Kinetic resolution of tert-butyl (RS)-3-alkylcyclopentene-1-carboxylates for the synthesis of homochiral 3-alkyl-cispentacin and 3-alkyl-transpentacin derivatives.
High levels of stereocontrol are observed in the conjugate addition of lithium dibenzylamide to tert-butyl (RS)-3-alkylcyclopentene-1-carboxylates (alkyl = Et, Bn), with addition occurring exclusively anti- to the 3-alkyl substituent. Treatment of a range of tert-butyl (RS)-3-alkylcyclopentene-1-car...
| Hauptverfasser: | , , , , , |
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| Format: | Journal article |
| Sprache: | English |
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2004
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| _version_ | 1826295731906936832 |
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| author | Bunnage, M Davies, S Parkin, R Roberts, P Smith, A Withey, J |
| author_facet | Bunnage, M Davies, S Parkin, R Roberts, P Smith, A Withey, J |
| author_sort | Bunnage, M |
| collection | OXFORD |
| description | High levels of stereocontrol are observed in the conjugate addition of lithium dibenzylamide to tert-butyl (RS)-3-alkylcyclopentene-1-carboxylates (alkyl = Et, Bn), with addition occurring exclusively anti- to the 3-alkyl substituent. Treatment of a range of tert-butyl (RS)-3-alkylcyclopentene-1-carboxylates (alkyl = Et, Bn, (i)Pr, (t)Bu) with lithium (RS)-N-benzyl-N-[small alpha]-methylbenzylamide indicates that good enantiorecognition is observed (E > 80) in their mutual kinetic resolution. In these reactions, conjugate addition of the lithium amide occurs exclusively anti- to the 3-alkyl substituent, with subsequent C(1)-protonation occurring preferably anti- to the 2-amino group in the 3-Et, 3-Bn and 3-(i)Pr cases, giving predominantly the corresponding 1,2-syn-2,3-anti-diastereoisomers. Conjugate addition to (RS)-3-tert-butyl cyclopentene-1-carboxylate results in exclusive 2,3-anti -addition and a reversal in C(1)-protonation selectivity, giving predominantly the 1,2-anti-2,3-anti-diastereoisomer. Furthermore, the kinetic resolution of the tert-butyl (RS)-3-alkylcyclopentene-1-carboxylates (alkyl = Et, Bn, (i)Pr, (t)Bu) with lithium (S)-N-benzyl-N-alpha-methylbenzylamide proceeds efficiently, giving, at between 47 and 51% conversion, the resolved 3-alkylcyclopentene-1-carboxylates in >85 to >98% ee and the beta-amino ester products of conjugate addition in high de, consistent with E > 80 in each case. Subsequent deprotection of the 1,2-syn-2,3-anti-3-alkyl-beta-amino esters (alkyl = Et, Bn, (i)Pr) by hydrogenolysis and ester hydrolysis gives the corresponding 1,2-syn-2,3-anti-3-alkylcispentacins in >98% de and 98 +/- 1% ee. Selective epimerisation of the 1,2-syn-2,3-anti-3-alkyl-beta-amino esters (alkyl = Et, Bn, (i)Pr, (t)Bu) by treatment with KO(t)Bu in (t)BuOH gives the corresponding 1,2-anti-2,3-anti-3-alkyl-beta-amino esters in quantitative yield and in >98% de, with subsequent deprotection by hydrogenolysis and ester hydrolysis giving the corresponding 1,2-anti-2,3-anti-3-alkylcispentacin hydrochlorides in >98% de. |
| first_indexed | 2024-03-07T04:05:34Z |
| format | Journal article |
| id | oxford-uuid:c605d986-15e9-4a3d-a054-6cec12d30bb4 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T04:05:34Z |
| publishDate | 2004 |
| record_format | dspace |
| spelling | oxford-uuid:c605d986-15e9-4a3d-a054-6cec12d30bb42022-03-27T06:35:14ZKinetic resolution of tert-butyl (RS)-3-alkylcyclopentene-1-carboxylates for the synthesis of homochiral 3-alkyl-cispentacin and 3-alkyl-transpentacin derivatives.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:c605d986-15e9-4a3d-a054-6cec12d30bb4EnglishSymplectic Elements at Oxford2004Bunnage, MDavies, SParkin, RRoberts, PSmith, AWithey, JHigh levels of stereocontrol are observed in the conjugate addition of lithium dibenzylamide to tert-butyl (RS)-3-alkylcyclopentene-1-carboxylates (alkyl = Et, Bn), with addition occurring exclusively anti- to the 3-alkyl substituent. Treatment of a range of tert-butyl (RS)-3-alkylcyclopentene-1-carboxylates (alkyl = Et, Bn, (i)Pr, (t)Bu) with lithium (RS)-N-benzyl-N-[small alpha]-methylbenzylamide indicates that good enantiorecognition is observed (E > 80) in their mutual kinetic resolution. In these reactions, conjugate addition of the lithium amide occurs exclusively anti- to the 3-alkyl substituent, with subsequent C(1)-protonation occurring preferably anti- to the 2-amino group in the 3-Et, 3-Bn and 3-(i)Pr cases, giving predominantly the corresponding 1,2-syn-2,3-anti-diastereoisomers. Conjugate addition to (RS)-3-tert-butyl cyclopentene-1-carboxylate results in exclusive 2,3-anti -addition and a reversal in C(1)-protonation selectivity, giving predominantly the 1,2-anti-2,3-anti-diastereoisomer. Furthermore, the kinetic resolution of the tert-butyl (RS)-3-alkylcyclopentene-1-carboxylates (alkyl = Et, Bn, (i)Pr, (t)Bu) with lithium (S)-N-benzyl-N-alpha-methylbenzylamide proceeds efficiently, giving, at between 47 and 51% conversion, the resolved 3-alkylcyclopentene-1-carboxylates in >85 to >98% ee and the beta-amino ester products of conjugate addition in high de, consistent with E > 80 in each case. Subsequent deprotection of the 1,2-syn-2,3-anti-3-alkyl-beta-amino esters (alkyl = Et, Bn, (i)Pr) by hydrogenolysis and ester hydrolysis gives the corresponding 1,2-syn-2,3-anti-3-alkylcispentacins in >98% de and 98 +/- 1% ee. Selective epimerisation of the 1,2-syn-2,3-anti-3-alkyl-beta-amino esters (alkyl = Et, Bn, (i)Pr, (t)Bu) by treatment with KO(t)Bu in (t)BuOH gives the corresponding 1,2-anti-2,3-anti-3-alkyl-beta-amino esters in quantitative yield and in >98% de, with subsequent deprotection by hydrogenolysis and ester hydrolysis giving the corresponding 1,2-anti-2,3-anti-3-alkylcispentacin hydrochlorides in >98% de. |
| spellingShingle | Bunnage, M Davies, S Parkin, R Roberts, P Smith, A Withey, J Kinetic resolution of tert-butyl (RS)-3-alkylcyclopentene-1-carboxylates for the synthesis of homochiral 3-alkyl-cispentacin and 3-alkyl-transpentacin derivatives. |
| title | Kinetic resolution of tert-butyl (RS)-3-alkylcyclopentene-1-carboxylates for the synthesis of homochiral 3-alkyl-cispentacin and 3-alkyl-transpentacin derivatives. |
| title_full | Kinetic resolution of tert-butyl (RS)-3-alkylcyclopentene-1-carboxylates for the synthesis of homochiral 3-alkyl-cispentacin and 3-alkyl-transpentacin derivatives. |
| title_fullStr | Kinetic resolution of tert-butyl (RS)-3-alkylcyclopentene-1-carboxylates for the synthesis of homochiral 3-alkyl-cispentacin and 3-alkyl-transpentacin derivatives. |
| title_full_unstemmed | Kinetic resolution of tert-butyl (RS)-3-alkylcyclopentene-1-carboxylates for the synthesis of homochiral 3-alkyl-cispentacin and 3-alkyl-transpentacin derivatives. |
| title_short | Kinetic resolution of tert-butyl (RS)-3-alkylcyclopentene-1-carboxylates for the synthesis of homochiral 3-alkyl-cispentacin and 3-alkyl-transpentacin derivatives. |
| title_sort | kinetic resolution of tert butyl rs 3 alkylcyclopentene 1 carboxylates for the synthesis of homochiral 3 alkyl cispentacin and 3 alkyl transpentacin derivatives |
| work_keys_str_mv | AT bunnagem kineticresolutionoftertbutylrs3alkylcyclopentene1carboxylatesforthesynthesisofhomochiral3alkylcispentacinand3alkyltranspentacinderivatives AT daviess kineticresolutionoftertbutylrs3alkylcyclopentene1carboxylatesforthesynthesisofhomochiral3alkylcispentacinand3alkyltranspentacinderivatives AT parkinr kineticresolutionoftertbutylrs3alkylcyclopentene1carboxylatesforthesynthesisofhomochiral3alkylcispentacinand3alkyltranspentacinderivatives AT robertsp kineticresolutionoftertbutylrs3alkylcyclopentene1carboxylatesforthesynthesisofhomochiral3alkylcispentacinand3alkyltranspentacinderivatives AT smitha kineticresolutionoftertbutylrs3alkylcyclopentene1carboxylatesforthesynthesisofhomochiral3alkylcispentacinand3alkyltranspentacinderivatives AT witheyj kineticresolutionoftertbutylrs3alkylcyclopentene1carboxylatesforthesynthesisofhomochiral3alkylcispentacinand3alkyltranspentacinderivatives |