Kinetic resolution of tert-butyl (RS)-3-alkylcyclopentene-1-carboxylates for the synthesis of homochiral 3-alkyl-cispentacin and 3-alkyl-transpentacin derivatives
| dc.contributor.author | Bunnage, Mark E. | |
| dc.contributor.author | Davies, Stephen G. | |
| dc.contributor.author | Parkin, Richard M. | |
| dc.contributor.author | Roberts, Paul M. | |
| dc.contributor.author | Smith, Andrew D. | |
| dc.contributor.author | Withey, Jonathan M. | |
| dc.date.accessioned | 2016-01-12 | |
| dc.date.accessioned | 2022-05-27T01:13:49Z | |
| dc.date.available | 2022-05-27T01:13:49Z | |
| dc.date.issued | 2004 | |
| dc.description.abstract | 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, Pr-i, Bu-t) with lithium (RS)-N-benzyl-N-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-Pr-i 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, Pr-i, Bu-t) 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, Pr-i) 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, Pr-i, Bu-t) by treatment with (KOBu)-Bu-t in (BuOH)-Bu-t 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. | |
| dc.description.uri | http://library.macewan.ca/cgi-bin/SFX/url.pl/7M9 | |
| dc.identifier.citation | Bunnage, M., Davies, S., Parkin, R., Roberts, P., Smith, A., & Withey, J. (2004). Kinetic resolution of tert-butyl (RS)-3-alkylcyclopentene-1-carboxylates for the synthesis of homochiral 3-alkyl-cispentacin and 3-alkyl-transpentacin derivatives. Organic & Biomolecular Chemistry, 2(22), 3337-3354. doi:10.1039/B407559E | |
| dc.identifier.doi | https://doi.org/10.1039/B407559E | |
| dc.identifier.uri | https://hdl.handle.net/20.500.14078/283 | |
| dc.language | English | |
| dc.language.iso | en | |
| dc.rights | All Rights Reserved | |
| dc.subject | helical secondary structure | |
| dc.subject | beta-amino acid | |
| dc.subject | meisenheimer rearrangement protocol | |
| dc.subject | asymmetric conjugate addition | |
| dc.title | Kinetic resolution of tert-butyl (RS)-3-alkylcyclopentene-1-carboxylates for the synthesis of homochiral 3-alkyl-cispentacin and 3-alkyl-transpentacin derivatives | en |
| dc.title | Kinetic resolution | en |
| dc.type | Article |