Premium
Chiral syntheses of methyl ( R )‐2‐Sulfanylcarboxylic esters and acids with optical purity determination using HPLC
Author(s) -
Sasaki Ryosuke,
Tanabe Yoo
Publication year - 2018
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/chir.22860
Subject(s) - chemistry , racemization , enantiomeric excess , ethylamine , mandelic acid , catalysis , reagent , high performance liquid chromatography , isobutanol , methylamine , saponification , condensation , organic chemistry , chromatography , medicinal chemistry , enantioselective synthesis , alcohol , physics , thermodynamics
Accessible chiral syntheses of 3 types of ( R )‐2‐sulfanylcarboxylic esters and acids were performed: ( R )‐2‐sulfanylpropanoic (thiolactic) ester (53%, 98%ee) and acid (39%, 96%ee), ( R )‐2‐sulfanylsucciinic diester (59%, 96%ee), and ( R )‐2‐mandelic ester (78%, 90%ee) and acid (59%, 96%ee). The present practical and robust method involves (i) clean S N 2 displacement of methanesulfonates of ( S )‐2‐hydroxyesters by using commercially available AcSK with tris(2‐[2‐methoxyethoxy])ethylamine and (ii) sufficiently mild deacetylation. The optical purity was determined by the corresponding (2 R ,5 R )‐ trans ‐thiazolidin‐4‐one and (2 S ,5 R )‐ cis ‐thiazolidin‐4‐one derivatives based on accurate high‐performance liquid chromatography analysis with high‐resolution efficiency. Compared with the reported method utilizing AcSCs (generated from AcSH and CsCO 3 ), the present method has several advantages, that is, the use of odorless AcCOSK reagent, reasonable reaction velocity, isolation procedure, and accurate, reliable optical purity determination. The use of accessible AcSK has advantages because of easy‐to‐handle odorless and hygroscopic solid that can be used in a bench‐top procedure. The Ti(O i Pr) 4 catalyst promoted smooth trans ‐cyclo‐condensation to afford (2 R ,5 R )‐ trans ‐thiazolidin‐4‐one formation of ( R )‐2‐sulfanylcarboxylic esters with available N ‐(benzylidene)methylamine under neutral conditions without any racemization, whereas (2 S ,5 R )‐ cis ‐thiazollidin‐4‐ones were obtained via cis ‐cyclo‐condensation and no catalysts. Direct high‐performance liquid chromatography analysis of methyl ( R )‐mandelate was also performed; however, the resolution efficiency was inferior to that of the thaizolidin‐4‐one derivatizations.