A novel route to access trifluoromethylketones (TFMKs) from Weinreb amides is reported. This represents the first documented case of the Ruppert-Prakash reagent (TMS-CF(3)) reacting in a constructive manner with an amide and enables synthesis of TMFKs without risk of over-trifluoromethylation.
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http://dx.doi.org/10.1039/c2cc35037h | DOI Listing |
J Org Chem
December 2024
Medicines for All Institute, Virginia Commonwealth University, Richmond, Virginia 23284-3068, United States.
Herein, we describe a new seven-step approach to prepare ()-1-(3,6-dibromopyridin-2-yl)-2-(3,5-difluorophenyl)ethan-1-amine (()-) from the inexpensive 2-(3,5-difluorophenyl)acetic acid. The key steps in the sequence include (1) the Weinreb amide-based ketone synthesis to provide an entry point to the core structure; (2) simple functional group transformations to afford the racemic amine -; and (3) dynamic kinetic resolution (DKR) to access the chiral amine ()-. This seven-step process delivered the enantiopure amine ()- in an overall isolated yield of approximately 15%.
View Article and Find Full Text PDFJ Org Chem
November 2024
Department of Applied Chemistry, Faculty of Science, Tokyo University of Science, 1-3 Kagurazaka, Shinjuku-ku, Tokyo 162-8601, Japan.
An PrMgCl-deprotonating Weinreb amide-type Horner-Wadsworth-Emmons (HWE) reaction was developed, and the effects of diverse reaction conditions, including the base, cation, solvent, and concentration, were investigated to broaden the substrate scope and achieve high ()-selectivity. The Weinreb amide-type phosphonoenolate generated from PrMgCl was found to be isolable, stable for at least over a half year, and applicable in the HWE reaction keeping high productivity and selectivity compared with the in situ generated phosphonoenolate. The results prompted us to perform an application study including successive elongation, synthesis of a biscyclopropane, and Weinreb ketone syntheses.
View Article and Find Full Text PDFJ Org Chem
September 2024
College of Chemistry, Beijing Normal University, Beijing 100875, P. R. China.
Here, we report an efficient transition-metal-free C(sp)-C(sp) Suzuki-Miyaura-type cross-coupling between α-halo Weinreb-type amides and arylboronic acids. The reaction is carried out by capturing active aza-oxyallyl cation (AOAC) with arylboronic acid to form a boron "ate" complex, followed by 1,4-migration to give α-aryl amides with good yields.
View Article and Find Full Text PDFOrg Lett
August 2024
Institute of Chemistry, Carl von Ossietzky University Oldenburg, Carl-von-Ossietzky-Straße 9-11, 26129 Oldenburg, Germany.
Herein, we describe the application of a flow system for the generation of a soluble organo sodium compound and the transformation of this primary nucleophile with various Weinreb amides for the synthesis of alkyl-aryl ketones. Thereafter, the generation of secondary sodium intermediates, such as benzylic sodium nucleophiles or -metalated sodium nucleophiles from various carbon pre-nucleophiles, is described. These transformations generated more complex ketones, and in this investigation the key aspect was to identify factors for the chemoselective and regioselective C-H deprotonation of concurring sites within the starting material.
View Article and Find Full Text PDFChemistry
September 2024
Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, School of Pharmacy, Xuzhou Medical University, Xuzhou, China.
The catalytic direct hydroarylation of alkynamides is a highly efficient approach for accessing functionalized trisubstituted arylalkenes with amide groups. Herein, we report a rhodium-catalyzed pyridylation of alkynamides with pyridylboronic acids, producing a variety of primary, secondary, and tertiary enamides with high yields (up to 94 %). This reaction demonstrates broad tolerance towards various alkyl and aryl functional groups, providing convenient access to a diverse array of alkenylpyridine derivatives.
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