The asymmetric syntheses of pyrrolizidines, indolizidines and quinolizidines via two sequential tandem ring-closure/N-debenzylation processes.
Concise asymmetric syntheses of (-)-lupinine, (+)-isoretronecanol, (+)-5-epi-tashiromine and (R,R)-1-(hydroxymethyl)octahydroindolizine (the azabicyclic core within stellettamides A-C) have been achieved in 8 steps or fewer from commercially available starting materials. The key steps in these synth...
| Main Authors: | , , , , , , |
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| Format: | Journal article |
| Language: | English |
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Royal Society of Chemistry
2014
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| _version_ | 1797097347097821184 |
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| author | Davies, S Fletcher, A Foster, E Houlsby, I Roberts, P Schofield, T Thomson, J |
| author_facet | Davies, S Fletcher, A Foster, E Houlsby, I Roberts, P Schofield, T Thomson, J |
| author_sort | Davies, S |
| collection | OXFORD |
| description | Concise asymmetric syntheses of (-)-lupinine, (+)-isoretronecanol, (+)-5-epi-tashiromine and (R,R)-1-(hydroxymethyl)octahydroindolizine (the azabicyclic core within stellettamides A-C) have been achieved in 8 steps or fewer from commercially available starting materials. The key steps in these syntheses involved the preparation of enantiopure β-amino esters, upon conjugate addition of lithium (R)-N-(p-methoxybenzyl)-N-(α-methyl-p-methoxybenzyl)amide to either ζ-chloro or ζ-hydroxy substituted tert-butyl (E)-hept-2-enoate, or ε-chloro or ε-hydroxy substituted tert-butyl (E)-hex-2-enoate. Activation of the ω-substituent as a leaving group led to SN2-type ring-closure, which occurred with concomitant N-debenzylation via an E1-type deprotection step, to give the corresponding pyrrolidine or piperidine in good yield. Subsequent alkylation of these enantiopure azacycles, followed by a second ring-closure/concomitant N-debenzylation step formed the pyrrolizidine, indolizidine or quinolizidine motif, and reduction with LiAlH4 gave the target compounds in diastereoisomerically and enantiomerically pure form. |
| first_indexed | 2024-03-07T04:54:14Z |
| format | Journal article |
| id | oxford-uuid:d60cdd79-02de-4391-96dd-6b47cfe7b888 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T04:54:14Z |
| publishDate | 2014 |
| publisher | Royal Society of Chemistry |
| record_format | dspace |
| spelling | oxford-uuid:d60cdd79-02de-4391-96dd-6b47cfe7b8882022-03-27T08:30:25ZThe asymmetric syntheses of pyrrolizidines, indolizidines and quinolizidines via two sequential tandem ring-closure/N-debenzylation processes.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:d60cdd79-02de-4391-96dd-6b47cfe7b888EnglishSymplectic Elements at OxfordRoyal Society of Chemistry2014Davies, SFletcher, AFoster, EHoulsby, IRoberts, PSchofield, TThomson, JConcise asymmetric syntheses of (-)-lupinine, (+)-isoretronecanol, (+)-5-epi-tashiromine and (R,R)-1-(hydroxymethyl)octahydroindolizine (the azabicyclic core within stellettamides A-C) have been achieved in 8 steps or fewer from commercially available starting materials. The key steps in these syntheses involved the preparation of enantiopure β-amino esters, upon conjugate addition of lithium (R)-N-(p-methoxybenzyl)-N-(α-methyl-p-methoxybenzyl)amide to either ζ-chloro or ζ-hydroxy substituted tert-butyl (E)-hept-2-enoate, or ε-chloro or ε-hydroxy substituted tert-butyl (E)-hex-2-enoate. Activation of the ω-substituent as a leaving group led to SN2-type ring-closure, which occurred with concomitant N-debenzylation via an E1-type deprotection step, to give the corresponding pyrrolidine or piperidine in good yield. Subsequent alkylation of these enantiopure azacycles, followed by a second ring-closure/concomitant N-debenzylation step formed the pyrrolizidine, indolizidine or quinolizidine motif, and reduction with LiAlH4 gave the target compounds in diastereoisomerically and enantiomerically pure form. |
| spellingShingle | Davies, S Fletcher, A Foster, E Houlsby, I Roberts, P Schofield, T Thomson, J The asymmetric syntheses of pyrrolizidines, indolizidines and quinolizidines via two sequential tandem ring-closure/N-debenzylation processes. |
| title | The asymmetric syntheses of pyrrolizidines, indolizidines and quinolizidines via two sequential tandem ring-closure/N-debenzylation processes. |
| title_full | The asymmetric syntheses of pyrrolizidines, indolizidines and quinolizidines via two sequential tandem ring-closure/N-debenzylation processes. |
| title_fullStr | The asymmetric syntheses of pyrrolizidines, indolizidines and quinolizidines via two sequential tandem ring-closure/N-debenzylation processes. |
| title_full_unstemmed | The asymmetric syntheses of pyrrolizidines, indolizidines and quinolizidines via two sequential tandem ring-closure/N-debenzylation processes. |
| title_short | The asymmetric syntheses of pyrrolizidines, indolizidines and quinolizidines via two sequential tandem ring-closure/N-debenzylation processes. |
| title_sort | asymmetric syntheses of pyrrolizidines indolizidines and quinolizidines via two sequential tandem ring closure n debenzylation processes |
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