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Kinetic resolution of α‐acetoxy carboxylic acids with homochiral SuperQuats
Author(s) -
Bew Sean P.,
Davies Stephen G.,
Fukuzawa Shinichi
Publication year - 2000
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/(sici)1520-636x(2000)12:5/6<483::aid-chir33>3.0.co;2-d
Subject(s) - chemistry , isopropyl , mandelic acid , kinetic resolution , lithium chloride , chloride , carboxylic acid , lithium (medication) , medicinal chemistry , salt (chemistry) , organic chemistry , stereochemistry , catalysis , enantioselective synthesis , medicine , endocrinology
Preliminary investigations focused on the kinetic resolution of (±)‐α‐acetoxy mandelic carboxylic acid chloride with iso propyl SuperQuat and iso propyl Evans' homochiral auxiliaries. The addition of 2 equiv. of the acid chloride to the lithium salts of the auxiliaries (SuperQuat and Evans') at −100°C in the THF afforded the corresponding N‐acyl auxiliaries in high chemical yields (95% and 89%) and d.e. 's of 66% and 40%, respectively. Using the same mandelic acid chloride but incorporating SuperQuat auxiliaries derived from ( S )‐phenylglycine and ( S )‐phenylalanine yielded the corresponding N‐acyl SuperQuats in 86% and 90% and d.e. 's of 66% and 30%, respectively. Substituting the phenyl group within the α‐acetoxy mandelic acid chloride for a n ‐butyl, tert ‐butyl and cyclohexyl group changed the d.e. significantly when kinetically resolved with iso propyl SuperQuat. The yields were all similar, i.e., ∼90% but the d.e. 's varied considerably, with values of 20%, 50%, and 82%, respectively. Attempted kinetic resolution of α‐methoxyphenylacetyl chloride using the lithium salt of iso propyl SuperQuat revealed a diasteroselectivity of 45%, significantly lower than that obtained with the corresponding α‐acetoxy carboxylic acid chlorides. Chirality 12:483–487, 2000. © 2000 Wiley‐Liss, Inc.