A Scalable Synthesis of (R,R)‑2,6-Dimethyldihydro‑2H‑pyran-4(3H)‑one
A scalable synthesis of (R,R)-2,6-dimethyldihydro-2H-pyran-4(3H)-one is reported. Key to this strategy is the Ti(OiPr)4-catalyzed Kulinkovich cyclopropanation of silyl protected (R)-ethyl 3-hydroxybutanoate, and subsequent oxidative fragmentation of the cyclopropanol. The resulting vinyl ketone in...
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Published in | Organic process research & development Vol. 19; no. 10; pp. 1360 - 1368 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
WASHINGTON
American Chemical Society
16.10.2015
Amer Chemical Soc |
Subjects | |
Online Access | Get full text |
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Summary: | A scalable synthesis of (R,R)-2,6-dimethyldihydro-2H-pyran-4(3H)-one is reported. Key to this strategy is the Ti(OiPr)4-catalyzed Kulinkovich cyclopropanation of silyl protected (R)-ethyl 3-hydroxybutanoate, and subsequent oxidative fragmentation of the cyclopropanol. The resulting vinyl ketone intermediate was then subjected to oxidative Heck cyclization to form the enone substrate required for conjugate addition. A diastereoselective copper-catalyzed Grignard addition procedure was implemented to install the requisite methyl group, with the inclusion of 1,3-bis(diphenylphosphino)propane and trimethylsilyl chloride greatly increasing the robustness of this process. |
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ISSN: | 1083-6160 1520-586X |
DOI: | 10.1021/op500135x |