Synthesis of new chiral sulfinyldiacetic acid derivatives and attempt at chemoselective asymmetric Pummerer reaction.
(R(S))-1 (85% ee) was prepared by utilizing a porcin pancreatic lipase-promoted hydrolysis of sulfinyldiacetic acid dimethyl ester (8) which was derived from thiodiacetic acid (7). (R(S))-1 (99% ee) and (S(S))-1 (99% ee) were readily obtained by methanolysis of (R(S),S)-12 and (S(S),S)-12 with MeONa in MeOH. (R(S),S)-12 and (S(S),S)-12 were furnished by chromatographic separation of the diastereomeric mixture, obtained by oxidation of thiodiacetic mono-carboxylic acid (11) with 30% H2O2 followed by dehydrative condensation of the resultant sulfinyldiacetic mono-carboxylic acid with 4(S)-isopropyl-1,3-thiazolidine-2-thione. (R(S))-1 (99% ee) was successively treated with (TMS)2NLi, Ac2O, and TMSOTf to give a major chiral-3 product in 75% ee and in a highly chemoselective manner (chiral-3:chiral-2=93:7).
Nagao
Yoshimitsu
Y
Faculty of Pharmaceutical Sciences, The University of Tokushima, Japan. ynagao@ph2.tokushima-u.ac.jp
Miyamoto
Satoshi
S
Hayashi
Kazuhiko
K
Mihira
Ado
A
Sano
Shigeki
S
D000818:Animals; D002417:Cattle; D006868:Hydrolysis; D008049:Lipase / Q000737:chemistry*; D010179:Pancreas / Q000201:enzymology; D013237:Stereoisomerism; D013552:Swine; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry*
D013844:Thiazoles; D008049:Lipase