A Phosphanyl Phosphagermene and its Reactivity.

Reaction of a nucleophilic germylene Ge[CH(SiMe3)2]2 with the phosphanyl phosphaketene [{(H2C)(NDipp)}2P]PCO induces decarbonylation to form a phosphanyl phosphagermene [{(H2C)(NDipp)}2P]P=Ge[CH(SiMe3)2]2 (1; Dipp = 2,6-diisopropyl-phenyl). Addition of CO2 or MeCN to 1 results in [3+2]-cycloaddition reactions to afford five-membered heterocycles. This mode of reactivity is reminiscent of that observed for frustrated Lewis pairs, with the pendant phosphanyl group acting as a base and the germanium center as a Lewis acid. Contrastingly, 1,2-addition across the P=Ge bond was observed when using ammonia, small primary amines (NH2nPr, NH2iPr), or metal complexes (e.g. Au(PPh3)Cl and ZnEt2). These latter reactions allow for the one-step synthesis of metal phosphide complexes.

Formation, Reactivity and Decomposition of Aryl Phospha-Enolates.

Two lithium phospha-enolates [RP=C(Sii Pr3 )OLi]2 were prepared by reaction of triisopropyl silyl phosphaethynolate, i Pr3 SiPCO, with aryl lithium reagents LiR (R=Mes: 1,3,5-trimethyl phenyl; or Mes*: 1,3,5,-tri-tertbutyl phenyl). Monomer/dimer aggregation of the enolates can be modulated by addition of 12-crown-4. Substitution of lithium for a heavier alkali metal was achieved through initial formation of a silyl enol ether, followed by reaction with KOt Bu to form the corresponding potassium phospha-enolate [MesP=C(Sii Pr3 )OK]2 . On addition of water, the enolates are protonated to afford RP=C(Sii Pr3 )(OH). For the sterically less demanding system (R=Mes), this phospha-enol rapidly tautomerises to the corresponding acyl phosphine MesP(H)C(Sii Pr3 )(O), which on heating extrudes CO. In contrast, bulkier phospha-enol (R=Mes*) is stable to rearrangement at room temperature and thermally decomposes to RH and i Pr3 SiPCO.

A Cyaphide Transfer Reagent.

The cyanide ion plays a key role in a number of industrially relevant chemical processes, such as the extraction of gold and silver from low grade ores. Metal cyanide compounds were arguably some of the earliest coordination complexes studied and can be traced back to the serendipitous discovery of Prussian blue by Diesbach in 1706. By contrast, heavier cyanide analogues, such as the cyaphide ion, C≡P-, are virtually unexplored despite the enormous potential of such ions as ligands in coordination compounds and extended solids. This is ultimately due to the lack of a suitable synthesis of cyaphide salts. Herein we report the synthesis and isolation of several magnesium-cyaphido complexes by reduction of iPr3SiOCP with a magnesium(I) reagent. By analogy with Grignard reagents, these compounds can be used for the incorporation of the cyaphide ion into the coordination sphere of metals using a simple salt-metathesis protocol.

A Structured Approach To Cope with Impurities during Industrial Crystallization Development.

The perfect separation with optimal productivity, yield, and purity is very difficult to achieve. Despite its high selectivity, in crystallization unwanted impurities routinely contaminate a crystallization product. Awareness of the mechanism by which the impurity incorporates is key to understanding how to achieve crystals of higher purity. Here, we present a general workflow which can rapidly identify the mechanism of impurity incorporation responsible for poor impurity rejection during a crystallization. A series of four general experiments using standard laboratory instrumentation is required for successful discrimination between incorporation mechanisms. The workflow is demonstrated using four examples of active pharmaceutical ingredients contaminated with structurally related organic impurities. Application of this workflow allows a targeted problem-solving approach to the management of impurities during industrial crystallization development, while also decreasing resources expended on process development.

The challenges of diagnosis and management of Gitelman syndrome.

Gitelman syndrome is an inherited tubulopathy characterized by renal salt wasting from the distal convoluted tubule. Defects in the sodium chloride cotransporter (encoded by SLC12A3) underlie this autosomal recessive condition. This article focuses on the specific challenges of diagnosing and treating Gitelman syndrome, with use of an illustrative case report. Symptoms relate to decreased serum potassium and magnesium levels, which include muscle weakness, tetany, fatigue and palpitations. Sudden cardiac deaths have been reported. Making a diagnosis may be difficult given its rarity but is important. A knowledge of the serum and urine biochemical picture is vital to distinguish it from a broad differential diagnosis, and application of genetic testing can resolve difficult cases. There is a group of Gitelman syndrome heterozygous carriers that experience symptoms and electrolyte disturbance and these patients should be managed in a similar way, though here genetic investigations become key in securing a difficult diagnosis. Potassium and magnesium replacement is the cornerstone of treatment, though practically this can be hard for patients to manage and often does not fully relieve symptoms even when serum levels are normalized. Challenges arise due to the lack of randomized controlled trials focussing on treatment of this rare disease; hence, clinicians endorse strategies in line with correction of the underlying pathophysiology such as sodium loading or pharmacological treatments, which seem to help some patients. Focussed dietary advice and knowing the best tolerated preparations of potassium and magnesium medications are useful tools for the physician, as well as an awareness of the specific burdens that this patient group face in order to signpost appropriate support.

Aluminium-mediated carbon-carbon coupling of an isonitrile.

Cp*Al reacts with diphenylacetylene to form a Cp*-substituted 1,4-dialuminacyclohexene. The dialuminacyclohexene reacts with four equivalents of an isonitrile to couple the terminal carbon atoms, forming 6 new carbon-carbon bonds and resulting in a zwitterionic diamide ligand which contains a carbocationic backbone.

Ligand coordination modulates reductive elimination from aluminium(iii).

Oxidative addition of inert bonds at low-valent main-group centres is becoming a major class of reactivity for these species. The reverse reaction, reductive elimination, is possible in some cases but far rarer. Here, we present a mechanistic study of reductive elimination from Al(iii) centres and unravel ligand effects in this process. Experimentally determined activation and thermodynamic parameters for the reductive elimination of Cp*H from Cp*2AlH are reported, and this reaction is found to be inhibited by the addition of Lewis bases. We find that C-H oxidative addition at Al(i) centres proceeds by initial protonation at the low-valent centre.