We report herein the in situ generation of difluoromethoxylated ketenimines. This novel intermediate is readily obtained from the corresponding oxime through a Beckmann rearrangement. The reactivity ...potential of this species is demonstrated as it easily undergoes addition of various nucleophiles, with a great modularity of the starting oxime. The broad applicability of this transformation leads to a chemical library of original molecules bearing −OCHF2, an Emergent Fluorinated Group (EFG).
The palladium‐catalyzed silylcyanation of ynamides is described. This reaction is fully regioselective, delivering tetrasubstituted 2‐aminoacrylonitriles derivatives exclusively. Unexpectedly, the ...nature (aryl or alkyl) of the substituent located at the β‐position of the ynamide directly controls the stereoselectivity. The reaction tolerates a number of functional groups and can be considered as the first general access to fully substituted 2‐aminoacrylonitriles. Given the singular reactivity observed, a computational study was performed to shed light on the mechanism of this intriguing transformation. Relying on the specific reactivity of the newly installed vinylsilane functionality, the scope of 2‐aminoacrylonitriles has been enlarged by postfunctionalization.
Tetrasubstituted 2‐aminoacrylonitriles (α‐enaminonitriles) are underinvestigated building blocks due to the lack of methodologies to synthesize them in a controlled manner. A general access to these valuable scaffolds accompanied by mechanistic investigations and DFT calculations is described. This highly regio‐ and stereoselective strategy relies on the use of the first intermolecular silylcyanation of ynamides.
The functionalization of 3-(difluoromethyl)pyridine has been developed via direct deprotonation of -CHF2 with a lithiated base and subsequent trapping with various electrophiles in THF. In situ ...quenching gives access to 3-pyridyl-CF2-SiMe2Ph as a new silylated compound, which can be postfunctionalized with a fluoride source to obtain a larger library of 3-(difluoroalkyl)pyridines that could not be accessed via direct deprotonation.
In this paper we are reporting the first regio- and stereoselective silylformylation of ynamides. This reaction is tolerant to a wide range of functional groups around the ynamides. The substitution ...of CO by an isocyanide makes this reaction safer and more practical than standard silylformylation reactions. It overall represents a versatile and rapid access to various tetrasubstituted 3-silyl-2-amidoacrolein derivatives. The synthetic potential of these new building blocks has been evaluated by performing several postfunctionalization.
An enantioselective direct oxygenation of propiophenone derivatives mediated by a catalytic or stoichiometric amount of new chiral non-C2-symmetric iodoarenes(III) is reported. The reaction gives an ...easy entry to optically active α-sulfonyl- and α-phosphoryl oxyketones in respectable yields and enantioselectivities.
In this paper we report the annulation reaction between 2-iodobenzaldehyde derivatives and various ynamides. This palladium-catalyzed reaction leads to rare polysubstituted amino-indenones in good ...yields with a regioselectivity up to complete. Remarkably, a regiodivergent selectivity has been identified between aryl and alkyl or silyl ynamides, with the first leading mainly to 2-amido-indenones and the second to 3-amido-indenones.
In the last few years, transition metal-mediated reactions have joined the toolbox of chemists working in the field of fluorination for Life-Science oriented research. The successful execution of ...transition metal-catalyzed carbon–fluorine bond formation has become a landmark achievement in fluorine chemistry. This rapidly growing research field has been the subject of some excellent reviews. Our approach focuses exclusively on transition metal-catalyzed reactions that allow the introduction of –CFH
2
, –CF
2
H, –C
n
F
2
n
+1
and –SCF
3
groups onto sp² carbon atoms. Transformations are discussed according to the reaction-type and the metal employed. The review will not extend to conventional non-transition metal methods to these fluorinated groups.
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► We describe the recently reported syntheses of 3-difluoromethyl pyrazoles. ► We outline the use of FAR reagents as difluoromethyl-transfer reagents. ► We detail the influence of the ...reaction conditions on regioselectivity. ► We show applications for the preparation of agrochemical ingredients.
Fluorine, the most electronegative element plays nowadays a key role in pharmaceutical, agrochemical and material sciences. It has been estimated that the number of fluorinated compounds currently under development represents some 30–50% of the total active ingredients in development. The search for new active substances with improved efficacy, lower mammalian toxicity, more favourable environmental profile and lower cost is a truly challenging task for R&D chemists within the crop protection companies. The present review will give an overview on the synthesis of pyrazoles bearing novel fluorinated substituents.
The fully regio‐ and stereoselective Zn‐catalyzed hydrocyanation of ynamides is reported and represents a general access to various trisubstituted E‐α‐enamidonitriles. The catalyst‐free ...photoisomerization selectively yields the energetically comparable Z‐stereoisomer. Finally, the synthetic potential of these new α‐enamidonitriles was evaluated through the synthesis of original heterocycles.
Trisubstituted E‐2‐amidoacrylonitriles are produced by direct hydrocyanation of ynamides. Z isomers can be obtained selectively using a thermo‐neutral catalyst‐free photoisomerization.
The use of TFEDMA, a fluoroalkyl amino reagent, for the difluoromethylation and difluoroacylation of arenes, heteroarenes, and C–H acidic compounds is reported. This approach allows for an efficient ...access to difluoromethylated products of high added value in good to excellent yields and with scale-up possibilities.
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