Phase-Transfer-Catalyzed Asymmetric Acylimidazole Alkylation

Authors

Merritt B. Andrus, Brigham Young University
Michael A. Christiansen, Utah State UniversityFollow
Erick J. Hicken, Brigham Young University
Morgan J. Gainer, Brigham Young University
D. Karl Bedke, Brigham Young University
Kaid C. Harper, Brigham Young University
Shawn R. Mikkelson, Brigham Young University
Daniel S. Dodson, Brigham Young University
David T. Harris, Brigham Young University

Document Type

Article

Journal/Book Title

Organic Letters

Publication Date

2007

Publisher

American Chemical Society

Volume

9

Issue

23

First Page

4865

Last Page

4868

Abstract

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.

Recommended Citation

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.