Abstract
We report a concise, enantioselective synthesis of the yohimbine alkaloids (-)-rauwolscine and (-)-alloyohimbane. The key transformation involves a highly enantio- and diastereoselective NHC-catalyzed dimerization and an amidation/N-acyliminium ion cyclization sequence to furnish four of the five requisite rings and three of the five stereocenters in two operations. This route also provides efficient access to all four diastereomeric arrangements of the core stereotriad of the yohimbine alkaloids from a common intermediate. This platform approach in combination with the ability to access both enantiomers from the carbene-catalyzed reaction is a powerful strategy that can produce a wide range of complex alkaloids and related structures for future biomedical investigations.
Original language | English (US) |
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Pages (from-to) | 2187-2192 |
Number of pages | 6 |
Journal | Journal of the American Chemical Society |
Volume | 142 |
Issue number | 5 |
DOIs | |
State | Published - Feb 5 2020 |
Funding
Financial support from the National Institutes of Health and Northwestern University is acknowledged (NIGMS R01 GM073072 and GM131431). The authors thank Keegan Fitzpatrick (Northwestern) for X-ray crystallographic analysis of 11 and 2 and Allison Devitt (Northwestern) for assistance with NMR characterization of 20 .
ASJC Scopus subject areas
- General Chemistry
- Biochemistry
- Catalysis
- Colloid and Surface Chemistry
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CCDC 1949992: Experimental Crystal Structure Determination
Miller, E. R. (Contributor), Hovey, M. T. (Contributor) & Scheidt, K. A. (Contributor), Cambridge Crystallographic Data Centre, 2020
DOI: 10.5517/ccdc.csd.cc23g3zp, http://www.ccdc.cam.ac.uk/services/structure_request?id=doi:10.5517/ccdc.csd.cc23g3zp&sid=DataCite
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CCDC 1949990: Experimental Crystal Structure Determination
Miller, E. R. (Contributor), Hovey, M. T. (Contributor) & Scheidt, K. A. (Contributor), Cambridge Crystallographic Data Centre, 2020
DOI: 10.5517/ccdc.csd.cc23g3xm, http://www.ccdc.cam.ac.uk/services/structure_request?id=doi:10.5517/ccdc.csd.cc23g3xm&sid=DataCite
Dataset