Thiazolylalanine-derived catalysts for enantioselective intermolecular aldehyde-imine cross-couplings.
Catalytic asymmetric cross-coupling reactions between aldehydes and N-acylimines have been discovered that employ thiazolylalanine derivatives as catalysts. Alkylation of the thiazolyl moiety, followed by in situ generation of the derived thiazolium ylide using a tertiary amine base, leads to the active catalyst. alpha-Amidoketone products are isolated in up to 90% yield with up to 87% enantiomeric excess (>98% ee after a single recrystallization). The use of a hindered base to suppress product racemization was stimulated by a mechanistic study that revealed an isotope effect on the racemization rate of the product.
Mennen
Steven M
SM
Department of Chemistry, Merkert Chemistry Center, Boston College, Chestnut Hill, MA 02467-3860, USA.
Gipson
John D
JD
Kim
Yoona R
YR
Miller
Scott J
SJ
D000409:Alanine / Q000031:analogs & derivatives* / Q000737:chemistry; D000447:Aldehydes / Q000737:chemistry*; D002384:Catalysis; D007097:Imines / Q000138:chemical synthesis* / Q000737:chemistry*; D007659:Ketones / Q000138:chemical synthesis; D013237:Stereoisomerism; D013844:Thiazoles / Q000737:chemistry*
D000447:Aldehydes; D007097:Imines; D007659:Ketones; D013844:Thiazoles; D000409:Alanine