Work

Magnesium-Promoted Additions of Difluoroenolates to Unactivated Imines

Year: 2018

Type: article

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.

Source: The Journal of Organic Chemistry

DOI: 10.1021/acs.joc.7b03014

Authors: Alex L. Nguyen, Hari R. Khatri, James R. Woods, Cassidy S. Baldwin, Frank R. Fronczek, David A. Colby

Institutions: University of Mississippi, Purdue University West Lafayette, Louisiana State University

Language: English

Topic: Fluorine in Organic Chemistry

Subfield: Pharmaceutical Science

Field: Pharmacology, Toxicology and Pharmaceutics

Domain: Life Sciences

Open Access status: green

Funders: University of Mississippi, National Institutes of Health, National Institute of General Medical Sciences

Award: Center of Research Excellence in Natural Products Neuroscience (CORE-NPN)