2026-09-21T14:12:24Zhttps://dspace.mit.edu/server/oai/requestoai:dspace.mit.edu:1721.1/1432592022-06-16T03:34:20Zcom_1721.1_7582com_1721.1_7581col_1721.1_131022
Movassaghi, Mohammad
Flynn, Kristen M.
Massachusetts Institute of Technology. Department of Chemistry
2022-06-15T13:07:53Z
2022-06-15T13:07:53Z
2022-02
2022-03-03T18:34:58.524Z
https://hdl.handle.net/1721.1/143259
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.
Ph.D.
Massachusetts Institute of Technology
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http://rightsstatements.org/page/InC-EDU/1.0/
Directed Palladium Catalyzed Acetoxylation of Indolines and Enantioselective Total Synthesis of (–)-Voacinol and (–)-Voacandimine C
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<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>
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