Parallel kinetic resolution of tert-butyl (RS)-3-oxy-substituted cyclopent-1-ene-carboxylates for the asymmetric synthesis of 3-oxy-substituted cispentacin and transpentacin derivatives.
tert-Butyl (RS)-3-methoxy- and (RS)-3-tert-butyldiphenylsilyloxy-cyclopent-1-ene-carboxylates display excellent levels of enantiorecognition in mutual kinetic resolutions with both lithium (RS)-N-benzyl-N-(alpha-methylbenzyl)amide and lithium (RS)-N-3,4-dimethoxybenzyl-N-(alpha-methylbenzyl)amide. A 50 : 50 pseudoenantiomeric mixture of lithium (S)-N-benzyl-N-(alpha-methylbenzyl)amide and lithium (R)-N-3,4-dimethoxybenzyl-N-(alpha-methylbenzyl)amide allows for the efficient parallel kinetic resolution of the tert-butyl (RS)-3-oxy-substituted cyclopent-1-ene-carboxylates, affording differentially protected 3-oxy-substituted cispentacin derivatives in high yield and >98% de. Subsequent N-deprotection and hydrolysis provides access to 3-oxy-substituted cispentacin derivatives in good yield, and in >98% de and >98% ee, while stereoselective epimerisation and subsequent deprotection affords the corresponding transpentacin analogues in good yield, and in >98% de and >98% ee.
Aye
Yimon
Y
Department of Chemistry, Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford, UK.
Davies
Stephen G
SG
Garner
A Christopher
AC
Roberts
Paul M
PM
Smith
Andrew D
AD
Thomson
James E
JE
D002264:Carboxylic Acids / Q000737:chemistry*; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry; D007700:Kinetics; D008958:Models, Molecular
D002264:Carboxylic Acids; D003515:Cycloleucine; C065594:cispentacin