Diastereoselective Synthesis of the Nonracemic Methyl syn-(3-Fluoroalkyl)isoserinates

Cycloaddition of the (fluoroalkyl)imines 7a−c with the ketene formed in situ from (benzyloxy)acetyl chloride and triethylamine provided stereoselectively cis-(fluoroalkyl)azetidinones 5a−c in moderate yields. The corresponding N-Boc-isoserinates 11a−c and protected synthons 12a−c have been prepared from these azetidinones 5a−c. Cycloaddition of the chiral imine 18 (RF = CF3) with the same ketene led to the diastereoisomeric azetidinones 19 and 20 with a poor diastereoisomeric excess (10−20%). However, the two diastereoisomers could be easily separated by crystallization and provided enantiomerically pure N-Boc-isoserinates 23 (R,R) and 23 (S,S) after ring opening and debenzylation.