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

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