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.     

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.     

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.     

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.     

New Gilman-type lithium cuprate from a copper(II) salt: synthesis and deprotonative cupration of aromatics

Deprotonative cupration of aromatics including heterocycles (anisole, 1,4-dimethoxybenzene, thiophene, furan, 2-fluoropyridine, 2-chloropyridine, 2-bromopyridine, and 2,4-dimethoxypyrimidine) was realized in tetrahydrofuran at room temperature using the Gilman-type amido-cuprate (TMP)₂CuLi in situ prepared from CuCl₂·TMEDA through successive addition of 1 equiv of butyllithium and 2 equiv of LiTMP. The intermediate lithium (hetero)arylcuprates were evidenced by trapping with iodine, allyl bromide, methyl iodide, and benzoyl chlorides, the latter giving the best results. Symmetrical dimers were also prepared from lithium azine and diazine cuprates using nitrobenzene as an oxidative agent.     

σ-Bonded organometallic derivatives of yttrium(III) and thulium(III): An unusual ligand coupling reaction mediated by thulium(III)

The reaction between LnI₃(THF)_3.5 and 2 equiv. of {(Me₃Si)₂(Me₂MeOSi)C}K (1) in THF at room temperature yields only the mono-substituted products {(Me₃Si)₂(Me₂MeOSi)C}LnI₂(THF)₂ [Ln = Y (5), Tm (6)]; under more forcing conditions decomposition occurs. In contrast, the metathesis reaction between TmI₃(THF)_3.5 and 2 equiv. of the lithium iodide-containing salt {(Me₃Si)₂(Me₂MeOSi)C}K(LiI)_x yields the highly unusual separated ion pair complex [[{(Me₃Si)₂C(SiMe₂)}₂O]TmI₂{Li(THF)₃}₂][[{(Me₃Si)₂C(SiMe₂)}₂O]TmI₂] (8). The dianionic ligand in 8 is derived from the coupling of 2 equiv. of (Me₃Si)₂(Me₂MeOSi)C⁻, accompanied by the formal elimination of Me₂O. The structures of compounds 5, 6, and 8 have been determined by X-ray crystallography; compound 8 crystallizes as an unusual ion pair, the cation and anion of which differ only in the inclusion of 2 equiv. of Li(THF)₃ in the former, bridged to thulium by iodide ions.     

A simple one-step protocol for the olefination of vinylogous formamides

Vinylogous formamides--5-formyluracils and 4-formylpyrazoles-undergo smooth olefination in THF in the presence of indium metal (0.8 equiv) and BF₃·OEt₂ (1 equiv) and allyl bromide (1 equiv) to provide the respective diene-substituted heterocycles in a single step     

Synthesis of a tin-functionalized cyclopentadiene derivative

A 3-tert-butyl-1-(stannylpropyl)-functionalized cyclopentadienyl ligand precursor 6 is readily available in 64% overall yield from allylic alcohol 1 by a three-step reaction sequence including Pd-catalyzed hydrostannylation with Ph₃SnH. Treatment with FeCl₂ and ZrCl₄ · 2THF afforded corresponding ferrocene and zirconocene derivatives. Transmetallation of Sn-Ph with Li-Bu was observed under these reaction conditions by using BuLi as a base.     

Aliphatic organolithiums by fluorine-lithium exchange: n-octyllithium

The reaction of 1-fluorooctane (1) with an excess of lithium powder (4-10 equiv.) and DTBB (2-4 equiv.) in THP at 0°C for 5 min gives a solution of the corresponding 1-octyllithium (2), which reacts then with different electrophiles at 0°C (D₂O, MeSiCl, Bu^tCHO, Et₂CO), or −78°C [ClCO₂Me, (PhCH₂S)₂] or −40°C (CO₂) to room temperature to give, after hydrolysis, the expected products (3). The same process applied to 2-fluorooctane gives mainly octane as reaction product, independently on the electrophile used, resulting from a proton abstraction by 2-lithiooctane formed from the reaction medium before addition of the electrophilic reagent.     

Reactions of 1,2-catechol with Bu3M (M = Ga, In). Structures of intermediate products

Reactions of 1,2-catechol with ^tBu₃M (M = Ga, In) have been studied. Trinuclear compounds [^tBu₅M₃(OC₆H₄O)₂] [M = Ga (1), M = In (2)] were synthesised in the reaction of 2 equiv. of C₆H₄(OH)₂ with 3 equiv. of ^tBu₃M in refluxing solvents. At room temperature the reaction of 1,2-catechol with ^tBu₃In in Et₂O leads to the formation of a binuclear complex [^tBu₄In₂(OC₆H₄OH)₂ · 2Et₂O] (3) possessing a four-membered In₂O₂ core and two unreacted hydroxyl groups. The same reaction carried out in a non-coordinating solvent (CH₂Cl₂) results in formation a compound [^tBu₃In₂(OC₆H₄O)(OC₆H₄OH)] (4), which undergoes a reaction with ^tBu₃In to yield the product 2. Moreover two intermediate isomeric products 5 and 6 of formula [^tBu₃Ga₂(OC₆H₄O)(OC₆H₄OH)] were isolated from the post-reaction mixture of 1,2-catechol with ^tBu₃Ga. The compound 6 possessing a different coordination of gallium atoms than 5 is a result of the intramolecular rearrangement of the compound 5 to decrease the steric repultion between ligands. Compounds 3 and 6 were structurally characterised. According to the structure of intermediate products 3-6 a reaction pathway of 1,2-catechols with group 13 metal trialkyls was proposed.     

gem-Difluoropropargylation of aldehydes using cat. In/Zn in aqueous media

Zn (0.9 equiv) in combination with catalytic amounts of In (0.1 equiv) and I₂ (0.1 equiv) was found to effect the reaction of several difluoropropargyl bromide derivatives with aldehydes to produce gem-difluorohomopropargyl alcohols in aqueous media under conditions suitable for large scale applications.     

A simple method for the oxidation of α-amino acid esters to α-oximino esters

Magnesium bis(monoperoxyphthalate) hexahydrate (MMPP) was found to be an effective reagent for the oxidation of various α-amino acid esters to the corresponding α-oximino acid esters. This transformation could be completed under mild conditions within 2.5 h using 1.1 equiv of MMPP in THF. Clean oximino esters were obtained after quenching and extracting the reaction from sodium thiosulfate solution. The O-phosphorylated derivative of 2-oximinoglutarate exhibited slow binding inhibitory potency for the metallopeptidase prostate-specific membrane antigen (PSMA) with an IC₅₀ value of 58 nM.     

Kinetics and mechanism of the oxidation of 2,3,6-trimethylphenol with hydrogen peroxide in the presence of Ti-monosubstituted polyoxometalates

The product composition and reaction kinetics are reported for 2,3,6-trimethylphenol (TMP) oxidation with hydrogen peroxide in acetonitrile catalyzed by a Ti-monosubstituted polyoxometalate (Ti-POM) with a Keggin structure ([Bu₄N]₄[PTi(OMe)W₁₁O₃₉]) and for the stoichiometric reaction between TMP and the peroxo complex [Bu₄N]₄[HPTi(O)₂W₁₁O₃₉] (I). The main products of the stoichiometric reaction are 2,3,5-trimethyl-1,4-benzoquinone (TMBQ) and 2,2′,3,3′,6,6′-hexamethyl-4,4′-biphenol (BP). The TMBQ yield increases as the TMP/I molar ratio is decreased. The catalytic reaction is first-order with respect to H₂O₂ and the catalyst and has a variable order (1-0) with respect to TMP. The rate of the reaction increases as the water concentration in the reaction mixture is raised. The stoichiometric reaction is first-order with respect to peroxo complex I and has a variable order (1-0) with respect to TMP. There is no kinetic isotope effect for this reaction (k _ArOH/k _ArOD = 1). A TMP oxidation mechanism is suggested, which includes the coordination of a TMP molecule and peroxide on a Ti site of the catalyst with the formation of a reactive intermediate. The one-electron oxidation of TMP in this intermediate yields a phenoxyl radical. The subsequent conversions of these ArO^° radicals yield the reaction products.     

Bridged bis(amidinate) lanthanide complexes: Synthesis,molecular structure and reactivity

The yttrium chloride with the bridged bis(amidinate) L (L = Me₃SiNC(Ph)N(CH₂)₃NC(Ph)NSiMe₃) LYCl(DME) (2) was synthesized and structurally characterized. Treatment of LLnCl(sol)_x (Ln = Yb, sol = THF, x = 2 1; Ln = Y, sol = DME, x = 1 2) with the dilithium salt Li₂L(THF)_0.5 afforded the novel bimetallic lanthanide complexes supported by three ligands, Ln₂(μ₂-L)₃ · DME (Ln = Yb 3, Y 4; DME = dimethylether), instead of the designed complex LLn(μ₂-L)LnL via the ligand redistribution reaction. Complexes 3 and 4 were fully characterized including X-ray analysis and ¹H NMR spectrum for 4. Reaction of LnCl₃ (Ln = Yb, Y) with 2 equiv. of Li₂L(THF)_0.5 gave the anionic complexes [Li(DME)₃][L₂Ln] (Ln = Yb 5, Y 6), which were confirmed by a crystal structure determination. The further study indicated that complexes 3 and 4 can also be synthesized by reaction of LnCl₃ (Ln = Yb, Y) with 1.5 equiv. of Li₂L(THF)_0.5 or reaction of 1 and 2 with anionic complexes 5 and 6. Complexes 3, 4, 5 and 6 were found to be high active catalysts for ring-opening polymerization of ε-caprolactone (CL).     

Synthesis and molecular structures of lanthanocene amide complexes and their catalytic activity for addition of amines to nitriles

Reaction of (CH₃C₅H₄)₂LnCl(THF) with NaNHAr in a 1:1 molar ratio in THF afforded the amide complexes (CH₃C₅H₄)₂LnNHAr(THF) [(Ar = 2,6-Me₂C₆H_3, Ln = Yb (I), Y (III); Ar = 2,6-ⁱPr₂C₆H₃, Ln = Yb (II)]. X-ray crystal structure determination revealed that complexes I-III are isostructural. The central metal in each complex coordinated to two methylcyclopentadienyl groups, one amide group and one oxygen atom from THF to form a distorted tetrahedron. Complexes I-III and a known complex (CH₃C₅H₄)₂YbNⁱPr₂(THF) IV all can serve as the catalysts for addition of amines to nitriles to monosubstituted N-arylamidines. The activity depended on the central metals and amide groups, and the active sequence follows the trend IV ≈ III < I < II.     

Direct selective and controlled protection of multiple hydroxyl groups in polyols via iterative regeneration of stannylene acetals

A direct selective protection (O-benzylation) of two or more hydroxyl groups in polyols displaying diverse structural patterns was made possible by the establishment of conditions that enable an efficient turnover for the Bu₂Sn group, initially at the corresponding stannylene acetals (only ∼1.0 mol equiv of Bu₂SnO was employed). It was also demonstrated that one might exert control over the number of protected groups, by means of appropriate tuning of reaction conditions. The feasibility of a substoichiometric (tin source) catalytic protocol was demonstrated as well.