Stereocontrolled syntheses of (-)-cubebol and (-)-10-epicubebol involving intramolecular cyclopropanation of alpha-lithiated epoxides.
Formylation of (-)-menthone (11) with LDA and HCO(2)CH(2)CF(3) avoids loss of configurational integrity at the isopropyl group, giving hydroxymethylenementhone 12. Lithium 2,2,6,6-tetramethylpiperidide-induced intramolecular cyclopropanation of derived unsaturated terminal epoxide 17 (and chlorohydr...
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| Format: | Journal article |
| Language: | English |
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2010
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| _version_ | 1826297239619764224 |
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| author | Hodgson, D Salik, S Fox, D |
| author_facet | Hodgson, D Salik, S Fox, D |
| author_sort | Hodgson, D |
| collection | OXFORD |
| description | Formylation of (-)-menthone (11) with LDA and HCO(2)CH(2)CF(3) avoids loss of configurational integrity at the isopropyl group, giving hydroxymethylenementhone 12. Lithium 2,2,6,6-tetramethylpiperidide-induced intramolecular cyclopropanation of derived unsaturated terminal epoxide 17 (and chlorohydrin 16), efficiently generates a substituted tricyclo[4.4.0.0(1,5)]decan-4-ol 18, which is used in a concise synthesis of (-)-cubebol (1). In contrast, isopropyl group inversion during formylation of menthone with NaOMe and HCO(2)Et led, by a similar strategy, to syntheses of 7-epicubebol (33) and (from (+)-menthone) of naturally occurring (-)-10-epicubebol (39), confirming the original structural assignment. Computational studies support the origin of the inversion as being rate-determining formylation of cis-enolate 27 from a mixture of rapidly interconverting enolates. In the synthesis of 7-epicubebol (33), allylic tertiary C-H insertion is observed as a significant competing reaction in the intramolecular cyclopropanation of unsaturated terminal epoxide 22. |
| first_indexed | 2024-03-07T04:28:33Z |
| format | Journal article |
| id | oxford-uuid:cd818399-416c-46eb-b9ca-b0f172e2e097 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T04:28:33Z |
| publishDate | 2010 |
| record_format | dspace |
| spelling | oxford-uuid:cd818399-416c-46eb-b9ca-b0f172e2e0972022-03-27T07:29:09ZStereocontrolled syntheses of (-)-cubebol and (-)-10-epicubebol involving intramolecular cyclopropanation of alpha-lithiated epoxides.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:cd818399-416c-46eb-b9ca-b0f172e2e097EnglishSymplectic Elements at Oxford2010Hodgson, DSalik, SFox, DFormylation of (-)-menthone (11) with LDA and HCO(2)CH(2)CF(3) avoids loss of configurational integrity at the isopropyl group, giving hydroxymethylenementhone 12. Lithium 2,2,6,6-tetramethylpiperidide-induced intramolecular cyclopropanation of derived unsaturated terminal epoxide 17 (and chlorohydrin 16), efficiently generates a substituted tricyclo[4.4.0.0(1,5)]decan-4-ol 18, which is used in a concise synthesis of (-)-cubebol (1). In contrast, isopropyl group inversion during formylation of menthone with NaOMe and HCO(2)Et led, by a similar strategy, to syntheses of 7-epicubebol (33) and (from (+)-menthone) of naturally occurring (-)-10-epicubebol (39), confirming the original structural assignment. Computational studies support the origin of the inversion as being rate-determining formylation of cis-enolate 27 from a mixture of rapidly interconverting enolates. In the synthesis of 7-epicubebol (33), allylic tertiary C-H insertion is observed as a significant competing reaction in the intramolecular cyclopropanation of unsaturated terminal epoxide 22. |
| spellingShingle | Hodgson, D Salik, S Fox, D Stereocontrolled syntheses of (-)-cubebol and (-)-10-epicubebol involving intramolecular cyclopropanation of alpha-lithiated epoxides. |
| title | Stereocontrolled syntheses of (-)-cubebol and (-)-10-epicubebol involving intramolecular cyclopropanation of alpha-lithiated epoxides. |
| title_full | Stereocontrolled syntheses of (-)-cubebol and (-)-10-epicubebol involving intramolecular cyclopropanation of alpha-lithiated epoxides. |
| title_fullStr | Stereocontrolled syntheses of (-)-cubebol and (-)-10-epicubebol involving intramolecular cyclopropanation of alpha-lithiated epoxides. |
| title_full_unstemmed | Stereocontrolled syntheses of (-)-cubebol and (-)-10-epicubebol involving intramolecular cyclopropanation of alpha-lithiated epoxides. |
| title_short | Stereocontrolled syntheses of (-)-cubebol and (-)-10-epicubebol involving intramolecular cyclopropanation of alpha-lithiated epoxides. |
| title_sort | stereocontrolled syntheses of cubebol and 10 epicubebol involving intramolecular cyclopropanation of alpha lithiated epoxides |
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