Regioselective Aminolysis and Hydrolysis of Chiral 1,4-Ferrocenyl Diacetate

The treatment of (1R,4R)-1,2-bis(phenylmethyl)ferrocenyl diacetate 2a with aqueous ammonium
in THF/MeOH at room temperature for 18 h gave the single diastereomer of the (1R,4R,Sp)-1,2-acetoamido alcohol 4a with retention of the configuration. This result showed that the aminolysis
occurred regioselectively at one side of the two acetates. Similarly, hydrolysis of the diacetate 2a
at room temperature for 18 h occurred regio- and stereoselectively to give the optically active half-ester 10 in a good yield. The ease of the substitution may depend on the geometry of the two
stereogenic centers. Only one of the acetoxy groups is suitably aligned for ionization (exo to the
ferrocenyl group) to proceed efficiently; the aminolysis takes place smoothly by iron-assisted
ionization, i.e., neighboring group participation. The leaving group on the second acetoxy group is
not suitably aligned (endo to the ferrocenyl group) and also cannot undergo a conformational change
for it to adopt the appropriate orientation for ionization to occur. This reaction is the first case of
substitution in a chiral molecule in which a conformational difference between two leaving groups
happened to affect the rate of aminolysis and hydrolysis at two stereogenic centers.