Alkylierung in der 2‐Stellung von (2S, 4R)‐ 4‐Hydroxyprolin unter Retention

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