Organoaluminum Reagents Research Articles

Development of Efficient Synthetic Reactions Using Enamines and Enamides Carrying Oxygen Atom Substituent on Nitrogen Atom.

We have developed efficient synthetic reactions using enamines and enamides carrying oxygen atom substituent on nitrogen, such as N-alkoxyenamines, N,α-dialkoxyenamines, N-alkoxyanamides, and N-(benzoyloxy)enamides. The umpolung reaction by polarity inversion at the β-position of N-alkoxyenamines afforded α-alkyl-, α-aryl-, α-alkenyl-, and α-heteroarylketones by using aluminum reagent as nucleophiles. Furthermore, one-pot umpolung α-phenylation of ketones has been also developed. We applied this method to umpolung reaction of N,α-dialkoxyenamine, generated from N-alkoxyamide to afford α-arylamides. The vicinal functionalization of N-alkoxyenamines has been achieved with the formation of two new carbon-carbon bonds by using an organo-aluminum reagent and subsequent allyl magnesium bromide or tributyltin cyanide. A sequential retro-ene arylation has been developed for the conversion of N-alkoxyenamides to the corresponding tert-alkylamines. The [3,3]-sigmatropic rearrangement of N-(benzoyloxy)enamides followed by arylation afforded cyclic β-aryl-β-amino alcohols bearing a tetrasubstituted carbon center. The resulting products were converted into the corresponding sterically congested cyclic β-amino alcohols, as well as the dissociative anesthetic agent Tiletamine.

Copper-assisted palladium catalyzed the cross-coupling reaction of Alknylalane reagents with 2-Thiobenzo[d]thiazoles via C–S bond cleavage

A highly efficient and simple route for the synthesis of 2-alknyl benzo[d]thiazoles has been developed by palladium and copper catalyzed the cross-coupling reaction of 2-thiobenzo[d]thiazoles with (hetero)aromatic and aliphatic alkynylaluminum reagents. Various 2-alkynyl benzo[d]thiazole derivatives can be obtained in 19–97 % isolated yields using 1 mol% PdCl2(dppf)/5 mol% xanthpos as the catalyst and CuI (3 equiv.) as desulfurization agent. The cross-coupling reaction can be carried out smoothly with electron-donating or -withdrawing groups on the aromatic ring of the organo aluminum reagents or the 2-thiobenzo[d]thiazoles. Furthermore, the broad substrate scope and the maintenance of high efficiency on a gram scale make this protocol a potentially practical method to synthesize 2-alkynylbenzo[d]thiazole derivatives. On the basis of the experimental results, a possible catalytic cycle has been proposed.2009 Elsevier Ltd. All rights reserved.

Synthesis of ortho-Methylated Benzamides via Palladium-Catalyzed Denitrogenative Cross-Coupling Reaction of [1,2,3]-Benzotriazin-4(3H)-ones with DABAL-Me3.

We herein developed a palladium-catalyzed reaction of [1,2,3]-benzotriazin-4(3H)-ones with DABAL-Me3 [bis(trimethylaluminum)-1,4-diazabicyclo[2.2.2]octane adduct], a cheap, stable, and solid organoaluminum reagent. In the presence of Pd(OAc)2/XantPhos as a commercially available catalyst, [1,2,3]-benzotriazin-4(3H)-ones underwent denitrogenative coupling with DABAL-Me3 to afford a wide array of N-aryl amides derived from ortho-methylated carboxylic acids. Under the same catalytic conditions, ortho-ethylation of [1,2,3]-benzotriazin-4(3H)-ones could also be achieved by using triethylaluminum.

Intermediates and mechanism in iron-catalyzed C-H methylation with trimethylaluminum.

A mechanistic study is performed on the reaction method for iron-catalyzed C-H methylation with AlMe3 reagent, previously proposed to involve cyclometalated iron(III) intermediates and an iron(III)/(I) reaction cycle. Detailed spectroscopic studies (57Fe Mössbauer, EPR) during catalysis and in stoichiometric reactions identify iron(II) complexes, including cyclometalated iron(II) intermediates, as the major iron species formed in situ under catalytic reaction conditions. Reaction studies identify a cyclometalated iron(II)-methyl species as the key intermediate leading to C-H methylated product upon reaction with oxidant, consistent with a previously proposed iron(II)/iron(III)/iron(I) reaction manifold for C-H arylation.

A General and Selective Synthesis of Methylmonochlorosilanes from Di-, Tri-, and Tetrachlorosilanes.

Direct catalytic transformation of chlorosilanes into organosilicon compounds remains challenging due to difficulty in cleaving the strong Si-Cl bond(s). We herein report the palladium-catalyzed cross-coupling reaction of chlorosilanes with organoaluminum reagents. A combination of [Pd(C3H5)Cl]2 and DavePhos ligand catalyzed the selective methylation of various dichlorosilanes 1, trichlorosilanes 5, and tetrachlorosilane 6 to give the corresponding monochlorosilanes.

Influence of Some Factors on the Progress of a New Reaction in the Chemistry of Organoaluminum Compounds

We earlier discovered a new reaction in the chemistry of organoaluminum compounds (OACs), specifically, the formation of O-isobutyl acetals on low-temperature (–70°C) treatment of seven-membered lactones with a double (or more) molar amount of diisobutylaluminum hydride (DIBAH) in methylene chloride. To assess the boundaries for the formation of isobutyl acetals depending on the ring size, we involved in the low-temperature hydride reduction six-, eight-, and thirteen-membered lactones. To determine how the scope of the new reaction depends on the nature of the organoaluminum reagent, we tested triisobutylaluminum (TIBA). To determine how the formation of isobutyl acetals on low-temperature (–70°C) reduction with excess DIBAH in CH2Cl2 depends on whether the starting ester is cyclic or acyclic and, if the former is the case, on the ring size in the ester, we used the acyclic methyl octadecanoate as the starting compound. It was found that the new reaction in the chemistry of AOC with DIBAH as the reducer is characteristic only of seven-membered lactones and atypical of acyclic methyl octadecanoate and ricinoleate (i.e. acids with the carbon chain length more than 6).

Cobalt-Catalyzed Decarboxylative Methylation and Ethylation of Aliphatic N-(Acyloxy)phthalimides with Organoaluminum Reagents

A cobalt-catalyzed decarboxylative methylation of aliphatic redox-active esters [N-(acyloxy)phthalimides; RAEs] with trimethylaluminum under mild conditions was developed, providing a method for transforming a carboxylate group into a methyl group without redox fluctuation. Primary and secondary RAEs were both amenable substrates, whereas a tertiary RAE delivered an elimination product. Triethylaluminum was also used to deliver a decarboxylative ethylation product.

Rotation-Triggered Transmetalation on a Heterobimetallic Cu/Al N-Phosphine-Oxide-Substituted Imidazolylidene Complex.

A novel strategy for the preparation of heterobimetallic N-heterocyclic carbene (NHC) complexes is demonstrated using N-phosphine-oxide-substituted imidazolylidenes (PoxIms). In these heterobimetallic Cu/Al complexes, the Cu and Al centers can be either completely separated or brought near each other via the rotation of the N-phosphinoyl group in the PoxIm ligands. Triggered by this rotation, transmetalation to exchange the Cu-OtBu and Al-C6F5 bonds occurs on in situ-generated Cu/Al PoxIm complexes, and the Cu-C6F5 and Al-OtBu bonds are formed in excellent yield. On the basis of the results of mechanistic studies, including the isolation/in situ observation of key complexes and theoretical calculations, a plausible reaction mechanism for an intramolecular transmetalation is proposed to proceed via an activation complex that includes the simultaneous coordination of the phosphinoyl oxygen atom to the Cu as well as the Al centers. Furthermore, the formation of carbon-carbon bonds between Al(C6F5)3 and allyl bromide mediated/catalyzed by Cu/Al PoxIm complexes is demonstrated. Upon the consecutive transfer of three C6F5 groups from a single molecule of Al(C6F5)3, allyl pentafluorobenzene derivatives were obtained. The present results demonstrate the role of phosphine oxide in the activation of organoaluminum reagents for the transmetalation between Cu(I) complexes bearing NHCs as well as the benefit of constructing an intramolecular system based on a heterobimetallic complex to achieve efficient transmetalation by programming the encounter of two organometallic fragments.

Rare-Earth Catalyzed C-H Bond Alumination of Terminal Alkynes.

Organoaluminum reagents' application in catalytic C-H bond functionalization is limited by competitive side reactions, such as carboalumination and hydroalumination. Herein, rare-earth tetramethylaluminate complexes are shown to catalyze the exclusive C-H bond metalation of terminal alkynes with the commodity reagents trimethyl-, triethyl-, and triisobutylaluminum. Kinetic experiments probing alkyl-group exchange between rare-earth aluminates and trialkylaluminum, C-H bond metalation of alkynes, and catalytic conversions reveal distinct pathways of catalytic aluminations with triethylaluminum versus trimethylaluminum. Most significantly, kinetic data point to reversible formation of a unique [Ln](AlR4 )2 ⋅AlR3 adduct, followed by turnover-limiting alkyne metalation. That is, C-H bond activation occurs from a more associated organometallic species, rather than the expected coordinatively unsaturated species. These mechanistic conclusions allude to a new general strategy for catalytic C-H bond alumination that make use of highly electrophilic metal catalysts.

Palladium-Catalyzed Synthesis of 1,2-Diketones from Aryl Halides and Organoaluminum Reagents Using tert-Butyl Isocyanide as the CO Source.

In this work, an interesting and practical procedure for the synthesis of 1,2-diketones from aryl halides and organoaluminum reagents has been developed. Employing tert-butyl isocyanide as the CO source and palladium as the catalyst, the desired 1,2-diketones were isolated in good to excellent yields with good functional group tolerance. Concerning the reaction partners, besides aryl halides, both alkyl- and arylaluminum reagents were all suitable substrates here.

Nickel‐mediated cross‐coupling via C–O activation assisted by organoaluminum

AbstractWe report the alkylation and arylation cross‐coupling of aryl ethers based on C–O bond activation using a nickel catalyst and organoaluminum reagents. Ni(cod)2 in combination with 1,2‐bis(dicyclohexylphosphino)ethane ligand in toluene solution at 130°C are the best conditions. The naphthyl ether or methoxy pyridine derivatives are suitable substrates for alkylation and arylation reaction with a wider scope of aluminum reagents in good yields. Computational analysis on the pyridine substrate is provided to help delineate the mechanistic pathway and demonstrate the important aspects of the cooperative interaction bimetallic catalysis. First, the coordination of AlMe3 to the O atom of pyridine is essential for C–O activation. Second, the β‐H transfer from methoxy to pyridine could be discouraged through the use of bidentate phosphine as a ligand. Finally, excess AlMe3 reagent is critical for facilitating a reductive elimination process.

Nickel-catalyzed cross-coupling of organoaluminum reagents with alkynylhalides for the synthesis of symmetrical and unsymmetrical conjugated 1,3-diynes derivatives

We describe a convenient method for the synthesis of symmetrical and unsymmetrical conjugated 1,3-diynes from cross-coupling reactions of organoaluminum with alkynylhalides: The cross-coupling reaction of organoaluminum (0.75 mmol) with alkynylhalides (0.5 mmol) mediated by Ni(acac)2 (5 mol%)/DPPE(10 mol%) at room temperature in DME may produce symmetrical and unsymmetrical conjugated 1,3-diynes in moderate to good yields(up to 98%) derivatives. Their structures have been determined by HRMS and 1H(13C)NMR data. On the basis of the experimental results, a possible catalytic cycle has been proposed.

Iron-catalyzed Alkyl–Alkyl Negishi Coupling of Organoaluminum Reagents

The first iron-catalyzed cross-coupling reaction of alkyl halides with alkylaluminum reagents (alkyl–alkyl Negishi coupling) is developed using an iron/bisphosphine catalyst system. The reaction sh...

Nickel‐Catalyzed Selective Cross‐Coupling of Chlorosilanes with Organoaluminum Reagents

AbstractNickel‐catalyzed cross‐coupling reactions of chlorosilanes with organoaluminum reagents were developed. An electron‐rich Ni(0)/PCy3 complex was found to be an effective catalyst for the desired transformation. The reaction of dichlorosilanes 1 proceeded to give the corresponding monosubstituted products 2. Trichlorosilanes 4 underwent selective double substitution to furnish the corresponding monochlorosilanes 2. Overall, the selective synthesis of a series of alkylmonochlorosilanes 2 from di‐ and trichlorosilanes was achieved using the present catalytic systems.

Enantioselective Aluminum-Free Alkene Hydroarylations through C-H Activation by a Chiral Nickel/JoSPOphos Manifold.

Highly enantioselective nickel-catalyzed alkene endo-hydroarylations were accomplished with full selectivity by organometallic C-H activation. The asymmetric assembly of chiral six-membered scaffolds proved viable in the absence of pyrophoric organoaluminum reagents within an unprecedented nickel/JoSPOphos manifold.

Enantioselective Aluminum‐Free Alkene Hydroarylations through C−H Activation by a Chiral Nickel/JoSPOphos Manifold

AbstractHighly enantioselective nickel‐catalyzed alkene endo‐hydroarylations were accomplished with full selectivity by organometallic C−H activation. The asymmetric assembly of chiral six‐membered scaffolds proved viable in the absence of pyrophoric organoaluminum reagents within an unprecedented nickel/JoSPOphos manifold.

Action of Organoaluminum Reagents on Esters: Alkene Production and the Degradation of Synthetic Lubricants

Reactions of methylaluminum reagents with ester-based lubricating oils are mimicked through the reaction of trimethylaluminum (TMA) with tetraesters C(CH2OC(O)R)4 (R = C5H11 4Pent, Bn 4Bn). Using a 2:1 stoichiometry gave adduct 4Pent(TMA)4. NMR spectroscopy on 1:1–12:1 TMA/4Pent systems suggested 4Pent gave dimethylated adduct C5H11CMe2OAlMe2(TMA), 2Pent(TMA). Similar combination of TMA with 4Bn at raised temperatures transformed 4Bn into C(CH2OAlMe2)4(2Bn)4 5(2Bn)4 by sequential reaction of each ester group. Doubly reacted {BnC(O)OCH2}2C(CH2OAlMe2)2(2Bn)2 7Bn(2Bn)2 was isolated and characterized. A Mitsubishi molecule could also be isolated, its formation rationalized by the elimination of 2Bn and TMA from 5(2Bn)4. The action of MenAlCl3–n (n = 1, 1.5, 2) was studied initially on monoester BnC(O)OMe 1Bn. Combining excess Me2AlCl with 1Bn gave adduct 1Bn(Me2AlCl) and small amounts of dimethylated BnCMe2OAlMe2(Me2AlCl), 2Bn(Me2AlCl), and MeOAlCl2 10. 2Bn(Me2AlCl) was fully characterized and, in the presence of 10, acted as a source of 2Bn(MeAlCl2). From this species, a mixture of alkenes could be generated by formal elimination of Me3Al2(OH)Cl2 13, the decomposition of which was presumed to also explain MeH observation. Replacing Me2AlCl with aluminum sesquichloride or MeAlCl2 led to progressively more sluggish but similar reactions. Using MenAlCl3–n (n = 1, 1.5, 2) with tetraesters suggested similar reactivity to monoesters.

An Alumino-Mannich Reaction of Organoaluminum Reagents, Silylated Amines, and Aldehydes.

A multi-component coupling using organoaluminum reagents, silylated amines, and aldehydes results in the formation of tertiary amines. Both alkenyl- and alkylaluminum reagents undergo reaction with iminium ion substrates for which the corresponding Petasis borono-Mannich reactions are unsuccessful.

Synthesis of multi-substituted allenes from organoalane reagents and propargyl esters by using a nickel catalyst.

A highly efficient and simple route for the synthesis of multi-substituted allenes has been developed by a nickel catalyzed SN2' substitution reaction of propargyl esters with organic aluminium reagents under mild conditions, which gave the corresponding multi-substituted allenes in good to excellent yields (up to 92%) and high selectivities (up to 99%) at 60 °C for 6 h in THF. Aryls bearing electron-donating or electron-withdrawing groups in propargyl esters gave products in good yields. In addition, the multi-substituted allenes bearing a thienyl or a pyridyl group were obtained in 95-97% selectivities with isolated yields of 72-83%. Furthermore, the SN2' substitution reaction worked efficiently with propargyl carbonate compounds as well. On the basis of the experimental results, a possible catalytic cycle has been proposed.

Ni-Catalyzed Formal Carbonyl-Ene Reaction of Terminal Alkenes via Carbon Dioxide Insertion

Nickel catalyzes the multicomponent coupling reaction of terminal alkenes, carbon dioxide, and organoaluminum reagents, leading to the synthesis of homoallylic alcohols in moderate-to-good yields with excellent regio- and stereoselectivities.