indolines. Total Synthesis of N-Benzoylcylindrocarine We describe a palladium catalyzed C7-acetoxylation of indolines with a range of amide directing groups. While a variety of substituents are tolerated on the indoline-core and the N1-acyl group, the acetoxylation is most sensitive to the C2- and C6-indoline substituents. The practicality of this indoline C7-acetoxylation is demonstrated using a cinnamamide substrate on mmol-scale. Several N1-acyl groups, including those present in natural alkaloids, guide C7-acetoxylation of indoline substrates over a competitive C5-oxidation. The application of this chemistry allowed for the first synthesis of N-benzoylcylindrocarine by late-stage C17-acetoxylation of N-benzoylfendleridine. II. Total Synthesis of (–)-Voacinol and (–)-Voacandimine C We describe the first total synthesis of complex aspidosperma alkaloids (–)-voacinol and (–)-voacandmine C via a biogenetically inspired late-stage C7-methylenation strategy. We envisioned rapid access to these natural alkaloids from a common symmetrical precursor assembled by methylenation of a D-ring oxidized variant of the related natural product (–)-deoxoapodine. Chemoselective N9-oxidation of a pentacyclic deoxoapodine precursor enabled the synthesis of the corresponding hexacyclic C8-aminonitrile. Stereocontrolled methylenation of a C8-enamine derivative of deoxoapodine, accessed by ionization of the C8-aminonitrile, afforded a symmetrical dodecacyclic bis-aminonitrile. Final-stage biogenetically inspired controlled reductive opening of the oxolanes of this dodecacyclic intermediate provided a unified approach to (–)-voacinol and (–)-voacandmine C, while direct reduction of the same intermediate afforded structurally related (–)-methylenebisdeoxoapodine.","abstract_html":"I. Directed Palladium Catalyzed Acetoxylation of Indolines. Total Synthesis of N-Benzoylcylindrocarine We describe a palladium catalyzed C7-acetoxylation of indolines with a range of amide directing groups. While a variety of substituents are tolerated on the indoline-core and the N1-acyl group, the acetoxylation is most sensitive to the C2- and C6-indoline substituents. The practicality of this indoline C7-acetoxylation is demonstrated using a cinnamamide substrate on mmol-scale. Several N1-acyl groups, including those present in natural alkaloids, guide C7-acetoxylation of indoline substrates over a competitive C5-oxidation. The application of this chemistry allowed for the first synthesis of N-benzoylcylindrocarine by late-stage C17-acetoxylation of N-benzoylfendleridine. II. Total Synthesis of (–)-Voacinol and (–)-Voacandimine C We describe the first total synthesis of complex aspidosperma alkaloids (–)-voacinol and (–)-voacandmine C via a biogenetically inspired late-stage C7-methylenation strategy. We envisioned rapid access to these natural alkaloids from a common symmetrical precursor assembled by methylenation of a D-ring oxidized variant of the related natural product (–)-deoxoapodine. Chemoselective N9-oxidation of a pentacyclic deoxoapodine precursor enabled the synthesis of the corresponding hexacyclic C8-aminonitrile. Stereocontrolled methylenation of a C8-enamine derivative of deoxoapodine, accessed by ionization of the C8-aminonitrile, afforded a symmetrical dodecacyclic bis-aminonitrile. Final-stage biogenetically inspired controlled reductive opening of the oxolanes of this dodecacyclic intermediate provided a unified approach to (–)-voacinol and (–)-voacandmine C, while direct reduction of the same intermediate afforded structurally related (–)-methylenebisdeoxoapodine.","abstract_has_math":false,"creators":["Flynn, Kristen M."],"institution":"Massachusetts Institute of Technology","degree_name":"Doctoral","degree_level":null,"degree_discipline":null,"degree_department":"Massachusetts Institute of Technology. Department of Chemistry","school":null,"contributors":[],"advisors":["Movassaghi, Mohammad"],"committee_chairs":[],"committee_members":[],"year":2022,"date_issued":"2022-02","date_published":"2022-02","updated_at":"2026-07-22T22:21:29Z","subjects":[],"languages":[],"rights":["In Copyright - Educational Use Permitted","Copyright MIT"],"rights_urls":["http://rightsstatements.org/page/InC-EDU/1.0/"],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/1721.1/143259","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Movassaghi, Mohammad"]},{"key":"dc:contributor.department","label":"Department","values":["Massachusetts Institute of Technology. Department of Chemistry"]},{"key":"dc:creator","label":"Author","values":["Flynn, Kristen M."]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2022-06-15T13:07:53Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2022-06-15T13:07:53Z"]},{"key":"dc:date.issued","label":"Date","values":["2022-02"]},{"key":"dc:publisher","label":"Institution","values":["Massachusetts Institute of Technology"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctoral","Doctor of Philosophy"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:rights","label":"Dc Rights","values":["In Copyright - Educational Use Permitted","Copyright MIT"]},{"key":"dc:rights.uri","label":"Rights URI","values":["http://rightsstatements.org/page/InC-EDU/1.0/"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://hdl.handle.net/1721.1/143259"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["I. Directed Palladium Catalyzed Acetoxylation of Indolines. Total Synthesis of N-Benzoylcylindrocarine We describe a palladium catalyzed C7-acetoxylation of indolines with a range of amide directing groups. While a variety of substituents are tolerated on the indoline-core and the N1-acyl group, the acetoxylation is most sensitive to the C2- and C6-indoline substituents. The practicality of this indoline C7-acetoxylation is demonstrated using a cinnamamide substrate on mmol-scale. Several N1-acyl groups, including those present in natural alkaloids, guide C7-acetoxylation of indoline substrates over a competitive C5-oxidation. The application of this chemistry allowed for the first synthesis of N-benzoylcylindrocarine by late-stage C17-acetoxylation of N-benzoylfendleridine. II. Total Synthesis of (–)-Voacinol and (–)-Voacandimine C We describe the first total synthesis of complex aspidosperma alkaloids (–)-voacinol and (–)-voacandmine C via a biogenetically inspired late-stage C7-methylenation strategy. We envisioned rapid access to these natural alkaloids from a common symmetrical precursor assembled by methylenation of a D-ring oxidized variant of the related natural product (–)-deoxoapodine. Chemoselective N9-oxidation of a pentacyclic deoxoapodine precursor enabled the synthesis of the corresponding hexacyclic C8-aminonitrile. Stereocontrolled methylenation of a C8-enamine derivative of deoxoapodine, accessed by ionization of the C8-aminonitrile, afforded a symmetrical dodecacyclic bis-aminonitrile. Final-stage biogenetically inspired controlled reductive opening of the oxolanes of this dodecacyclic intermediate provided a unified approach to (–)-voacinol and (–)-voacandmine C, while direct reduction of the same intermediate afforded structurally related (–)-methylenebisdeoxoapodine."]},{"key":"dc:description.degree","label":"Dc Description Degree","values":["Ph.D."]},{"key":"dc:title","label":"Title","values":["Directed Palladium Catalyzed Acetoxylation of Indolines and Enantioselective Total Synthesis of (–)-Voacinol and (–)-Voacandimine C"]}]}],"canonical_facts":{"dc:contributor.advisor":["Movassaghi, Mohammad"],"dc:contributor.department":["Massachusetts Institute of Technology. Department of Chemistry"],"dc:creator":["Flynn, Kristen M."],"dc:date.accessioned":["2022-06-15T13:07:53Z"],"dc:date.available":["2022-06-15T13:07:53Z"],"dc:date.issued":["2022-02"],"dc:description.abstract":["I. Directed Palladium Catalyzed Acetoxylation of Indolines. Total Synthesis of N-Benzoylcylindrocarine We describe a palladium catalyzed C7-acetoxylation of indolines with a range of amide directing groups. While a variety of substituents are tolerated on the indoline-core and the N1-acyl group, the acetoxylation is most sensitive to the C2- and C6-indoline substituents. The practicality of this indoline C7-acetoxylation is demonstrated using a cinnamamide substrate on mmol-scale. Several N1-acyl groups, including those present in natural alkaloids, guide C7-acetoxylation of indoline substrates over a competitive C5-oxidation. The application of this chemistry allowed for the first synthesis of N-benzoylcylindrocarine by late-stage C17-acetoxylation of N-benzoylfendleridine. II. Total Synthesis of (–)-Voacinol and (–)-Voacandimine C We describe the first total synthesis of complex aspidosperma alkaloids (–)-voacinol and (–)-voacandmine C via a biogenetically inspired late-stage C7-methylenation strategy. We envisioned rapid access to these natural alkaloids from a common symmetrical precursor assembled by methylenation of a D-ring oxidized variant of the related natural product (–)-deoxoapodine. Chemoselective N9-oxidation of a pentacyclic deoxoapodine precursor enabled the synthesis of the corresponding hexacyclic C8-aminonitrile. Stereocontrolled methylenation of a C8-enamine derivative of deoxoapodine, accessed by ionization of the C8-aminonitrile, afforded a symmetrical dodecacyclic bis-aminonitrile. Final-stage biogenetically inspired controlled reductive opening of the oxolanes of this dodecacyclic intermediate provided a unified approach to (–)-voacinol and (–)-voacandmine C, while direct reduction of the same intermediate afforded structurally related (–)-methylenebisdeoxoapodine."],"dc:description.degree":["Ph.D."],"dc:identifier.uri":["https://hdl.handle.net/1721.1/143259"],"dc:publisher":["Massachusetts Institute of Technology"],"dc:rights":["In Copyright - Educational Use Permitted","Copyright MIT"],"dc:rights.uri":["http://rightsstatements.org/page/InC-EDU/1.0/"],"dc:title":["Directed Palladium Catalyzed Acetoxylation of Indolines and Enantioselective Total Synthesis of (–)-Voacinol and (–)-Voacandimine C"],"dc:type":["Thesis"],"thesis:degree_name":["Doctoral","Doctor of Philosophy"]},"updated_at":"2026-07-22T22:21:29Z"}