Asymmetric piperidine synthesis
It has been demonstrated that bakers' yeast reduction of 1-tert-butyl-2-methyl 3-oxo-piperidine-1,2-dicarboxylate gives (2R, 3S), 1-tert-butyl-2-methyl 3-hydroxy-piperidine-1,2-dicarboxylate in 80% chemical yield with >99% d.e. and >97% e.e. Also bakers' yeast reduction of 1-tert-but...
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| Format: | Thesis (University of Nottingham only) |
| Language: | English |
| Published: |
1995
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| Online Access: | https://eprints.nottingham.ac.uk/13293/ |
| _version_ | 1848791698466930688 |
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| author | Lewis, Neil |
| author_facet | Lewis, Neil |
| author_sort | Lewis, Neil |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | It has been demonstrated that bakers' yeast reduction of 1-tert-butyl-2-methyl 3-oxo-piperidine-1,2-dicarboxylate gives (2R, 3S), 1-tert-butyl-2-methyl 3-hydroxy-piperidine-1,2-dicarboxylate in 80% chemical yield with >99% d.e. and >97% e.e. Also bakers' yeast reduction of 1-tert-butyl-3-ethyl 4-oxo-piperidine-1,3-dicarboxylate gives (3R, 4S), 1-tert-butyl-3-ethyl4-hydroxy-piperidine-1,3-dicarboxylate in 74% chemical yield with >99% d.e. and >93% e.e. The optical purity and absolute configurations of the hydroxy-ester derivatives were determined by conversion into the corresponding chiral bis-tosylate derivatives of 2- and 3-piperidinemethanol respectively.
It has also been shown that bakers' yeast reduction of 1-tert-butyl-4-methyl 3-oxo-piperidine-1,4-dicarboxylate gives (3R, 4R)-1-tert-butyl-4-methyl 3-hydroxypiperidine-dicarboxylate in 81% chemical yield with >99% d.e. and 87% e.e. The optical purity and absolute configuration of the hydroxy-ester derivative were determined by utilisation of the compound in the total synthesis of (R)-3-quinuclidinol via chain elongation at C-4 of the piperidine followed by cyclisation to produce the bicyclic structure.
Further work is reported on the diastereoselective synthesis of polyhydroxylated indolizidine alkaloids. 1-Acetoxy-2-hydroxy-3-(hydroxymethyl)-indolizidine has been synthesised as a single diastereomer from 2-piperidinemethanol via attack of an amine onto an epoxide functionality thus producing the bicyclic system. |
| first_indexed | 2025-11-14T18:32:39Z |
| format | Thesis (University of Nottingham only) |
| id | nottingham-13293 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-14T18:32:39Z |
| publishDate | 1995 |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-132932025-02-28T11:24:18Z https://eprints.nottingham.ac.uk/13293/ Asymmetric piperidine synthesis Lewis, Neil It has been demonstrated that bakers' yeast reduction of 1-tert-butyl-2-methyl 3-oxo-piperidine-1,2-dicarboxylate gives (2R, 3S), 1-tert-butyl-2-methyl 3-hydroxy-piperidine-1,2-dicarboxylate in 80% chemical yield with >99% d.e. and >97% e.e. Also bakers' yeast reduction of 1-tert-butyl-3-ethyl 4-oxo-piperidine-1,3-dicarboxylate gives (3R, 4S), 1-tert-butyl-3-ethyl4-hydroxy-piperidine-1,3-dicarboxylate in 74% chemical yield with >99% d.e. and >93% e.e. The optical purity and absolute configurations of the hydroxy-ester derivatives were determined by conversion into the corresponding chiral bis-tosylate derivatives of 2- and 3-piperidinemethanol respectively. It has also been shown that bakers' yeast reduction of 1-tert-butyl-4-methyl 3-oxo-piperidine-1,4-dicarboxylate gives (3R, 4R)-1-tert-butyl-4-methyl 3-hydroxypiperidine-dicarboxylate in 81% chemical yield with >99% d.e. and 87% e.e. The optical purity and absolute configuration of the hydroxy-ester derivative were determined by utilisation of the compound in the total synthesis of (R)-3-quinuclidinol via chain elongation at C-4 of the piperidine followed by cyclisation to produce the bicyclic structure. Further work is reported on the diastereoselective synthesis of polyhydroxylated indolizidine alkaloids. 1-Acetoxy-2-hydroxy-3-(hydroxymethyl)-indolizidine has been synthesised as a single diastereomer from 2-piperidinemethanol via attack of an amine onto an epoxide functionality thus producing the bicyclic system. 1995 Thesis (University of Nottingham only) NonPeerReviewed application/pdf en arr https://eprints.nottingham.ac.uk/13293/1/283603.pdf Lewis, Neil (1995) Asymmetric piperidine synthesis. PhD thesis, University of Nottingham. |
| spellingShingle | Lewis, Neil Asymmetric piperidine synthesis |
| title | Asymmetric piperidine synthesis |
| title_full | Asymmetric piperidine synthesis |
| title_fullStr | Asymmetric piperidine synthesis |
| title_full_unstemmed | Asymmetric piperidine synthesis |
| title_short | Asymmetric piperidine synthesis |
| title_sort | asymmetric piperidine synthesis |
| url | https://eprints.nottingham.ac.uk/13293/ |