Polysulfide Anions as Visible Light Photoredox Catalysts for Aryl Cross-Couplings.

Polysulfide anions are endowed with unique redox properties, attracting considerable attentions for their applications in alkali metals-sulfur batteries. However, the employment of these anionic species in redox catalysis for small molecule synthesis remains underdeveloped due to their moderate-poor electrochemical potential in the ground state, whereas some of them are characterized by photoabsorptions in visible spectral regions. Herein, we disclose the use of polysulfide anions as visible light photoredox catalysts for aryl cross-coupling reactions. The reaction design enables single-electron reduction of aryl halides upon the photoexcitation of tetrasulfide dianions (S42-). The resulting aryl radicals are engaged in (hetero)biaryl cross-coupling, borylation, and hydrogenation in a redox catalytic regime involving S4• -/S42- and S3• -/S32- redox couples.

Hydromagnesiation of 1,3-Enynes by Magnesium Hydride for Synthesis of Tri- and Tetra-substituted Allenes.

A protocol for regio-controlled hydromagnesiation of 1,3-enynes was developed using magnesium hydride that is generated in situ by solvothermal treatment of sodium hydride (NaH) and magnesium iodide (MgI2 ) in THF. The resulting allenylmagnesium species could be converted into tri- and tetra-substituted allenes by subsequent treatment with various carbon- and silicon-based electrophiles with the aid of CuCN as a catalyst.

Concerted Nucleophilic Aromatic Substitution Reactions.

Recent developments in experimental and computational chemistry have identified a rapidly growing class of nucleophilic aromatic substitutions that proceed by concerted (cSN Ar) rather than classical, two-step, SN Ar mechanisms. Whereas traditional SN Ar reactions require substantial activation of the aromatic ring by electron-withdrawing substituents, such activating groups are not mandatory in the concerted pathways.

Base-Induced Dehydrogenative and Dearomative Transformation of 1-Naphthylmethylamines to 1,4-Dihydronaphthalene-1-carbonitriles.

Solvothermal treatment of 1-naphthylmethylamine with potassium hydride (KH) or n-butyllithium (n-BuLi)-potassium t-butoxide (t-BuOK) in THF induces unusual two consecutive ß-hydride eliminations to form 1-naphthonitrile and KH. The freshly generated KH is hydridic enough to undergo dearomative hydride addition to the resultant 1-naphthonitrile regioselectively at the C4 position to afford α-cyano benzylic carbanion, which could be functionalized by a series of electrophiles, liberating the corresponding 1,4-dihydronaphthalene-1-carbonitriles having a quaternary carbon center.

Generation of organo-alkaline earth metal complexes from non-polar unsaturated molecules and their synthetic applications.

Organomagnesium compounds, represented by the Grignard reagents, are one of the most classical yet versatile carbanion species which have widely been utilized in synthetic chemistry. These reagents are typically prepared via oxidative addition of organic halides to magnesium metals, via halogen-magnesium exchange between halo(hetero)arenes and organomagnesium reagents or via deprotonative magnesiation of prefunctionalized (hetero)arenes. On the other hand, recent studies have demonstrated that the organo-alkaline earth metal complexes including those based on heavier alkaline earth metals such as calcium, strontium and barium could be generated from readily available non-polar unsaturated molecules such as alkenes, alkynes, 1,3-enynes and arenes through unique metallation processes. Nonetheless, the resulting organo-alkaline earth metal complexes could be further functionalized with a variety of electrophiles in various reaction modes. In particular, organocalcium, strontium and barium species have shown unprecedented reactivity in the downstream functionalization, which could not be observed in the reactivity of organomagnesium complexes. This perspective will focus on the newly emerging protocols for the generation of organo-alkaline earth metal complexes from non-polar unsaturated molecules and their applications in chemical synthesis and catalysis.

Stereo-controlled anti-hydromagnesiation of aryl alkynes by magnesium hydrides.

A concise protocol for anti-hydromagnesiation of aryl alkynes was established using 1 : 1 molar combination of sodium hydride (NaH) and magnesium iodide (MgI2) without the aid of any transition metal catalysts. The resulting alkenylmagnesium intermediates could be trapped with a series of electrophiles, thus providing facile accesses to stereochemically well-defined functionalized alkenes. Mechanistic studies by experimental and theoretical approaches imply that polar hydride addition from magnesium hydride (MgH2) is responsible for the process.

Evaluation of ferrocenyl phosphines as potent antimalarials targeting the digestive vacuole function of Plasmodium falciparum.

Owing to their lipophilic nature and chemical stability, ferrocene and its derivatives have been widely explored as antimicrobial agents, in combination with other active chemical 'war heads'. A prime example is ferroquine, an analogue of chloroquine obtained by covalently bonding ferrocene to 4-aminoquinoline, which possesses superior efficacy against multi-drug resistant malaria parasites. Herein, we explored the possibility of combining the ferrocenyl moiety with a phosphine unit and the subsequent inclusion of gold(i) to derive a molecular framework with demonstrated potential in inhibiting parasitic diseases. A library of 24 compounds consisting of 5 non-functionalized ferrocenyl enones and 19 ferrocenyl phosphine derivatives were synthesized, verified and tested against Plasmodium (P.) falciparum, which allowed us to identify compounds with low micromolar potency against both normal and chloroquine-resistant strains. Through flow cytometry combined with microscopic examination of Giemsa-stained thin smears, we observed that most of the active compounds interfered with trophozoite development as well as schizont maturation. The gold complex, namely G3, derived from the hydrophosphination of the terminal furan bearing an enone substrate showed the highest inhibitory potential. We demonstrate that G3 is affecting the parasite's metabolic processes as evident from the swollen digestive vacuole. Furthermore, G3 significantly affected heme de-toxification as determined through the ß-hematin assay, which caused apparent oxidative stress on parasites leading to death. Collectively, these results point out the potential of gold-conjugated ferrocenyl phosphine derivatives as antimalarials targeting the digestive vacuole function and metabolism of parasites.

Nucleophilic amination of methoxypyridines by a sodium hydride-iodide composite.

A new protocol for nucleophilic amination of methoxypyridines and their derivatives was developed using sodium hydride (NaH) in the presence of lithium iodide (LiI). The method offers a concise access to various aminopyridines which are potentially of medicinal interest.

Dearylation of arylphosphine oxides using a sodium hydride-iodide composite.

A new protocol for the dearylation of arylphosphine oxides was developed using sodium hydride (NaH) in the presence of lithium iodide (LiI). The transient sodium phosphinite could be functionalized with a range of electrophiles in a one-pot fashion.

Screening of ferrocenyl-phosphines identifies a gold-coordinated derivative as a novel anticancer agent for hematological malignancies.

The development of new organometallic compounds as anticancer agents is currently an active area of research. Here, we report the design, synthesis and characterization of a panel of 10 new ferrocenyl-phosphine derivatives (FD1-FD10) and the analysis of their anti-proliferative activities in hematolymphoid cells representing non-Hodgkin cutaneous T-cell lymphoma (CTCL). The gold-coordinated ferrocenyl-phosphine complex FD10 exhibited a significant and dose-dependent cytotoxicity in 4 different CTCL cell lines - HuT78, HH, MJ and MyLa. FD10 concentrations causing 50% cell growth inhibition (IC50) of HuT78, HH, MJ and MyLa cells at 24 h were recorded to be 5.55 ± 0.20, 7.80 ± 0.09, 3.16 ± 0.10 and 6.46 ± 0.24 µM respectively. Further mechanistic studies showed that FD10 induced apoptosis in CTCL cells by an intrinsic pathway mediated via the activation of caspase-3 and poly(ADP-ribose)polymerase. It suppressed the expression and activity of STAT3 oncoprotein in CTCL cells. FD10 caused robust G0/G1 phase cell cycle arrest and reduced the expression levels of Akt S473 phosphorylation and c-Myc, both are key cell cycle regulator proteins. Taken together, this study highlights anticancer properties of the ferrocenyl-phosphine gold organometallic complex FD10 and suggests that further development of this novel class of molecule may contribute to new drug discovery for certain hematolymphoid malignancies.