Consecutive catalytic electrophilic fluorination/amination of β-keto esters: toward α-fluoro-α-amino acids?

Stereoselective Reduction of α‐Fluoro‐β‐keto Esters by NADH and NADPH‐Dependent Ketoreductases

“…For at least two substrates, 1a and 1g, reduction is rapid and quantitative, with reaction complete in less than 10 min. [36,37] Experimental Section Synthesis of racemic 2-fluoro-3-hydroxy esters: Racemic 2b-2i were synthesized by Reformatsky reactions using zinc dust, ethyl bromofluoroacetate and the corresponding aldehyde as described in the literature. The presence of the 19 F nucleus allows for convenient in situ 19 F NMR monitoring of the enzyme reaction, as well as convenient analysis of Mosher ester products for stereochemical assignments and quantification.…”

“…[35] Such intermediates may also prove useful toward synthesis of α-fluoro-α-amino acids. [36,37] Experimental Section Synthesis of racemic 2-fluoro-3-hydroxy esters: Racemic 2b-2i were synthesized by Reformatsky reactions using zinc dust, ethyl bromofluoroacetate and the corresponding aldehyde as described in the literature. [28,29] See Supporting Information for experimental procedure, yield data and NMR characterization, including 1 H, 13 C, and 19 F NMR spectra.…”

Lanthanides-pybox: An Excellent Combination for Highly Enantioselective Electrophilic α-Amination of Acyclic β-Keto Esters. Isolation of Ternary Pybox/Ln/β-Keto Ester Complexes

“…Especially remarkable are the results obtained by the group of K. A. Jørgensen, using a combination Cu(OTf) 2 /( S,S )‐Ph‐box in the amination of acyclic α‐alkyl β‐keto esters using dibenzyl azodicarboxylate . This methodology was also applied in tandem with a palladium catalyst for the synthesis of pyrazolidines and in the consecutive electrophilic fluorination/amination . Another related system includes the use of a C 3 ‐symmetric tris(oxazoline) with Cu(OTf) 2 for the amination of ethyl 2‐methylacetoacetate …”

Enantioselective α-hydrazination of α-fluoro-β-ketoesters catalyzed by chiral nickel complexes

“…Several groups presented the direct enantioselective amination of active methine compounds such as bketoester [7], b-ketophosphonates [8], a-cyanoacetates [9], and a-cyanoketones [10] in the presence of chiral metal complexes or organocatalysts. Recently, Togni reported hydrazination of a-fluoro-b-ketoesters using chiral Cu-bisoxazoline complexes afforded a-fluoro-a-hydrazino-b-ketoesters [11]. While several efficient asymmetric amination reactions using chiral Lewic acids have been developed, a drawback is that most Lewis acids are unstable in the presence of water and even sensitive to moisture.…”