Ambient Moisture Accelerates Hydroamination Reactions of Vinylarenes with Alkali-Metal Amides under Air.

A straightforward alkali-metal-mediated hydroamination of styrenes using biorenewable 2-methyltetrahydrofuran as a solvent is reported. Refuting the conventional wisdom of the incompatibility of organolithium reagents with air and moisture, shown here is that the presence of moisture is key in favoring formation of the target phenethylamines over competing olefin polymerization products. The method is also compatible with sodium amides, with the latter showing excellent promise as highly efficient catalysts under inert atmosphere conditions.

Structural and Synthetic Insights into Pyridine Homocouplings Mediated by a ß-Diketiminato Magnesium Amide Complex.

The reaction of [(Dipp Nacnac)Mg(TMP)] (1) with 4-subtituted pyridines proceeds via sequential regioselective metallation and 1,2-addition to furnish a range of symmetric 4,4'-R2 -2,2'-bipyridines in good yield, representing a new entry into bipyridine synthesis. Interestingly, the reaction of 1 with 2-OMe-pyridine led to formation of asymmetric bipyridine 6, resulting from the C6-magnesiation of the heterocycle followed by a C-C coupling step by addition to the C2 position of a second, non-metallated molecule, and subsequent elimination of [Dipp NacnacMgOMe]2 (7). Synthesis combined with spectroscopic and structural analysis help rationalise the underlying processes resulting in the observed reactivity, and elucidate the key role that the sterically encumbered ß-diketiminate ligand plays in determining regioselectivity.

Magnesium-mediated arylation of amines via C-F bond activation of fluoroarenes.

A series of new Mg(ii) amides featuring a bulky ß-diketiminate backstop ligand, has been synthesised. These complexes are demonstrated to be excellent sources of nucleophilic amides that can participate in rapid C-F activation of several fluoroarenes at room temperature or using microwave assistance, leading to the installment of synthetically important C-N bonds via nucleophilic substitution.

Alkali metal and stoichiometric effects in intermolecular hydroamination catalysed by lithium, sodium and potassium magnesiates.

Main group bimetallic complexes, while being increasingly used in stoichiometric deprotonation and metal-halogen exchange reactions, have not yet made a significant impact in catalytic applications. This paper explores the ability of alkali metal magnesiates to catalyse the intermolecular hydroamination of alkynes and alkenes using sytrene and diphenylacetylene as principle setting model substrates. By systematically studying the role of the alkali-metal and the formulation of the heterobimetallic precatalyst, this study establishes higher order potassium magnesiate [(PMDETA)2K2Mg(CH2SiMe3)4] (7) as a highly effective system capable of catalysing hydroamination of styrene and diphenylacetylene with several amines while operating at room temperature. This high reactivity contrasts with the complete lack of catalytic ability of neutral Mg(CH2SiMe3)2, even when harsher reaction conditions are employed (24 h, 80 °C). A pronounced alkali metal effect is also uncovered proving that the alkali metal (Li, Na, or K) is not a mere spectating counterion. Through stoichiometric reactions, and structural and spectroscopic (DOSY NMR) investigations we shed some light on the potential reaction pathway as well as the constitution of key intermediates. This work suggests that the enhanced catalytic activity of 7 can be rationalised in terms of the superior nucleophilic power of the formally dianionic magnesiate {Mg(NR2)4}2- generated in situ during the hydroamination process, along with the ability of potassium to engage in π-interactions with the unsaturated organic substrate, enhancing its susceptibility towards a nucleophilic attack by the amide anion.

s-Block cooperative catalysis: alkali metal magnesiate-catalysed cyclisation of alkynols.

Mixed s-block metal organometallic reagents have been successfully utilised in the catalytic intramolecular hydroalkoxylation of alkynols. This success has been attributed to the unique manner in which these reagents can overcome the challenges of the reaction: namely OH activation and coordination to and then addition across a C[triple bond, length as m-dash]C bond. In order to optimise the reaction conditions and to garner vital catalytic system requirements, a series of alkali metal magnesiates were enlisted for the catalytic intramolecular hydroalkoxylation of 4-pentynol. In a prelude to the main investigation, the homometallic magnesium dialkyl reagent MgR2 (where R = CH2SiMe3) was utilised. This reagent was unsuccessful in cyclising the alcohol into 2-methylenetetrahydrofuran 2a or 5-methyl-2,3-dihydrofuran 2b, even in the presence of multidentate Lewis donor molecules such as N,N,N',N'',N''-pentamethyldiethylenetriamine (PMDETA). Alkali metal magnesiates MIMgR3 (when MI = Li, Na or K) performed the cyclisation unsatisfactorily both in the absence/presence of N,N,N',N'-tetramethylethylenediamine (TMEDA) or PMDETA. When higher-order magnesiates (i.e., MI 2MgR4) were employed, in general a marked increase in yield was observed for MI = Na or K; however, the reactions were still sluggish with long reaction times (22-36 h). A major improvement in the catalytic activity of the magnesiates was observed when the crown ether molecule 15-crown-5 was combined with sodium magnesiate Na2MgR4(TMEDA)2 furnishing yields of 87% with 2a : 2b ratios of 95 : 5 after 5 h. Similar high yields of 88% with 2a : 2b ratios of 90 : 10 after 3 h were obtained combining 18-crown-6 with potassium magnesiate K2MgR4(PMDETA)2. Having optimised these systems, substrate scope was examined to probe the range and robustness of 18-crown-6/K2MgR4(PMDETA)2 as a catalyst. A wide series of alkynols, including terminal and internal alkynes which contain a variety of potentially reactive functional groups, were cyclised. In comparison to previously reported monometallic systems, bimetallic 18-crown-6/K2MgR4(PMDETA)2 displays enhanced reactivity towards internal alkynol-cyclisation. Kinetic studies revealed an inhibition effect of substrate on the catalysts via adduct formation and requiring dissociation prior to the rate limiting cyclisation step.

Ligand-induced reactivity of ß-diketiminate magnesium complexes for regioselective functionalization of fluoroarenes via C-H or C-F bond activations.

Using ß-diketiminate Mg(ii) complexes containing either alkyl, aryl or amide groups, the regioselective functionalization of a wide range of fluoroarenes is accomplished but in uniquely different ways. Overcoming common limitations of traditional s-block bases, kinetically activated [(DippNacnac)Mg(TMP)] (1) deprotonates these molecules at room temperature, trapping sensitive fluoroaryl anions that can then engage in Negishi cross-coupling; whereas [(DippNacnac)Mg(R)THF] (R = nBu, Ph, benzofuryl) have proved to be effective reagents for C-F bond alkylation/arylation via pyridine directed C-F bond cleavage.

Regioselective magnesiation of N-heterocyclic molecules: securing insecure cyclic anions by a ß-diketiminate-magnesium clamp.

Using a specially designed magnesium metallating manifold, combining kinetically activated TMP amide base with a sterically amplified ß-diketiminate ligand, this study has established a new regioselective strategy for magnesiation of challenging N-heterocyclic molecules. The broad scope of the approach is illustrated through reactions of pyrazine, triazoles and substituted pyridines by isolation and structural elucidation of their magnesiated intermediates.

Seven-membered cycloplatinated complexes as a new family of anticancer agents. X-ray characterization and preliminary biological studies.

A series of seven-membered cyclometallated Pt(II) complexes containing a terdentate [C,N,N'] ligand (1a-1c and 2a-2c) have been developed as potential monofunctional DNA binding agents. By reactions of cis-[Pt(4-C(6)H(4)Me)(2)(µ-SEt(2))](2) or cis-[Pt(C(6)H(5))(2)(SMe(2))(2)] with imines 2-ClC(6)H(4)CHNCH(2)CH(2)NMe(2) (b) or 2-F,6-ClC(6)H(3)CH=NCH(2)CH(2)NMe(2) (c) the new compounds 1b, 1c and 2c were synthesized and characterized. Complex 1b and 1c were further characterized by X-ray crystallography. The cytotoxicity assessment of the seven-membered platinacycles 1 (1a-1c) and 2 (2a-2c) against a panel of human cancer cell lines (A549 lung, HCT116 colon, and MDA MB231 breast adenocarcinomas) revealed that the six cycloplatinated complexes exhibit a remarkable antiproliferative activity, even greater than cisplatin in the three human cancer cell lines. From a pharmacological point of view, platinacycles 1 (1a-1c) and 2 (2a-2c) may represent compounds for a new class of antitumor drugs. Electrophoretic DNA migration studies showed that all of them modify the DNA tertiary structure. Induction of S-G2/M arrest and apoptosis were also observed for one of the representative compounds (1c) of the series.