posted on 2003-01-23, 00:00authored byMarna C. Whisler, Peter Beak
Lithiation of N-(Boc)-N-(p-methoxyphenyl) allylic amines in the presence of (−)-sparteine provides
asymmetric homoenolate equivalents which react with electrophiles to provide highly enantioenriched enecarbamates. Acidic hydrolysis of the enecarbamates can provide the corresponding
β-substituted aldehydes. A synthetic sequence that involves a stereocontrolled intramolecular
nitrone−olefin dipolar cycloaddition has been developed for the preparation of enantioenriched
2-formyl-4-phenyl-1-aminocyclopentanes from one β-allyl-substituted aldehyde. Further manipulations allow access to an enantioenriched β-lactam. In another synthetic sequence, transmetalation
of the lithiated intermediates and reactions with aldehyde electrophiles can be controlled to afford
highly enantioenriched anti homoaldol products. Use of an anti aldehyde homoaldol product as
the chiral electrophile in an iterative reaction provides a double homoaldol product containing four
stereogenic centers with high diastereoselectivity and enantioselectivity. Reaction pathways are
proposed to account for the observed products.