Parallel synthesis of oxazolines and thiazolines by tandem condensation-cyclodehydration of carboxylic acids with amino alcohols and aminothiols.
A combinatorial library of oxazolines and thiazolines was synthesized in moderate to excellent yields using a newly developed methodology. Free carboxylic acids were directly condensed with amino alcohols and aminothiols in the presence of 3-nitrophenylboronic acid as a dehydration catalyst. The library synthesis illustrates the scope of this process: After traditional reaction optimization, a total of 17 oxazolines and 6 thiazolines were successfully prepared in a 24-reaction setup in a Radleys GreenHouse parallel synthesizer. The yields of the parallel reactions ranged from moderate to excellent, depending largely on carboxylate reactivity and functionalization, and generally exceeded those of the traditional reaction setup. The target compounds were isolated in high purities (average purity is 96% according to GC analysis) after passing reaction mixtures through short PrepSep SPE Florisil cartridges.
Wipf
Peter
P
Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.
Wang
Xiaodong
X
D000605:Amino Alcohols / Q000737:chemistry*; D001897:Boronic Acids / Q000737:chemistry; D002264:Carboxylic Acids / Q000737:chemistry*; D020650:Combinatorial Chemistry Techniques; D003500:Cyclization; D010080:Oxazoles / Q000138:chemical synthesis*; D013438:Sulfhydryl Compounds / Q000737:chemistry; D013844:Thiazoles / Q000138:chemical synthesis*
D000605:Amino Alcohols; D001897:Boronic Acids; D002264:Carboxylic Acids; D010080:Oxazoles; D013438:Sulfhydryl Compounds; D013844:Thiazoles; C017562:3-nitrobenzeneboronic acid