Kinetic resolution and parallel kinetic resolution of methyl (±)-5-alkyl-cyclopentene-1-carboxylates for the asymmetric synthesis of 5-alkyl-cispentacin derivatives Kinetic resolution and parallel kinetic resolution of methyl (±)-5-alkyl-cyclopentene-1-carboxylates for the asymmetric synthesis of 5-alkyl-cispentacin derivatives

Author
Davies, Stephen G.
Garner, A. Christopher
Long, Marcus J. C.
Morrison, Rachel M.
Roberts, Paul M.
Savory, Edward D.
Smith, Andrew D.
Sweet, Miles J.
Withey, Jonathan
Faculty Advisor
Date
2005
Keywords
kinetic resolution , parallel kinetic resolution
Abstract (summary)
Conjugate addition of lithium dibenzylamide to methyl 5-isopropyl, 5-phenyl- and 5-tert-butyl-cyclopentene-1-carboxylates occurs with high levels of substrate control (>88% de), with preferential addition to the face of the cyclic α,β-unsaturated acceptor anti- to the stereodirecting 5-alkyl substituent. Treatment of a range of methyl (±)-5-alkyl-cyclopentene-1-carboxylates with both lithium (±)-N-benzyl-N-α-methylbenzylamide and lithium (±)-N-3,4-dimethoxybenzyl-N-α-methylbenzylamide indicates significant enantiorecognition in their mutual kinetic resolutions, with preferential addition anti- to the 5-alkyl substituent, giving the 1,2-syn-1,5-anti-arrangement (E >16) after enolate protonation anti- to the amino functionality. The kinetic resolution of a range of methyl (±)-5-alkyl-cyclopentene-1-carboxylates with lithium (S)-N-benzyl-N-α-methylbenzylamide, and their efficient parallel kinetic resolution with a pseudoenantiomeric mixture of lithium (S)-N-benzyl-N-α-methylbenzylamide and lithium (R)-N-3,4-dimethoxybenzyl-N-α-methylbenzylamide are also demonstrated, giving a range of 5-alkyl-cispentacin derivatives in >98% de and high ee after N-deprotection.
Publication Information
Davies, S. G., Garner, A. C., Long, M. J., Morrison, R. M., Roberts, P. M., Savory, E. D., ... & Withey, J. M. (2005). Kinetic resolution and parallel kinetic resolution of methyl (±)-5-alkyl-cyclopentene-1-carboxylates for the asymmetric synthesis of 5-alkyl-cispentacin derivatives. Organic & Biomolecular Chemistry, 3(15), 2762-2775. doi: 10.1039/B506339F
DOI
Notes
Item Type
Article
Language
English
Rights
All Rights Reserved