Cation-controlled enantioselective and diastereoselective synthesis of indolines: an autoinductive phase-transfer initiated 5-endo-trig process
A catalytic enantioselective approach to the synthesis of indolines bearing two asymmetric centers, one of which is all-carbon and quaternary, is described. This reaction proceeds with high levels of diastereoselectivity (>20:1) and high levels of enantioselectivity (up to 99.5:0.5 er) in t...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | eng |
| Published: |
American Chemical Society
2015
|
| _version_ | 1797079346149588992 |
|---|---|
| author | Sharma, K Wolstenhulme, J Painter, P Yeo, D Grande-Carmona, F Johnston, C Tantillo, D Smith, M |
| author_facet | Sharma, K Wolstenhulme, J Painter, P Yeo, D Grande-Carmona, F Johnston, C Tantillo, D Smith, M |
| author_sort | Sharma, K |
| collection | OXFORD |
| description | A catalytic enantioselective approach to the synthesis of indolines bearing two asymmetric centers, one of which is all-carbon and quaternary, is described. This reaction proceeds with high levels of diastereoselectivity (>20:1) and high levels of enantioselectivity (up to 99.5:0.5 er) in the presence of CsOH·H2O and a quinine-derived ammonium salt. The reaction most likely proceeds via a delocalized 2-aza-pentadienyl anion that cyclizes either by a suprafacial electrocyclic mechanism, or through a kinetically controlled 5-endo-trig Mannich process. Density functional theory calculations are used to probe these two mechanistic pathways and lead to the conclusion that a nonpericyclic mechanism is most probable. The base-catalyzed interconversion of diastereoisomeric indolines in the presence of certain quaternary ammonium catalysts is observed; this may be rationalized as a cycloreversion-cyclization process. Mechanistic investigations have demonstrated that the reaction is initiated via a Mąkosza-like interfacial process, and kinetic analysis has shown that the reaction possesses a significant induction period consistent with autoinduction. A zwitterionic quinine-derived entity generated by deprotonation of an ammonium salt with the anionic reaction product is identified as a key catalytic species and the role that protonation plays in the enantioselective process outlined. We also propose that the reaction subsequently occurs entirely within the organic phase. Consequently, the reaction may be better described as a phase-transfer-initiated rather than a phase-transfer-catalyzed process; this observation may have implications for mechanistic pathways followed by other phase-transfer-mediated reactions. |
| first_indexed | 2024-03-07T00:44:32Z |
| format | Journal article |
| id | oxford-uuid:842a5d0b-e644-4805-ba0c-68a1f5006a23 |
| institution | University of Oxford |
| language | eng |
| last_indexed | 2024-03-07T00:44:32Z |
| publishDate | 2015 |
| publisher | American Chemical Society |
| record_format | dspace |
| spelling | oxford-uuid:842a5d0b-e644-4805-ba0c-68a1f5006a232022-03-26T21:49:22ZCation-controlled enantioselective and diastereoselective synthesis of indolines: an autoinductive phase-transfer initiated 5-endo-trig processJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:842a5d0b-e644-4805-ba0c-68a1f5006a23engSymplectic Elements at OxfordAmerican Chemical Society2015Sharma, KWolstenhulme, JPainter, PYeo, DGrande-Carmona, FJohnston, CTantillo, DSmith, M A catalytic enantioselective approach to the synthesis of indolines bearing two asymmetric centers, one of which is all-carbon and quaternary, is described. This reaction proceeds with high levels of diastereoselectivity (>20:1) and high levels of enantioselectivity (up to 99.5:0.5 er) in the presence of CsOH·H2O and a quinine-derived ammonium salt. The reaction most likely proceeds via a delocalized 2-aza-pentadienyl anion that cyclizes either by a suprafacial electrocyclic mechanism, or through a kinetically controlled 5-endo-trig Mannich process. Density functional theory calculations are used to probe these two mechanistic pathways and lead to the conclusion that a nonpericyclic mechanism is most probable. The base-catalyzed interconversion of diastereoisomeric indolines in the presence of certain quaternary ammonium catalysts is observed; this may be rationalized as a cycloreversion-cyclization process. Mechanistic investigations have demonstrated that the reaction is initiated via a Mąkosza-like interfacial process, and kinetic analysis has shown that the reaction possesses a significant induction period consistent with autoinduction. A zwitterionic quinine-derived entity generated by deprotonation of an ammonium salt with the anionic reaction product is identified as a key catalytic species and the role that protonation plays in the enantioselective process outlined. We also propose that the reaction subsequently occurs entirely within the organic phase. Consequently, the reaction may be better described as a phase-transfer-initiated rather than a phase-transfer-catalyzed process; this observation may have implications for mechanistic pathways followed by other phase-transfer-mediated reactions. |
| spellingShingle | Sharma, K Wolstenhulme, J Painter, P Yeo, D Grande-Carmona, F Johnston, C Tantillo, D Smith, M Cation-controlled enantioselective and diastereoselective synthesis of indolines: an autoinductive phase-transfer initiated 5-endo-trig process |
| title | Cation-controlled enantioselective and diastereoselective synthesis of indolines: an autoinductive phase-transfer initiated 5-endo-trig process |
| title_full | Cation-controlled enantioselective and diastereoselective synthesis of indolines: an autoinductive phase-transfer initiated 5-endo-trig process |
| title_fullStr | Cation-controlled enantioselective and diastereoselective synthesis of indolines: an autoinductive phase-transfer initiated 5-endo-trig process |
| title_full_unstemmed | Cation-controlled enantioselective and diastereoselective synthesis of indolines: an autoinductive phase-transfer initiated 5-endo-trig process |
| title_short | Cation-controlled enantioselective and diastereoselective synthesis of indolines: an autoinductive phase-transfer initiated 5-endo-trig process |
| title_sort | cation controlled enantioselective and diastereoselective synthesis of indolines an autoinductive phase transfer initiated 5 endo trig process |
| work_keys_str_mv | AT sharmak cationcontrolledenantioselectiveanddiastereoselectivesynthesisofindolinesanautoinductivephasetransferinitiated5endotrigprocess AT wolstenhulmej cationcontrolledenantioselectiveanddiastereoselectivesynthesisofindolinesanautoinductivephasetransferinitiated5endotrigprocess AT painterp cationcontrolledenantioselectiveanddiastereoselectivesynthesisofindolinesanautoinductivephasetransferinitiated5endotrigprocess AT yeod cationcontrolledenantioselectiveanddiastereoselectivesynthesisofindolinesanautoinductivephasetransferinitiated5endotrigprocess AT grandecarmonaf cationcontrolledenantioselectiveanddiastereoselectivesynthesisofindolinesanautoinductivephasetransferinitiated5endotrigprocess AT johnstonc cationcontrolledenantioselectiveanddiastereoselectivesynthesisofindolinesanautoinductivephasetransferinitiated5endotrigprocess AT tantillod cationcontrolledenantioselectiveanddiastereoselectivesynthesisofindolinesanautoinductivephasetransferinitiated5endotrigprocess AT smithm cationcontrolledenantioselectiveanddiastereoselectivesynthesisofindolinesanautoinductivephasetransferinitiated5endotrigprocess |