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[Image: see text] Investigation of the trans-fluorine effect on the hydrolysis rate of diethyl 2-fluorocyclopropane-1,1-dicarboxylate provides synthetic access to both diastereomers of the fluorocyclopropyl analog of cabozantinib, a c-Met and VEGFR-2 inhibitor used as a first-line treatment for thyroid cancer and as a second-line treatment for renal cell carcinoma. Despite some known potent examples, there are only a few drug molecules that contain fluorocyclopropane moieties. Herein, we present a case study in which the monofluoro analog of a known cyclopropane-containing drug molecule displays an improved in vitro profile compared to the parent nonfluorinated structure. The fluorocyclopropane moiety may offer valuable fine-tuning options for lead optimization in drug discovery.

A nuclear magnetic resonance (NMR) spectrometer is a key instrument in the organic synthesis laboratory for structure determination, reaction control, and compound purity analysis. In addition to qualitative analysis, the application of NMR for quantitative analysis (qNMR) is gaining popularity. qNMR allows for simple quantification of crude product mixtures, determination of reaction yields, and purity of organic compounds. The determination of NMR yield requires the addition of an internal standard to each sample. Herein, we report a method where CDCl

An investigation of the properties and reactivity of fluoromethylsulfonium salts resulted in the redesign of the reagents for fluoromethylene transfer chemistry. The model reaction, fluorocyclopropanation of nitrostyrene, turned out to be a suitable platform for the discovery of more streamlined fluoromethylene transfer reagents. The incorporation of halides on one aryl ring increased the reactivity, and 2,4-dimethyl substitution on the other aryl ring provided a balance between the reactivity/crystallinity of the reagent as well as the atom economy. The utility of new reagents was demonstrated by the development of an efficient fluorocyclopropanation protocol to access a range of monofluorinated cyclopropane derivatives.

Aryl substituted 2,2,2-trifluorodiazoethanes undergo rhodium(II)-catalysed insertion reactions with tin hydrides affording the corresponding α-(trifluoromethyl)benzyl stannanes. This reactivity contrasts with that of diazo esters which predominantly afford CH2 reduction products in the presence of tin hydrides. The first example of asymmetric insertion into tin hydrides using diazo compounds is also described. In addition, this system extends to asymmetric germanium hydride and silane insertion.

This study describes synthetic efforts towards the molecular Borromean link consisting of three unequal rings. The design and strategy involve step by step construction of a ruthenium(II) templated ring-in-ring complex doubly threaded with endocyclic ligands ready for the macrocyclization. The control over the topology is achieved by using specially designed directional building blocks based on 2,2′:6′,2′′-terpyridine. Preliminary macrocyclization attempts utilizing the copper-mediated Eglington reaction provide the mass spectrometric evidence consistent with the ruthenium(II) complex of the molecular Borromean link.

This work was supported by the Swiss National Science Foundation. A kinetically directed, stepwise approach towards molecular Borromean links enabled the isolation and structural characterization of synthetic intermediates along the way. Here we report the synthesis and crystal structures of three flexible macrocyclic intermediates and a new ring-in-ring complex, anchored together through ruthenium(ii) centers, which contains open terpyridine caps in the inner Ring II. Terpyridines circumvent the conformational cis/trans limitations of bipyridines and the new ring-in-ring complex forms tetrametallic complexes with Zn(ii), Pt(ii) and Ru(iii) metal ions. Analysis of the four macrocyclic structures provides a good foundation for the conformational flexibility in these complexes and demonstrates the robust applicability of the terpyridine design elements towards the engineered synthesis of ring-in-ring topologies. Publisher PDF

Octahedral metal complexes of tridentate 2,2′:6′,2′′-terpyridine (terpy) fused with five-membered furan rings mimic the topology of tetrahedral metal complexes of bidentate 5,5′-functionalized 2,2′-bipyridine (bipy). Herein, we report the robust synthesis of 2,6-bis(2-substituted-furo[2,3-c]pyridine-5-yl)pyridine based ligands to access a series of linear bilateral extended terpy derivatives. This molecular design of alternating five- and six-membered rings has been applied to extend the applicability of terpy as a building block in supramolecular chemistry. The complexation of 2,6-bis(2-substituted-furo[2,3-c]pyridine-5-yl)pyridine derivatives with metal ions preferring octahedral geometry (Fe2+, Ru2+, and Zn2+) gives molecular “crossings” and “corners”. Such design elements, functionalized with 4-pyridyl groups, allowed the construction of 3D and 2D heterometallic supramolecular networks containing Fe2+, Ag+ or Fe2+, Cu+ metal centers.