1058167-40-0Relevant academic research and scientific papers
Highly diastereoselective esterification of ketenes generated in situ from acyl chlorides with (R)-pantolactone derivatives
Yamagami, Takafumi,Hatsuda, Masanori,Utsugi, Masayuki,Kobayashi, Ryo,Moritani, Yasunori
, p. 7467 - 7470 (2013)
Our mechanistic investigations have revealed that Et3N is a key requirement for the highly diastereoselective formation of esters from the corresponding acyl chlorides with (R)-pantolactone via ketene-derived complexes. Furthermore, we have discovered that (R)-N-benzyl-pantolactam is a more effective chiral alcohol than (R)-pantolactone for the esterification of in situ generated ketenes. Ketene esterification with (R)-pantolactone derivatives is a powerful synthetic method for the synthesis of chiral α-arylpropionic acids. Our mechanistic investigations have revealed that Et3N is a key requirement for the predominant formation of ketenes from acyl chlorides, and (R)-N-benzylpantolactam was a much more effective chiral auxiliary.
Scalable synthesis of a nonracemic α-arylpropionic acid via ketene desymmetrization for a glucokinase activator
Yamagami, Takafumi,Moriyama, Noriaki,Kyuhara, Masahiro,Moroda, Atsushi,Uemura, Takeshi,Matsumae, Hiroaki,Moritani, Yasunori,Inoue, Isao
, p. 437 - 445 (2014/04/17)
Process research and development for a synthesis of the chiral carboxylic acid (R)-2 as a key intermediate of the glucokinase activator (R)-1 is described. The construction of the stereocenter at the α-carbon is a key point for the synthesis of (R)-2. The proposed process utilizes desymmetrization of a ketene in situ generated from the corresponding racemic carboxylic acid Rac-2 with (R)-pantolactone as a chiral auxiliary followed by hydrolysis of the resulting ester. This key step has been successfully scaled up to 20 kg, which demonstrates that this synthetic approach is comparable with a previously reported approach via enantioselective hydrogenation.
