Influence of the cavity size of water-soluble cryptophanes on their binding properties for cesium and thallium cations.

The binding properties of water-soluble cryptophane 1 toward cesium and thallium cations, in basic solution, have recently been reported. In this Article, we show that water-soluble cryptophane-222 (2), cryptophane-223 (3), and cryptophane-233 (4), bearing zero, one, and two propylenedioxy linkers, respectively, also efficiently bind these two cations under similar experimental conditions. Their binding properties are thoroughly studied by (133)Cs and (205)Tl NMR spectroscopy, while the binding constants are determined by isothermal titration calorimetry (ITC) experiments under various experimental conditions. Complexation of cesium and thallium is also evidenced by electronic circular dichroism (ECD) using the enantiopure MM-2 compound. This study reveals that the cavity size of the cryptophane is not the main parameter to observe efficient binding. In contrast, the number of phenolate moieties surrounding the cryptophane backbone seems to be pivotal for the complexation of these two cations. These results are important in the field of detoxification.

Cationic cyclization of 2-alkenyl-1,3-dithiolanes: diastereoselective synthesis of trans-decalins.

An unprecedented and highly diastereoselective 6-endo-trig cyclization of 2-alkenyl-1,3-dithiolanes has been developed yielding trans-decalins, an important scaffold present in numerous di- and triterpenes. The novelty of this 6-endo-trig cyclization stands in the stepwise mechanism involving 2-alkenyl-1,3-dithiolane, acting as a novel latent initiator. It is suggested that the thioketal opens temporarily under the influence of TMSOTf, triggering the cationic 6-endo-trig cyclization, and closes after C-C bond formation and diastereoselective protonation to terminate the process. DFT calculations confirm this mechanistic proposal and provide a rationale for the observed diastereoselectivity. The reaction tolerates a wide range of functionalities and nucleophilic partners within the substrate. We have also shown that the one-pot 6-endo-trig cyclization followed by in situ 1,3-dithiolane deprotection afford directly the corresponding ketone. This improvement allowed the achievement of the shortest total synthesis of triptophenolide and the shortest formal synthesis of triptolide.

Diastereoselective formal total synthesis of (+/-)-triptolide via a novel cationic cyclization of 2-alkenyl-1,3-dithiolane.

A concise and diastereoselective formal total synthesis of triptolide, a natural product with a wide range of biological properties, is described. The key reaction is an unprecedented 6-endo-Trig cationic cyclization of a 2-alkenyl-1,3-dithiolane precursor induced by TMSOTf as Lewis acid.

Solvent-dependent oxidations of 5- and 6-azaindoles to trioxopyrrolopyridines and functionalised azaindoles.

A regioselective synthesis of 4,7-dimethoxy 5- and 6-azaindoles 2 has been achieved, based on the appropriate choice of ortho-directing or ortho-repulsing groups in the formylation of a pyridine ring. Studies on the regioselectivity of the formylation step and on the preparation of azidoacrylate intermediates 4 are described in this paper. The reactivity of the 5- and 6-azaindole structures towards BBr3-mediated selective monodemethylation and oxidative demethylation reactions were also investigated. The regioselectivity of the deprotection was confirmed using a chemical approach. Oxidation reactions were then carried out on either dimethoxy- or hydroxymethoxyazaindoles, in different solvents, using [bis(trifluoroacetoxy)iodo]benzene. In acetonitrile-water, trioxopyrrolopyridines 12 were obtained, whereas the formation of functionalised azaindoles 17 was observed in acetonitrile-methanol. The tautomeric structure of the trioxopyrrolopyridines was proved by X-ray diffraction analysis.