Competing C–H and C–F bond activation reactions of a fluorinated olefin at Rh: a fluorido vinylidene complex as an intermediate in an unprecedented dehydrofluorination step

Dehydrofluorination of a fluorinated vinyl ligand takes place after C–H bond activation of Z-1,3,3,3-tetrafluropropene at a rhodium vinyl complex. Model studies support a vinylidene as reaction intermediate for the dehydrofluorination.

Synthesis and Application of Chiral Palladium-Phosphane Precatalyst in Enantioselective C-N Cross-Coupling

The various strategies and reaction conditions towards the synthesis of benzene-, naphthalene-, and phenanthrene-based dicyclohexylbiaryl phosphanes are presented. A chiral third generation Buchwald-type precatalyst has been synthesized, employing the non-commercially available ligand, (R)-dicyclohexyl(2'-methoxy-[1,1'-binaphth-2-yl])phosphane, (R)-Cy2MOP, and a dimeric methanesulfonate-bridged palladacycle based on a 2-aminobiphenyl scaffold. Application of the palladacyclic precatalyst in an enantioselective variant of the BuchwaldHartwig reaction is demonstrated in the desymmetrization of prochiral α-(2-bromobenzyl)malonamides via intramolecular N-arylation. The scope of the catalysis in the presence of the precatalyst has been investigated with efforts towards optimizing yields, catalyst loading, and enantioselectivities. Attempts towards the isolation of a potential reaction intermediate in the form of a stable amido-bound palladium complex are discussed. Finally, strategies towards gaining mechanistic insight on the origin of the enantiomeric excess are discussed.

Synthesis and Application of Chiral Palladium-Phosphane Precatalyst in Enantioselective C-N Cross-Coupling

The various strategies and reaction conditions towards the synthesis of benzene-, naphthalene-, and phenanthrene-based dicyclohexylbiaryl phosphanes are presented. A chiral third generation Buchwald-type precatalyst has been synthesized, employing the non-commercially available ligand, (R)-dicyclohexyl(2'-methoxy-[1,1'-binaphth-2-yl])phosphane, (R)-Cy2MOP, and a dimeric methanesulfonate-bridged palladacycle based on a 2-aminobiphenyl scaffold. Application of the palladacyclic precatalyst in an enantioselective variant of the BuchwaldHartwig reaction is demonstrated in the desymmetrization of prochiral α-(2-bromobenzyl)malonamides via intramolecular N-arylation. The scope of the catalysis in the presence of the precatalyst has been investigated with efforts towards optimizing yields, catalyst loading, and enantioselectivities. Attempts towards the isolation of a potential reaction intermediate in the form of a stable amido-bound palladium complex are discussed. Finally, strategies towards gaining mechanistic insight on the origin of the enantiomeric excess are discussed.

Theoretical insight on the treatment of β-hexachlorocyclohexane waste through alkaline dehydrochlorination

The occurrence of 4.8–7.2 million tons of hexachlorocyclohexane (HCH) isomers stocked in dumpsites around the world constitutes a huge environmental and economical challenge because of their toxicity and persistence. Alkaline treatment of an HCH mixture in a dehydrochlorination reaction is hampered by the low reactivity of the β-HCH isomer (HCl elimination unavoidably occurring through syn H–C–C–Cl arrangements). More intriguingly, the preferential formation of 1,2,4-trichlorobenzene in the β-HCH dehydrochlorination reaction (despite the larger thermodynamical stability of the 1,3,5-isomer) has remained unexplained up to now, though several kinetic studies had been reported. In this paper, we firstly show a detailed Density Functional study on all paths for the hydroxide anion-induced elimination of β-HCH through a three-stage reaction mechanism (involving two types of reaction intermediates). We have now demonstrated that the first reaction intermediate can follow several alternative paths, the preferred route involving abstraction of the most acidic allylic hydrogen which leads to a second reaction intermediate yielding only 1,2,4-trichlorobenzene as the final reaction product. Our theoretical results allow explaining the available experimental data on the β-HCH dehydrochlorination reaction (rate-determining step, regioselectivity, instability of some reaction intermediates).

Structural and mechanistic basis for protein glutamylation by the kinase fold

The kinase domain transfers phosphate from ATP to substrates. However, the Legionella effector SidJ adopts a kinase fold yet catalyzes calmodulin (CaM)-dependent glutamylation to inactivate the SidE ubiquitin ligases. The structural and mechanistic basis in which the kinase domain catalyzes protein glutamylation is unknown. Here we present cryo-EM reconstructions of SidJ:CaM:SidE reaction intermediate complexes. We show that the kinase-like active site of SidJ adenylates an active site Glu in SidE resulting in the formation of a stable reaction intermediate complex. An insertion in the catalytic loop of the kinase domain positions the donor Glu near the acyl-adenylate for peptide bond formation. Our structural analysis led us to discover that the SidJ paralog SdjA is a glutamylase that differentially regulates the SidE-ligases during Legionella infection. Our results uncover the structural and mechanistic basis in which the kinase fold catalyzes non-ribosomal amino acid ligations and reveal an unappreciated level of SidE-family regulation.