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Preparative resolutions of an α‐methyl carboxylic acid through selective transformations of readily epimerizable intermediates
Author(s) -
Josef Kurt A.,
D'Ambra Thomas E.,
Rosi David,
Philion Richard E.
Publication year - 1990
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.530020108
Subject(s) - chemistry , racemization , acylation , diastereomer , hydrolysis , kinetic resolution , yield (engineering) , organic chemistry , friedel–crafts reaction , substrate (aquarium) , resolution (logic) , enantiomer , carboxylic acid , chromatography , enantioselective synthesis , catalysis , materials science , oceanography , artificial intelligence , geology , computer science , metallurgy
Two preparations of the enantiomers of 2 are described. The first makes use of the chromatographic separation of the diastereomeric amides 6a and 6b. Standard hydrolysis of these amides caused racemization, so a milder sequence was developed which utilized carbonyldiimidazole and 1 equivalent of 1 N LiOH. The second preparation involved classical resolution of 9 with (−)‐cinchonidine. Subsequent transformations of this substrate involved ester formation, Friedel–Crafts acylation, and ester hydrolysis, all without racemization. The most notable of these reactions was the use of EtAlCl 2 in the Friedel–Crafts step, which provided a mild acylation of 10. This second preparation affords a high yield, mild process for the potential preparation of kilogram quantities of (−)‐(R)‐2b.