Enantioselective synthesis of α-secondary and α-tertiary piperazin-2-ones and piperazines by catalytic asymmetric allylic alkylation.

The asymmetric palladium-catalyzed decarboxylative allylic alkylation of differentially N-protected piperazin-2-ones allows the synthesis of a variety of highly enantioenriched tertiary piperazine-2-ones. Deprotection and reduction affords the corresponding tertiary piperazines, which can be employed for the synthesis of medicinally important analogues. The introduction of these chiral tertiary piperazines resulted in imatinib analogues which exhibited comparable antiproliferative activity to that of their corresponding imatinib counterparts.

Mechanical stability of bivalent transition metal complexes analyzed by single-molecule force spectroscopy.

Multivalent biomolecular interactions allow for a balanced interplay of mechanical stability and malleability, and nature makes widely use of it. For instance, systems of similar thermal stability may have very different rupture forces. Thus it is of paramount interest to study and understand the mechanical properties of multivalent systems through well-characterized model systems. We analyzed the rupture behavior of three different bivalent pyridine coordination complexes with Cu(2+) in aqueous environment by single-molecule force spectroscopy. Those complexes share the same supramolecular interaction leading to similar thermal off-rates in the range of 0.09 and 0.36 s(-1), compared to 1.7 s(-1) for the monovalent complex. On the other hand, the backbones exhibit different flexibility, and we determined a broad range of rupture lengths between 0.3 and 1.1 nm, with higher most-probable rupture forces for the stiffer backbones. Interestingly, the medium-flexible connection has the highest rupture forces, whereas the ligands with highest and lowest rigidity seem to be prone to consecutive bond rupture. The presented approach allows separating bond and backbone effects in multivalent model systems.

A practical two-step procedure for the preparation of enantiopure pyridines: Multicomponent reactions of alkoxyallenes, nitriles and carboxylic acids followed by a cyclocondensation reaction.

A practical approach to highly functionalized 4-hydroxypyridine derivatives with stereogenic side chains in the 2- and 6-positions is described. The presented two-step process utilizes a multicomponent reaction of alkoxyallenes, nitriles and carboxylic acids to provide ß-methoxy-ß-ketoenamides which are transformed into 4-hydroxypyridines in a subsequent cyclocondensation. The process shows broad substrate scope and leads to differentially substituted enantiopure pyridines in good to moderate yields. The preparation of diverse substituted lactic acid derived pyrid-4-yl nonaflates is described. Additional evidence for the postulated mechanism of the multicomponent reaction is presented.

A three-component synthesis of beta-alkoxy-beta-keto-enamides--flexible precursors for 4-hydroxypyridine derivatives and their palladium-catalysed reactions.

The flexible three-component reaction of lithiated alkoxyallenes with nitriles and carboxylic acids provided a series of highly functionalised beta-alkoxy-beta-ketoenamide derivatives. Upon base induced cyclisation and conversion to 4-pyridyl nonaflates various palladium-catalysed coupling reactions could be employed. The efficacy of this approach to functionalised pyridine derivatives was demonstrated by a fairly short route to a key intermediate suitable for a Glenvastatin synthesis. After Sonogashira couplings of alkynes with 4-pyridyl nonaflates subsequent cyclisations led to highly fluorescent [2,3c]furopyridine derivatives, whereas Suzuki reactions afforded 4-pyridyl stilbenes and by photocyclisation a highly substituted benzoisoquinoline derivative.

One-pot synthesis of benzofurans via palladium-catalyzed enolate arylation with o-bromophenols.

A one-pot synthesis of benzofurans which utilizes a palladium-catalyzed enolate arylation is described. The process demonstrates broad substrate scope and provides differentially substituted benzofurans in moderate to excellent yields. The utility of the method is further demonstrated by the synthesis of the natural product eupomatenoid 6 in three steps.

An unusual barium olefin complex.

Reacting [(eta5-C5Me5)In] in the presence of [(eta5-C5Me5)2Ba] results in the C-H activation of the barocene ligand framework. A barium metallocene with an intramolecular barium-olefin bond was formed.