Parallel kinetic resolution of tert-butyl (RS)-3-alkyl-cyclopentene-1-carboxylates for the asymmetric synthesis of 3-alkyl-cispentacin derivatives.
The double mutual kinetic resolution of tert-butyl (RS)-3-benzyl-cyclopentene-1-carboxylate with a 50 : 50 mixture of lithium (RS)-N-benzyl-N-alpha-methylbenzylamide and lithium (RS)-N-3,4-dimethoxybenzyl-N-alpha-methylbenzylamide gives, after protonation with 2,6-di-tert-butylphenol, a 50 : 50 mixture of the readily separable N-benzyl-(1SR,2RS,3RS,alphaRS)- and N-3,4-dimethoxybenzyl-(1SR,2RS,3RS,alphaRS)-beta-amino esters in >98% de in each case. This product distribution indicates that these amides react at very similar rates and with no mutual interference to furnish readily separable products, and are thus ideal for parallel kinetic resolution. The efficient parallel kinetic resolution (E > 65) of a range of tert-butyl (RS)-3-alkyl-cyclopentene-1-carboxylates with a pseudoenantiomeric mixture of homochiral lithium (S)-N-benzyl-N-alpha-methylbenzylamide and lithium (R)-N-3,4-dimethoxybenzyl-N-alpha-methylbenzylamide gives, after separation and N-deprotection, a range of carboxylate protected 3-alkyl-cispentacin derivatives in >98% de and >95% ee.
Davies
Stephen G
SG
Department of Chemistry, University of Oxford, Chemistry Research Laboratory, Mansfield Road, Oxford OX1 3TA, UK. steve.davies@chem.ox.ac.uk
Garner
A Christopher
AC
Long
Marcus J C
MJ
Smith
Andrew D
AD
Sweet
Miles J
MJ
Withey
Jonathan M
JM
D000577:Amides / Q000737:chemistry; D002625:Chemistry, Organic / Q000379:methods*; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000737:chemistry; D007700:Kinetics; D018020:Lithium Compounds / Q000737:chemistry; D013237:Stereoisomerism
D000577:Amides; D018020:Lithium Compounds; D003515:Cycloleucine; C065594:cispentacin