Magnesium Reagents Research Articles

Difunctionalisation of Arenes and Heteroarenes by Directed Metallation and Sulfoxide–Magnesium Exchange

The aryl sulfoxide moiety allows an expedient two-step difunctionalisation of readily available diaryl sulfoxides. Highly functionalised 1,2,4-trisubstituted arenes and difunctionalised heteroarenes (furans, thiophenes, benzofurans and pyridines) were prepared in a two-step sequence, triggered by an aryl sulfoxide group. In the first step, the sulfoxide moiety acts as a metallation-directing group, allowing smooth ortho-magnesiation with TMPMgCl⋅LiCl (TMP=tetramethylpiperidine). After a quenching reaction with an electrophile, the resulting sulfoxide is converted into a second magnesium reagent with iPrMgCl⋅LiCl (sulfoxide-magnesium exchange), which can be trapped with various electrophiles. Highly chemoselective TMPMgCl⋅LiCl and iPrMgCl⋅LiCl are compatible with a broad range of functional groups (e.g., F, Cl, CF(3) , CN, CO(2) tBu, alkynyl, ethers, thioethers). Large-scale reactions (25-40 mmol) and the preparation of fully functionalised furans and thiophenes are also reported.

Novel Stable Silyl, Germyl, and Stannyl Germanium(II) Compounds Containing an Amidinato Ligand

Reactions of the N,N′-chelated chlorogermanium(II) compound [Me3SiNC(Ph)NSiMe3]GeCl with the magnesium reagents Mg[E(SiMe3)3]2 (E = Si, Ge, Sn) gave the new metallyl germylenes [Me3SiNC(Ph)NSiMe3]GeE(SiMe3)3, representing the first isolated silyl- and stannylgermylenes. These compounds have been fully characterized by multinuclear NMR spectroscopy and their structures determined by X-ray diffraction analysis.

Preparation of Heterocyclic Amines by an Oxidative Amination of Zinc Organometallics Mediated by CuI: A New Oxidative Cycloamination for the Preparation of Annulated Indole Derivatives

Functionalized heterocyclic zinc reagents are easily aminated by an oxidative amination reaction of zinc amidocuprates prepared from various lithium amides. For the oxidation step, PhI(OAc)(2) proved to be the best reagent. The required heterocyclic zinc organometallics can be prepared either by direct metalation, by magnesium insertion in the presence of ZnCl(2), or by transmetalation of a suitable magnesium reagent. Furthermore, we report a new ring-closing reaction involving an intramolecular oxidative amination reaction. This reaction allows the preparation of tetracyclic heterocycles containing furan, thiophene, or indole rings.

Trialkyl imido niobium and tantalum compounds: synthesis, structural study and migratory insertion reactions

Trialkyl imido niobium and tantalum complexes [MR(3)(NtBu)] (M = Nb, R = Me 2, CH(2)CMe(3)3, CH(2)CMe(2)Ph 4, CH(2)SiMe(3)5; M = Ta, R = Me 6, CH(2)CMe(2)Ph 7, CH(2)SiMe(3)8) have been prepared by treatment of solutions containing [MCl(3)(NtBu)py(2)] (M = Nb 1a, Ta 1b) with three equivalents of magnesium reagent. By an unexpected hydrolysis reaction of the tris-trimethylsilylmethyl imido tantalum compound 8a, a μ-oxo derivative [(Me(3)SiCH(2)O)(Me(3)SiCH(2))(3)Ta(μ-O)Ta(CH(2)SiMe(3))(2)(NtBu)] (8a) was formed and its structure was studied by X-ray diffraction methods. Reactions of trialkyl imido compounds with two equivalents of isocyanide 2,6-Me(2)C(6)H(3)NC result in the migration of two alkyl groups, leading to the formation of a series of alkyl imido bisiminoacyl derivatives [MR(NtBu){C(R)NAr}(2)] (Ar = 2,6-Me(2)C(6)H(3); M = Nb, R = Me 9, CH(2)CMe(3)10, CH(2)CMe(2)Ph 11, CH(2)SiMe(3)12, CH(2)Ph 13; M = Ta, R = CH(2)CMe(3)14, CH(2)CMe(2)Ph 15, CH(2)SiMe(3)16). All compounds were studied by IR and NMR ((1)H, (13)C and (15)N) spectroscopy.

Synthesis and characterization of poly(multidimethylsiloxane-1,4-ethynylenephenyleneethynylene)s

A series of poly(multidimethylsiloxane-1,4-ethynylenephenyleneethynylene)s were synthesized by condensation reactions of 1,4-diethynylbenzene magnesium reagents with various α,ω-dichlorodimethylsiloxanes. The polymers obtained were solids or viscous liquids and are soluble in common organic solvents at room temperature. The structures and properties of the polymers were characterized by Fourier transform infrared, 1H nuclear magnetic resonance (NMR), 13C NMR, differential scanning calorimeter (DSC), dynamic mechanical analysis (DMA) and thermogravimetric analysis (TGA) techniques. DSC analyses showed that these polymers can be thermally cured to form highly crosslinked structures. DMA studies revealed that the glass transition temperatures of the cured polymers decreased with increasing siloxane chain length. TGA measurements showed that the cured polymers were thermally stable up to almost 450 °C in both N2 and air. With increasing length of the siloxane units, the thermal stability of the cured polymers decreased. Silicon oxycarbide ceramics with high thermal stability were produced when the cured polymers were pyrolyzed at 1200 °C under argon. A series of poly(multidimethylsiloxane-1,4-ethynylenephenyleneethynylene)s were synthesized by condensation reactions of 1,4-diethynylbenzene magnesium reagents with various α,ω-dichlorodimethylsiloxanes. These polymers can be thermally cured to produce highly crosslinked structures. The glass transition temperatures of the cured polymers decrease with an increase in the siloxane chain length. The cured polymers are thermally stable up to almost 450 °C in both N2 and air. The silicon oxycarbide ceramics were obtained when the cured polymers were pyrolyzed at 1200 °C under argon.

ChemInform Abstract: Bromine-Magnesium-Exchange as a General Tool for the Preparation of Polyfunctional Aryl and Heteroaryl Magnesium-Reagents.

Abstract The scope of the BrMg-exchange reaction for the preparation of polyfunctional aryl and heteroaryl magnesium reagents has been studied. Various functional groups (ester, cyano, bromide) were tolerated in the exchange reaction allowing the preparation of polyfunctional Mg-reagents. Several dibromo- or tribromoheterocycles undergo a chemoselective mono-BrMg exchange leading to highly functionalized heterocycles.

Preparation of Functionalized Cyclic Enol Phosphates by Halogen−Magnesium Exchange and Directed Deprotonation Reactions

Cyclic enol phosphates were magnesiated by a halogen/magnesium exchange reaction or deprotonation using TMP-derived magnesium amide bases. The resulting magnesium reagents react readily with a wide range of electrophiles like allyl bromides and acid chlorides or can be used in Pd-catalyzed cross-coupling reactions. Several optically pure enol phosphates were prepared starting from readily available d-(+)-camphor derivatives.

Investigation on poly[(methylsilylene ethynylene phenylene ethynylene)- co-(tetramethyldisiloxane ethynylene phenylene ethynylene)

Poly[(methylsilylene ethynylene phenylene ethynylene)- co-(tetramethyldisiloxane ethynylene phenylene ethynylene)] was synthesized by polycondensation reaction of m-diethynylbenzene magnesium reagent with 1,3-dichlorotetramethyldisiloxane and dichloromethylsilane. The copolymer was characterized by FT-IR, 1H NMR, differential scanning calorimetry and thermogravimetric analysis. The results show that the copolymer exhibits good processability and cures at low temperatures. The cured copolymer shows high thermal stability.

Tetracycline antibiotics in hospital and municipal wastewaters: a pilot study in Portugal

This study investigated the occurrence of tetracyclines (TCs), namely minocycline (MIN), TC, and its epimer epitetracycline (ETC), and doxycycline (DC), in four hospital wastewater effluents and its fate in municipal wastewater treatment plants (WWTPs), in Coimbra, Portugal. Analytical determination was carried out by solid-phase extraction followed by liquid chromatography with fluorescence detection. A gradient system with a mobile phase containing oxalic acid 0.02 M and acetonitrile was used. After postcolumn derivatization with magnesium reagent, TCs were detected at lambda(exc) 386 nm and lambda(em) 500 nm. The proposed method allowed good sensitivity, accuracy, and precision. LOQs were 0.5 microg l(-1) for ETC and TC and 15 and 5 microg l(-1) for MIN and DC, respectively. The recovery values ranged between 66.4% and 117.1%, and intraday and interday repeatability was lower than 6.8%. The method was successfully used to determine the presence of the above-mentioned TCs in 24 wastewater composite samples obtained from hospital effluents and from influent and effluent of the WWTP located in Coimbra, Portugal. MIN and TC were found in 41.7% of the samples; ETC and DC were found in 25% and 8.3% of the samples, respectively. The levels found ranged from 6 to 531.7 microg l(-1) in hospital effluents, while its concentrations in WWTP ranged from 95.8 to 915.3 microg l(-1). A seasonal influence in the concentrations found has also been observed, the levels found in samples collected during spring being higher than those observed in samples collected during autumn; however, these are only preliminary results. The WWTP removal rate ranged between 89.5% and 100%.

Efficient Entry into 2-Substituted Tetrahydroquinoline Systems through Alkylative Ring Expansion: Stereoselective Formal Synthesis of (±)-Martinellic Acid

A new efficient synthesis of 2-substituted tetrahydroquinolines has been achieved by the domino reaction of N-indanyl(methoxy)amines, which consists of three types of reactions: elimination of an alcohol, the rearrangement of an aryl group, and the addition of an organolithium or magnesium reagent. The synthetic utility of this approach is demonstrated by the stereoselective formal synthesis of (+/-)- martinellic acid.

Iron-Catalyzed Cross-Coupling of Alkyl Sulfonates with Arylzinc Reagents

Iron-catalyzed cross-coupling reactions of primary and secondary alkyl sulfonates with arylzinc reagents proceed smoothly in the presence of excess TMEDA and a concomitant magnesium salt. The arylzinc reagents are prepared from the corresponding aryllithium or magnesium reagents with ZnI(2). The in situ formation of alkyl iodides and consecutive rapid cross-coupling avoids discrete preparation of the unstable secondary alkyl halides and also achieves high product selectivity.

Preparation of Polyfunctional Arylmagnesium, Arylzinc, and Benzylic Zinc Reagents by Using Magnesium in the Presence of LiCl

The presence of LiCl considerably facilitates the insertion of magnesium into various aromatic and heterocyclic bromides. Several functional groups, such as -OBoc, -OTs, -Cl, -F, -CF(3), -OMe, -NMe(2), and -N(2)NR(2), are well tolerated. The presence of a cyano group leads in some cases to competitive reduction of the organic halide to the corresponding ArH compound. The presence of sensitive groups such as methyl or ethyl ester is tolerated upon in situ trapping of the intermediate magnesium reagent with ZnCl(2). This method can also be applied to the preparation of functionalized benzylic zinc reagents from benzylic chlorides. In the case of di- or tribromoaryl derivatives, directing groups such as -OPiv, -OTs, -N(2)NR(2), or -OAc orient the zinc insertion (Zn/LiCl) to the ortho-position, while the reaction with Mg/LiCl or Mg/LiCl/ZnCl(2) leads to regioselective insertion into the para-carbon-bromine bond. Large-scale experiments (20-100 mmol) for all of the metalation procedures are described.

A Ligand Free and Room Temperature Protocol for Pd-Catalyzed Kumada−Corriu Couplings of Unactivated Alkenyl Phosphates

Kumada-Corriu cross-couplings of nonactivated cyclic and acyclic vinyl phosphates with aryl magnesium reagents afforded a series of 1,1-disubtituted alkenes in good yields for most cases when the reactions were performed at room temperature with the simple palladium salt, PdCl(2), without the presence of phosphine ligands.

C−F Bond-Cleavage Reactions of Fluoroalkanes with Magnesium Reagents and without Metal Catalysts

An unexpected C-F bond-cleavage reaction of unactivated fluoroalkanes with the well-known Grignard reagents without using metal catalysts has been discovered. For example, a reaction between 1-fluorooctane and phenyl magnesium chloride gave n-octylbenzene in moderate yield. This coupling reaction via the activation of an unactivated alkyl carbon-fluorine bond proceeds with phenylmagnesium chloride, whereas methylmagnesium chloride did not give the C-C cross-coupling product but rather a halogen exchange product.

Meta- and Para-Difunctionalization of Arenes via an Ortho-Magnesiation and a Subsequent Sulfoxide-Magnesium Exchange

; Highly functionalized 1,2,4-trisubstituted arenes can be prepared on large scale by a two-step sequence, triggered by an aryl sulfoxide group. In the first step, the sulfoxide moiety acts as a metalation directing group, allowing a smooth magnesiation with tmp-MgCl-LiCl. After a quenching reaction with an electrophile, the resulting sulfoxide is converted with i-PrMgCl·LiCl into a second magnesium reagent (sulfoxide-magnesium exchange), which can be trapped with various electrophiles. The highly chemoselective tmpMgCl·LiCl and i-PrMgCl·LiCl are compatible with a broad range of functional groups (FG = F, Cl, CF 3 , CN, CO 2 t-Bu, alkynyl).

ChemInform Abstract: Efficient Iridium‐Catalyzed C—H Functionalization/Silylation of Heteroarenes.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Diastereoselective Synthesis of N-Secondary Alkyl 2-Alkoxymethylpyrrolidines via Sequential Addition Reactions of Organolithium and -Magnesium Reagents to N-Thioformyl 2-Alkoxymethylpyrrolidines

Highly efficient sequential addition reactions of organolithium and -magnesium reagents to N-thioformyl 2-methoxymethylpyrrolidine have been described. Various combinations of these reagents gives successful results. A highly efficient and diastereoselective addition reaction is also described. Use of the opposite combinations of substituents on organolithium and -magnesium reagents leads to the selective formation of the opposite diastereomers. The reaction was extended to N-thioformyl 2-siloxymethypyrrolidine and 2-methoxymethylpiperidine, and these showed similar efficiency and selectivity.

A Mild Access to Aryl Magnesium Reagents

The authors present a mild route to a variety of aryl magnesium reagents that can be directly used in Negishi cross-coupling reactions or transmetalated for other C-C cross-couplings. Halogenated (Cl or Br) aromatics or heteroaromatics were treated with Mg(0) in the presence of LiCl at temperatures between -20 and 25 ˚C for 10 minutes to three hours. Less stable magnesium reagents like ester 5 could be transformed into their zinc derivatives 6 in situ and were further used in copper- or palladium-catalyzed reactions.

Efficient Iridium‐Catalyzed CH Functionalization/Silylation of Heteroarenes

As a consequence of their unique chemical, physical and biological properties, silyl-substituted arenes have attracted wide interest from the synthetic,[1] material science,[2] and pharmaceutical sectors.[3] Traditionally, silyl substituents have been introduced via addition of aryl lithium or magnesium reagents to silicon electrophiles, although this often necessitates the use of protecting groups.[4] Consequently, transition metal catalyzed cross couplings of aryl halides with disilanes or hydrosilanes have grown in popularity, especially if base-or nucleophile-sensitive functionality are present.[5] More recently, direct C-H functionalization[6] has emerged as a conceptually and economically attractive alternative for the direct silylation of arenes. It is evident, however, that challenges remain and the general utility of this strategy is restricted in many instances by, inter alia, (1) poor regioselectivity, (2) stringent structural requirements, (3) noncommercial/expensive reagents, (4) harsh reaction conditions (typically 120°–200°C), and/or (5) impractical ratios of arene to silicon reagent (10:1 to 60:1).[7–9] Herein, we report an efficient, regioselective protocol for the bipyridine-ligated, iridium-catalyzed[9] C-H functionalization/silyation of a wide variety of heteroarenes under comparatively mild conditions. Importantly, the reaction does not require protection of N-H groups and uses only a small excess (3 equiv) of inexpensive triethylsilane (eq 1).

Convenient Preparation of Polyfunctional Aryl Magnesium Reagents by a Direct Magnesium Insertion in the Presence of LiCl

Convenient Preparation of Polyfunctional Aryl Magnesium Reagents by a Direct Magnesium Insertion in the Presence of LiCl