Alkylation in the 2-Position of (2S,4R)-4-Hydroxyproline with Retention of Configuration

Article abstract of DOI:10.1002/hlca.19850680119

O-Acetyl-4-hydroxyproline (1b) is condensed with pivalaldehyde to give a single stereoisomer of the 2-(tert-butyl)-4-oxo-3-oxa-1-azabicyclo<3.3.0>oct-7-yl acetate (3).This is converted to the enolates 4 or 5, reactions of which with alkyl halides, aldehydes, and acetone (-->6,9,10,11) are diastereoselective (lk-1,3-induction).Cleavage of the corresponding products furnishes the enantiomerically pure 2-deuterio-, 2-methyl-, 2-allyl-, and 2-benzyl-substituted 4-hydroxyprolines 2a-2d.