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.
Fukuzawa
Shin-ichi
S
Department of Applied Chemistry, Institute of Science and Engineering, Chuo University, 1-13-27 Kasuga, Bunkyo-ku, Tokyo 112-8551, Japan. fukuzawa@kc.chuo-u.ac.jp
Wachi
Daisuke
D
Suzuki
Takashi
T
Itoh
Satoshi
S