Kinetic resolution of the racemic 2-hydroxyalkanoates using the enantioselective mixed-anhydride method with pivalic anhydride and a chiral acyl-transfer catalyst.
A variety of optically active 2-hydroxyalkanoates and the corresponding 2-acyloxyalkanoates are produced by the kinetic resolution of racemic 2-hydroxyalkanoates by using achiral 2,2-diarylacetic acid with hindered carboxylic anhydrides as the coupling reagents. The combined use of diphenylacetic acid, pivalic anhydride, and (+)-(R)-benzotetramisole ((R)-BTM) effectively produces (S)-2-hydroxyalkanoates and (R)-2-acyloxyalkanoates from the racemic 2-hydroxyalkanoates (s-values=47-202). This protocol directly provides the desired chiral 2-hydroxyalkanoate derivatives from achiral diarylacetic acid and racemic secondary alcohols that do not include the sec-phenethyl alcohol moiety by using the transacylation process to generate the mixed anhydrides from the acid components with bulky carboxylic anhydrides under the influence of the chiral acyl-transfer catalyst. The transition state that provides the desired (R)-2-acyloxyalkanoate from (R)-2-hydroxyalkanoate included in the racemic mixture is disclosed by DFT calculations, and the structural features of the transition form are also discussed.
Shiina
Isamu
I
Department of Applied Chemistry, Faculty of Science, Tokyo University of Science, Kagurazaka, Shinjuku-ku, Tokyo 162-8601, Japan. shiina@rs.kagu.tus.ac.jp
Nakata
Kenya
K
Ono
Keisuke
K
Sugimoto
Masuhiro
M
Sekiguchi
Akihiro
A
D000473:Alkanes / Q000737:chemistry*; D000812:Anhydrides / Q000737:chemistry*; D002384:Catalysis; D007700:Kinetics; D015394:Molecular Structure; D010421:Pentanoic Acids / Q000737:chemistry*; D013237:Stereoisomerism
D000473:Alkanes; D000812:Anhydrides; D010421:Pentanoic Acids; C048464:pivalic anhydride