Mechanistic Implications of the Observation of Kinetic Resolution in a Palladium-Catalyzed Enantioselective Allylic Alkylation.

Preferential rotation in substrate-palladium intermediates in a catalyzed asymmetric allylic alkylation is proposed to be responsible for both the observed kinetic resolution of the racemic allylic acetate starting material as well as the high selectivity found in the enantiodiscriminating product-forming step [Eq. (a)].

Versatile Ligands for Palladium-Catalyzed Asymmetric Allylic Alkylation.

Palladium complexes of the chiral diphosphanes 1 and 2 which possess a rigid backbone and a large bite angle catalyze the alkylation of allyl compounds with both high enantioselectivities and reaction rates, particularly with less sterically demanding substrates. 1: R=Me, X=S; 2: R=H, X=C(CH3 )2 .

Palladium(0)-catalyzed trimerization of arylisocyanates into 1,3,5-triarylisocyanurates in the presence of diimines: a nonintuitive mechanism.

We show here that palladium(0) (dibenzylideneacetone) complexes bearing 1,10-phenanthroline constitute efficient catalysts for the cyclotrimerization of aromatic isocyanates. For the first time, the mechanism of this reaction has been investigated experimentally and theoretically with group 10 catalysts. This investigation provides a very consistent picture of the catalytic cycle. Notably, we establish that the reaction does not proceed by stepwise cycloadditions or ring insertions involving metallacyclic intermediates, as might have been anticipated. Rather, in our proposal, the initial steps of the mechanism resemble the chain-growth process operative during the anionic polymerization of isocyanates and feature charge-separated intermediates. These steps are then followed by ring closure on the metal center of the last intermediate formed to yield a seven-membered metallacycle that reductively eliminates the cyclotrimer and re-forms the active species. In addition, we conclusively show that the (known) palladacycles that could be isolated during the experimental investigations are not catalytic intermediates but result from catalyst deactivation. Thus, with Pd(0) diimine catalysts, the actual trimerization mechanism appears to be a blend between the two types of mechanisms proposed thus far for the oligomerization of heterocumulenes with very different catalysts. In conclusion, this work contributes to a better understanding of the reactivity of arylisocyanates in the vicinity of late group 10 metal centers in low oxidation state and sheds some light on the detrimental self-poisoning processes observed during the reductive carbonylation of nitroaromatic substrates catalyzed by related catalysts in non-nucleophilic media.

PPAR-gamma2 Pro12Ala variant is associated with greater insulin sensitivity in childhood obesity.

Several genetic variants of peroxisome proliferator-activated receptor-gamma2 (PPAR-gamma2), a molecule known to be involved in transcription of target genes, have been identified. Pro12Ala, a missense mutation in exon 2 of the gene, is highly prevalent in Caucasian populations. Conflicting conclusions about the association between this mutation and complex traits such as obesity, insulin sensitivity, and T2DM have been reported. We have investigated the association of PPAR-gamma2 Pro12Ala polymorphism with measures of insulin sensitivity in a population of Italian obese children (n = 200; mean age, 10.38 +/- 2.8 y) in whom clinical and biochemical analyses were performed. To estimate the insulin sensitivity status, the homeostasis model assessment of insulin resistance (HOMA-IR) was calculated in all subjects. The effect of the Pro12Ala polymorphism on quantitative variables was tested using multiple linear regression analysis. The frequency of Ala carriers was 17%, similar to that reported in other adult Caucasian populations. The X12Ala (either Pro12Ala or Ala12Ala) genotype was associated with significantly lower fasting insulin levels compared with Pro/Pro (p = 0.008). Consistent with this finding, significantly lower HOMA-IR was observed in X12Ala carriers (p = 0.023). In conclusion, our observations demonstrate that the X12Ala variant is significantly associated with greater insulin sensitivity in childhood obesity. Because obesity is one of the most important risk factors for cardiovascular diseases and type 2 diabetes, obese children, who are presumably at a higher risk, may be protected from these diseases by the phenotypic effect of the Ala 12 allele on insulin resistance.

Synthesis and structural studies of binuclear platinum(II) complexes with a novel phosphorus-nitrogen-phosphorus ligand.

The new pyridinediphosphinite ligand PONOP (1) was synthesized in one step from 2,6-pyridinedimethanol and diphenylchlorophosphane. Reaction of 1 with PtCl(2)(PhCN)(2) led to the neutral homobimetallic complex [Pt(2)Cl(4)(PONOP)(2)] (2), where the benzonitriles have been substituted by the phosphorus atoms of 1. The X-ray structure of 2 revealed a metallamacrocycle where the pyridines remained free. Addition of 2 equiv of [Cu(MeCN)(4)](BF(4)) to 2 led to CuCl and to the binuclear dicationic complex [Pt(2)Cl(2)(PONOP)(2)](BF(4))(2) (3), where chloro ligands have been substituted by pyridine groups. Conversely, reaction of 3 with chloride anions gave back complex 2. Solid-state (X-ray) and solution (NMR) studies indicated that after the transformation of 2 into 3, the platinum centers were brought much closer and the pyridinediphosphinite ligand was stiffened. The methylene NMR protons of 3 were strongly deshielded, and the corresponding proton-phosphorus coupling constants followed a Karplus-type relationship.