Asymmetric aza-[2,3]-Wittig sigmatropic rearrangements: chiral auxiliary control and formal asymmetric synthesis of (2S, 3R, 4R)-4-hydroxy-3-methylproline and (-)-kainic acid.
A survey of 16 different chiral auxiliaries and a variety of strategies found that an (-)-8-phenylmenthol ester of a glycine derived migrating group can control the absolute stereochemistry of aza-[2,3]-Wittig sigmatropic rearrangements with diastereoselectivities of ca. 3 : 1 with respect to the auxiliary. In two specific examples, ca. 50% yields of enantiomerically pure products were obtained after chromatographic purification. These were synthetically manipulated with no erosion of stereochemistry into intermediates that completed formal asymmetric syntheses of (+)-HyMePro and (-)-kainic acid.
Anderson
James C
JC
School of Chemistry, University of Nottingham, Nottingham, UK NG7 2RD. j.anderson@nottingham.ac.uk
O'Loughlin
Julian M A
JM
Tornos
James A
JA
D007608:Kainic Acid / Q000138:chemical synthesis* / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D011392:Proline / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D021241:Spectrometry, Mass, Electrospray Ionization; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013237:Stereoisomerism
C511300:(2S, 3R, 4R)-4-hydroxy-3-methylproline; D011392:Proline; D007608:Kainic Acid