"Magnesium-Promoted Additions of Difluoroenolates to Unactivated Imines" by Alex L. Nguyen, Hari R. Khatri et al.

Faculty Publications

Title

Magnesium-Promoted Additions of Difluoroenolates to Unactivated Imines

Authors

Alex L. Nguyen, Department of BioMolecular Sciences , University of Mississippi , University , Mississippi 38677 , United States.
Hari R. Khatri, Department of BioMolecular Sciences , University of Mississippi , University , Mississippi 38677 , United States.
James R. Woods, Department of Medicinal Chemistry and Molecular Pharmacology , Purdue University , West Lafayette , Indiana 47907 , United States.
Cassidy S. Baldwin, Department of BioMolecular Sciences , University of Mississippi , University , Mississippi 38677 , United States.
Frank R. Fronczek, Department of Chemistry , Louisiana State University , Baton Rouge , Louisiana 70803 , United States.
David A. Colby, Department of BioMolecular Sciences , University of Mississippi , University , Mississippi 38677 , United States.

Document Type

Article

Publication Date

3-16-2018

Abstract

Although there are many synthetic methods to produce fluorinated and trifluoromethylated organic structures, the construction of difluoromethylated compounds remains a synthetic challenge. We have discovered that unactivated imines will react with difluoroenolates under exceedingly mild conditions when using magnesium salts and organic bases. We have applied this approach to the iminoaldol reaction to produce difluoromethylene groups as α,α-difluoro-β-amino-carbonyl groups. This method provides synthetically useful quantities of difficult to access α,α-difluoro-β-aminoketones without the need of protecting groups or the use of activated imines. Moreover, we have applied this strategy to create analogues of the dual orexin receptor antagonist, almorexant, in only two synthetic steps.

Publication Source (Journal or Book title)

The Journal of organic chemistry

First Page

3109

Last Page

3118

Recommended Citation

Nguyen, A. L., Khatri, H. R., Woods, J. R., Baldwin, C. S., Fronczek, F. R., & Colby, D. A. (2018). Magnesium-Promoted Additions of Difluoroenolates to Unactivated Imines. The Journal of organic chemistry, 83 (6), 3109-3118. https://doi.org/10.1021/acs.joc.7b03014

This document is currently not available here.

COinS