Phase-Transfer-Catalyzed Asymmetric Acylimidazole Alkylation
American Chemical Society
2-Acylimidazoles are alkylated under phase-transfer conditions with cinchonidinium catalysts at −40 °C with allyl and benzyl electrophiles in high yield with excellent enantioselectivity (79 to >99% ee). The acylimidazole substrates are made in three steps from bromoacetic acid via the N-acylmorpholine adduct. The catalyst is made in high purity allowing for S-product formation (6−20 h) under mild conditions, consistent with an ion-pair mechanism. The products are readily converted to useful ester products using methyltriflate and sodium methoxide, via a dimethylacylimidazolium intermediate without racemization. The process is efficient, direct, and amenable to other electrophiles and transformations that proceed through an enolate intermediate.
Andrus, M. B.; Christiansen, M. A.; Hicken, E. J.; Gainer, M. J.; Bedke, D. K.; Harper, K. C.; Mikkelson, S. R.; Dodson, D. S.; Harris, D. T. “Phase-Transfer-Catalyzed Asymmetric Acylimidazole Alkylation.” Org. Lett. 2007, 9, 4865-4868.