Deprotonation of chloropyridines using lithium magnesates

4-Chloropyridine was deprotonated on treatment with 1/3 equiv of the highly coordinated magnesate Bu₃(TMP)MgLi₂ in THF at −10 °C, as evidenced by trapping with I₂. The use of Bu(TMP)₂MgLi in Et₂O allowed the reaction of 2-chloropyridine, giving the 3-functionalized derivative as the main product. Mixtures of 3- and 4-functionalized derivatives were obtained when 2,6-dichloropyridine was involved in the reaction. Performing the reaction on 3-chloropyridine with lithium magnesates in THF, either the 4,4′-dimer or the 4-iodo derivative was formed after quenching by I₂, the former using 1/3 equiv of Bu₂(TMP)MgLi and the latter using 1 equiv of (TMP)₃MgLi. Similar results were observed with 3,5-dichloropyridine, 2,5-dichloropyridine and 3-chloro-2-fluoropyridine. 1,2-Migration of the lithium arylmagnesate formed by deprotonation was proposed to justify the dimers formation.     

Deprotonation of fluoro aromatics using lithium magnesates

3-Fluoropyridine was deprotonated on treatment with 1/3 equiv of Bu₃MgLi in THF at −10 °C. The lithium arylmagnesate formed was either trapped with electrophiles or involved in a palladium-catalyzed cross-coupling reaction with 2-bromopyridine. The use of a less nucleophilic lithium-magnesium-dialkylamide, (TMP)₃MgLi, allowed the reaction of 3-fluoroquinoline, giving the 2,2′-dimeric derivative. 2-Fluoropyridine and 2,6-difluoropyridine were deprotonated using 1/3 equiv of the highly coordinated magnesate Bu₄MgLi₂ in THF at −10 °C in the presence of a substoichiometric amount of 2,2,6,6-tetramethylpiperidine. 1,3-Difluorobenzene reacted similarly when treated with Bu₃MgLi; the reactivity of the base proved to be enhanced by the presence of TMEDA.     

Deprotonation of furans using lithium magnesates

Furan was deprotonated on treatment with 1/3 equiv of Bu₃MgLi in THF at rt. The lithium arylmagnesate formed was either trapped with electrophiles or involved in a palladium-catalyzed cross-coupling reaction with 2-bromopyridine. The highly coordinated magnesate Bu₄MgLi₂ (1/3 equiv) proved to be a better deprotonating agent than Bu₃MgLi; the monitoring of the reaction using NMR spectroscopy showed that the deprotonation of furan at rt required 2 h whereas the subsequent electrophilic trapping was instantaneous. The method was extended to benzofuran, allowing its functionalization at C2 in high yields. The deprotonation of 2-methylfuran and lithium furfurylalkoxide at C5 turned out to be difficult, requiring either long reaction times or higher temperatures.     

Sulfone–Metal Exchange and Alkylation of Sulfonylnitriles

The first general sulfone–metal exchange is described. Treating substituted 2‐pyridylsulfonylacetonitriles with either BuLi or Bu₃MgLi generates metalated nitriles that efficiently intercept a variety of electrophiles to afford quaternary nitriles. The 2‐pyridylsulfone is critical for the sulfone–metal exchange because chelation anchors the organometallic proximal to the electrophilic, tetrasubstituted sulfone to override complex‐induced deprotonation. Alkylating commercial 2‐pyridinesulfonylacetonitrile with mild bases, either K₂CO₃ or DBU, and subsequent sulfone–metal exchange and alkylation rapidly assembles quaternary nitriles by three alkylations, only one of which requires an organometallic reagent.     

Sulfone–Metal Exchange and Alkylation of Sulfonylnitriles

The first general sulfone–metal exchange is described. Treating substituted 2-pyridylsulfonylacetonitriles with either BuLi or Bu₃MgLi generates metalated nitriles that efficiently intercept a variety of electrophiles to afford quaternary nitriles. The 2-pyridylsulfone is critical for the sulfone–metal exchange because chelation anchors the organometallic proximal to the electrophilic, tetrasubstituted sulfone to override complex-induced deprotonation. Alkylating commercial 2-pyridinesulfonylacetonitrile with mild bases, either K₂CO₃ or DBU, and subsequent sulfone–metal exchange and alkylation rapidly assembles quaternary nitriles by three alkylations, only one of which requires an organometallic reagent.     

Tributylmagnesium ate complex-mediated bromine-magnesium exchange of bromoquinolines: a convenient access to functionalized quinolines

2-, 3- and 4-bromoquinolines were converted to the corresponding lithium tri(quinolyl)magnesates at −10°C by treatment with Bu₃MgLi in THF or toluene. The resulting organomagnesium derivatives were quenched by various electrophiles to afford functionalized quinolines.     

Synthesis and reactivity of lithium tri(quinolinyl)magnesates

2-, 3- and 4-Bromoquinolines were converted to the corresponding lithium tri(quinolinyl)magnesates at −10°C when exposed to Bu₃MgLi in THF. The resulting organomagnesium derivatives were quenched with various electrophiles or involved in metal-catalyzed coupling reactions with heteroaryl halides to afford functionalized quinolines.     

First cross-coupling reactions of arylmagnesates: a convenient access to heteroarylquinolines

2-, 3- and 4-Bromoquinolines were converted to the corresponding lithium tri(quinolyl)magnesates at −10°C on treatment with Bu₃MgLi in THF. The resulting organomagnesium derivatives were involved in catalyzed cross-coupling reactions with heteroaryl bromides and chlorides to afford functionalized quinolines.     

Controllable Hydrolysis Performance of MgLi Alloys and Their Hydrides

Theoretically, the hydrolysis of MgLi and MgH₂−LiH can produce 9.6 and 17.5 wt.% hydrogen (water is not included in the calculation), respectively. The ball-milling method is commonly used to refine the particle size and thus may improve hydrolysis kinetics. However, Mg and Li will be easily agglomerated, which means that direct ball-milling could not refine MgLi. In this work, we introduced 10 wt.% expanded graphite into the ball-milling process to synthesize refined MgLi alloy samples. Further studies showed that MgLi-10 wt.% expanded graphite can produce 966 mL/g hydrogen within 3 min in 0.5 M MgCl₂ solution. The MgLi hydrides were synthesized by reactive ball milling under 3 MPa H₂ and their hydrolysis performance was investigated. Moreover, the sawed powder was milled in 3 MPa H₂ for 6 h and then hydrogenated in 3 MPa H₂ at 380 °C; it can produce 1542 and 1773 mL/g (15.8 wt.%) hydrogen in 5 and 30 min with mild kinetics, respectively, and the activation energy of the hydrolysis reaction is 24.6 kJ/mol in 1 M MgCl₂ solution. The findings here open a new avenue to the development of refined MgLi alloys and hydrides for hydrogen generation through a controllable hydrolysis process.     

Reductive allylation of 1H-pyridine-2-(thio)ones by means of the novel lithium allyldibutylmagnesate reagent

A new, highly efficient allylation reagent—lithium allyldibutylmagnesate (allylBu₂MgLi)—was obtained by mixing allyl-magnesium chloride (1 equiv) and n-BuLi (2 equiv). N-Lithiated and N-methyl substituted 1H-pyridine-2-thiones and -ones were successfully and regioselectively allylated by treatment with allylBu₂MgLi yielding 6-allyl-3,6-dihydro-1H-pyridine-2-(thio)ones and 4-allyl-3,4-di-hydro-1H-pyridine-2-(thio)ones. The latter were formed by a 3,3-sigmatropic Cope rearrangement of the former.     

Deprotonation of thiophenes using lithium magnesates

Thiophene was regioselectively deprotonated at C2 on treatment with 1/3 equiv of Bu₃MgLi in THF at room temperature. The lithium arylmagnesate formed was either trapped with electrophiles or cross-coupled in a ‘one-pot’ procedure with aryl halides under palladium catalysis. 2-Chlorothiophene and 2-methoxythiophene were similarly deprotonated at C5 under the same reaction conditions. The enhancement of the reactivity of the base using TMEDA was evidenced using ¹H NMR spectroscopy.     

Direct α‐Siladifluoromethylation of Lithium Enolates with Ruppert‐Prakash Reagent via CF Bond Activation

The direct α‐siladifluoromethylation of lithium enolates with the Ruppert–Prakash reagent (CF₃TMS) is shown to construct the tertiary and quaternary carbon centers. The Ruppert–Prakash reagent, which is versatile for various trifluoromethylation as a trifluoromethyl anion (CF₃^?) equivalent, can be employed as a siladifluoromethyl cation (TMSCF₂⁺) equivalent by C?F bond activation due to the strong interaction between lithium and fluorine atoms.     

XPS and SIMS Examination of Alumina Fibres Affected with Mg and MgLi Melt

 Fibre/matrix interfaces in δ-Al₂O₃/Mg8Li and δ-Al₂O₃/Mg composites have been investigated using XPS and SIMS analysis of extracted δ-Al₂O₃ fibres in context with previous XRD observations. Results obtained indicate that in MgLi based composites lithium enters preferentially the interfacial redox reactions producing Li⁺ ions that occupy vacant cation positions in the defect δ-Al₂O₃ lattice which results in a strong fibre/matrix interfacial bond. On the other hand, in Mg matrix composites the magnesium oxide appears to be the final reaction product that does not enter the solid state reaction with adjacent δ-Al₂O₃ fibre during the melt infiltration process, so that only relatively weak interfacial bond is created.     

Selective halogen-magnesium exchange reaction via organomagnesium ate complex

Halogen-magnesium exchange of various aryl halides is achieved with a magnesium ate complex at low temperatures. Tributylmagnesate (nBu3MgLi) induces facile iodine-magnesium exchange at -78 degrees C. Dibutylisopropylmagnesate (iPr(n)Bu2MgLi) is more reactive than nBu3MgLi, and this reagent accomplishes selective bromine-magnesium exchange at -78 degrees C. This procedure is utilized for the preparation of various polyfunctionalized arylmagnesium species. The exchange of alkenyl halides using this method proceeds with retention of configuration of the double bond.     

New Preparation Methodology of Functionalized Picolines

Under the organomagnesium complex n‐Bu₂CH₃MgLi conditions, picoline compounds provide a new entry to a broad range of polyfunctional picoline derivatives, after reaction with various electrophiles.     

Schlenk's Legacy—Methyllithium Put under Close Scrutiny

Commercially available stock solutions of organolithium reagents are well-implemented tools in organic and organometallic chemistry. However, such solutions are inherently contaminated with lithium halide salts, which can complicate certain synthesis protocols and purification processes. Here, we report the isolation of chloride-free methyllithium employing K[N(SiMe₃)₂] as a halide-trapping reagent. The influence of distinct LiCl contaminations on the ⁷Li-NMR chemical shift is examined and their quantification demonstrated. The structural parameters of new chloride-free monomeric methyllithium complex [(Me₃TACN)LiCH₃], ligated by an azacrown ether, are assessed by comparison with a halide-contaminated variant and monomeric lithium chloride [(Me₃TACN)LiCl], further emphasizing the effect of halide impurities.     

Defect structures in the brannerite-type vanadates: VIII. Synthesis of the Mg1−yLiyV2−yMoyO6 and Mg1−x−yØxLiyV2−2x−yMo2x+yO6 solid solutions: Effect of strengthening the crystal lattice by substitution of monovalent ion for bivalent ion

It is shown that MgV₂O₆ and LiVMoO₆, both of the brannerite-type structure, exhibit miscibility in the entire composition range resulting in the formation of MgLi = Mg_1−yLi_yV_2−yMo_yO₆ solid solutions. For y > 0.5 significant capacity of the MgLi matrix to the excess Mo⁶⁺ cations compensated by cation vacancies Ø appears and MgLiØ = Mg_1−x−yØ_xLi_yV_2−2x−yMo_2x+yO₆ solutions become stable. Pronounced negative deviations from Vegard's law are simultaneously observed for MgLi solid solutions. An unusual phenomenon is thus observed: monovalent cation (Li⁺) substituted for bivalent cation (Mg²⁺) strengthens the brannerite-type lattice and increases its toleration to cation vacancies. A similar effect has recently been observed for ZnLi and ZnLiØ solid solutions (K. Mocała and J. Ziółkowski, J. Solid State Chem. 71, 426 (1987)); the effect is absent, however, in the case of MnLi and MnLiØ (J. Ziółkowski, K. Krupa, and K. Mocała, J. Solid State Chem. 48, 376 (1983)). Some speculations concerning this effect and some predictions are offered. X-ray data are listed for MgLi solid solutions of various compositions.     

Enantioselective Multicomponent Synthesis of Fused 6–5 Bicyclic 2‐Butenolides by a Cascade Heterobicyclisation Process

The successive coupling of an alkoxy(aryl/heteroaryl)carbene complex of chromium with either a ketone or an imide lithium enolate and then a 3‐substituted (H, TMS, PhCH₂, PhCH₂CH₂, Me) propargylic organomagnesium reagent has afforded novel hydroxy‐substituted bicyclic [4.3.0]‐γ‐alkylidene‐2‐butenolides with three modular points that has allowed the efficient introduction of molecular complexity, including a homopropargylic alcohol core. The selective formation of these five‐ or six‐component heterobicyclisation products is the result of the regioselective integration of the Grignard reagent as a propargyl fragment followed by a cascade CO/alkyne/CO insertion, ketene trapping and elimination sequence. By using lithium enolates of chiral N‐acetyl‐2‐oxazolidinones and the corresponding propargylic organocerium reagents, both enantiomers of these bicyclic heterocycles were efficiently prepared with very high enantiomeric purity. Architecturally, these fused bicyclic butenolides are characterised by a highly unsaturated and oxygenated core and they exhibit strong blue fluorescence in solution.     

Intramolecular Benzyne–Phenolate [4+2] Cycloadditions

An intramolecular benzyne–phenolate [4+2] cycloaddition is reported. Benzyne precursors, having vicinal halogen‐sulfonate functionalities, linked with a phenol(ate) by various tether groups undergo efficient intramolecular [4+2] cycloaddition by treatment with either Ph₃MgLi or nBuLi for halogen–metal exchange to form various benzobarrelenes.     

Synthesis of CF<Subscript>3</Subscript>-substituted 1,2,3,4-tetrahydroisoquinolines and 1,2,3,6-tetrahydropyridines

A three-step method for the preparation of CF₃-substituted 1,2,3,4-tetrahydroisoquino-lines and 1,2,3,6-tetrahydropyridines has been suggested. The first step includes alkylation of isoquinoline or 4-methylpyridine at the nitrogen atom with the formation of salts, which are involved into the reaction with Grignard reagent or lithium triethylborohydride to give enamines. The enamines undergo nucleophilic trifluoromethylation upon the action of Me₃SiCF₃ under acidic conditions.