Aluminum Reagents Research Articles

ChemInform Abstract: Generation of Functionalized Aryl and Heteroaryl Aluminum Reagents by Halogen—Lithium Exchange.

AbstractVarious functionalized aryl aluminum reagents are obtained by performing halogen—Li exchange reactions with the corresponding aryl halides in the presence of iBu2AlCl.

A Large Scale Formal Synthesis of CoQ10: Highly Stereoselective Friedel-Crafts Allylation Reaction of Tetramethoxytoluene with (E)-4-Chloro-2-methyl-1-phenylsulfonyl-2-butene in the Presence of Montmorillonite K-10

Ubiquinone, as its name represents, exists ubiquitously in human body, particularly in the heart. It mediates the electron transfer process in mitochondria and also exerts strong antioxidant effect in its reduced form. In clinical trial, it showed beneficial effect on heart-related diseases such as myocardial infarction, angina, and other related symptoms to cause decreased mortality compared to the placebo group. These interesting biological effects have induced various synthetic efforts towards Coenzyme Q10 (CoQ10). Among them, two approaches seem practical for a large scale production in terms of the supply of the starting material, solanesol and their synthetic efficiency: for the construction of its complete carbon framework, Koo’s synthesis used the coupling of the sulfone 2 with solanesyl bromide (3) and Lipsultz group employed nickel catalyzed cross coupling reaction of 4 with vinyl aluminum reagent 5 as the key steps, respectively (Figure 1). Earlier in our synthetic study towards CoQ10, we investigated the reproducibility of the Koo’s synthetic procedure toward 2 obtained from the Friedel-Crafts reaction of (E)-4chloro-2-methyl-1-phenylsulfonyl-2-butene (7) with tetramethoxytoluene 6. Surprisingly, the reaction itself was pretty complicated with the formation of many side products in much lowered E:Z selectivity of ca. 3:1 to 7:1 than reported. Use of zinc chloride and bromide resulted in 3.3:1 and 7.4:1 E:Z ratio, respectively (Table 1, entries 1-2) with yields usually less than 20%. Best ratio of 7.6:1 was obtained by the use of boron trifluoride etherate, however with low conversion of ca. 20%. Aluminum chloride also showed marginal conversion of 21% with 3.4:1 E:Z selectivity. Details of the HPLC profiles of these reaction mixtures were provided in Figure 2. Other Lewis acid such as MgBr2, AlEt3, TiCl4, FeCl3 led to complete decomposition of starting materials and no sign of the formation of the desired product was observed by HPLC analysis. To improve the yield and stereoselectivity of the reaction, we turned our attention to the use of montmollironite K-10 (MK-10), in which the reaction partners might be confined in the layered space, thus rendering the stereoselectivity increased. First we tested commercial MK-10 for the reaction of 6 with 7. Happily, first attempt led to much cleaner reaction profile with significantly improved E:Z selectivity (Table 2, entry 1). However, the reaction did not complete in prolonged reaction time – the maximum conversion was accomplished in 18 h (74%). We speculated that the low conversion might be caused by residual water in clay (6.9% for commercial MK-10). In this respect, we tested a series of

ChemInform Abstract: Direct Pd‐Catalyzed Cross‐Coupling of Functionalized Organoaluminum Reagents.

AbstractA broad spectrum of aromatic or benzylic aluminum reagents, generated in situ from different types of substrates is demonstrated to give the expected products.

ChemInform Abstract: Iron‐Catalyzed Cross‐Coupling of Halohydrins with Aryl Aluminum Reagents: A Protecting‐Group‐Free Strategy Attaining Remarkable Rate Enhancement and Diastereoinduction.

AbstractThe cross‐coupling reaction of protected trans‐4‐chlorocyclohexanol derivatives with in situ formed aryl aluminum reagents proceeds with low diastereoselectivity whilst analogous reactions of unprotected trans‐4‐chlorocyclohexanol demonstrate a good trans‐selectivity.

Generation of functionalized aryl and heteroaryl aluminum reagents by halogen–lithium exchange

Various functionalized aryl and heteroaryl aluminum reagents were obtained by performing I-Li or Br-Li exchange reactions with the corresponding unsaturated organic halides in the presence of i-Bu2AlCl. By means of an appropriate catalyst, the resulting new aluminum species were directly acylated, allylated or arylated. 1,4-Michael additions to enones have also been achieved.

Catalytic Effect of Organoaluminium Chloride Reagents on the Dienophilic Reactivity of Indolizine and 2-Phosphaindolizine towards [2+4] Cycloaddition: A DFT Investigation

The catalytic effect of the aluminium chloride reagents R1AlCl2 (R1 = Cl, Me, Et) on the dienophilic reactivity of the >C=C< functionality of indolizine and >C=P- functionality of 2-phosphaindolizine in their Diels-Alder (DA) reaction with 1,3-butadiene has been investigated theoretically at the DFT (B3LYP/6-31+G**) level. The activation barriers of the DA reactions of the uncomplexed dienophiles with 1,3-butadiene are quite high. Co-ordination of the aluminium reagent to the carbonyl group of indolizine or 2-phosphaindolizine raises the activation barriers further. On the other hand, co-ordination of the aluminium catalyst to the σ2, λ3-P atom of 2-phosphaindolizine lowers the activation barrier making the DA reaction possible. Electronic structure calculations of indolizine, 2-phosphaindolizine and their complexes to the aluminium catalyst indicate, that this behavior can be explained by a combination of energetic and stereoelectronic influences of the catalyst on the lowest unoccupied molecular orbital (LUMO) of the dienophiles. Co-ordination of the aluminium catalyst to the dienophile lowers the orbital energy of the LUMO in any case making it energetically more feasible for the normal electron demand DA-reactions. However, O co-ordination polarizes the spatial distribution of the LUMO away from the dienophilic center while P co-ordination increases the orbital contribution of the >C=P fragment to the LUMO.

Production of coagulant reagents for electro-coagulation processes at low current densities

Abstract In this work, the electrochemical production with low current densities of iron and aluminium reagents for electro-coagulation processes has been studied. It has been found that pH is a very important parameter, being strongly related to the speciation of iron in terms of iron (II) or iron (III) species, and also to the efficiency of the electrochemical reagent-dosing process. Iron (II) species are only significant under acidic conditions because in neutral and alkaline conditions iron (II) is rapidly transformed into iron (III). Efficiencies in the dissolution of the metals are very high and, in some cases, over the value expected for a 100% – efficiency (super-faradaic efficiencies), due to the non-electrolytic dissolution of the electrodes, which is very important for iron under acidic conditions, and even more important for aluminium at alkaline pHs. This significant non-electrolytic contribution explains the different trends observed in the efficiency changes with current density.

Stereocontrol with Lithium Trimethylzincate toward Gibberellin Synthesis

AbstractSubstrate control in target‐oriented synthesis is generally important in establishing the required stereogenic center rather than reagent control. During the course of the total synthesis toward Gibberellin A3 (1), a model compound (21) as the A‐ring of 1 was accomplished in five overall steps with an overall yield of 15 %, starting from furfural through conjugate addition of lithium trimethylzincate to oxabicyclo[2.2.1]heptadienedicarboxylic ester (2) as the key step. Relative to more common lithium dimethylcuprate or aluminum reagents, this zincate complex showed a complete selectivity with higher reactivity than with other simple enone compounds. The incoming methyl group was 100 % selective from the ring oxygen side of 2, and the enolate intermediate can be protonated stereoselectivly without the bridge‐oxygen‐ring opening.

Iron-catalysed cross-coupling of halohydrins with aryl aluminium reagents: a protecting-group-free strategy attaining remarkable rate enhancement and diastereoinduction

Non-protected halohydrins are cross-coupled with aryl aluminium reagents to produce aryl alkanols in the presence of the iron-bisphosphine catalysts. Remarkable reaction rate enhancement and diastereoinduction are realized by the in situ generated aluminium alkoxides, offering a new method for the reactivity and selectivity control of the iron-catalysed cross-coupling reaction.

Structurally Powered Synergic 2,2,6,6-Tetramethylpiperidine Bimetallics: New Reflections through Lithium-Mediated Ortho Aluminations

Recent times have witnessed many notable advances in metalation chemistry with halide salt supported strategies and alkali-metal mediated metalation being particularly prominent. This article begins with a brief account of both of these avant garde metalation methods focusing on selected recent examples not covered previously in a review. New results in the area of Alkali-Metal Mediated Alumination (AMMAl) are also presented. Thus, the putative lithium aluminate base THF·Li(μ-TMP)(2)Al((i)Bu)(2) (4) is shown to act via TMP basicity to efficiently ortho deprotonate a variety of functionalized aromatic molecules at room temperature, tolerating carboxamide and halide functionalities. These metalated species are electrophilically quenched with elemental iodine. Crystal structure determinations of the metalated intermediates confirm unequivocally that direct alumination of the substrates has occurred. Since the homometallic lithium or aluminum reagents are unable to effect such deprotonations these reactions are synergic in nature and can be considered examples of AMMAl. Drawing together previously published work in the field of AMMAl, together with other pertinent experimental observations and new density functional theory (DFT) computational studies, we propose a potential rationale for the "unusual" reactivity patterns witnessed in this branch of heterometallic synthetic chemistry with respect to other Alkali Metal Mediated Metalations which appear to behave in a more conventional manner.

Studies on the active species in olefin polymerisation generated from phenoxo-amido titanium “ chiral-at-metal” compounds

Treatment of RHN-CH 2-(3,5-tBu 2C 6H 2-2-OH) (R = C 6H 5 1a, p-MeC 6H 4 1b, Cy 1c; Cy = cyclohexyl) with 1 equiv of TiCp∗Cl 3 (Cp∗ = η 5-C 5Me 5) in the presence of 2.5 equiv of NEt 3 in pentane or hexane at room temperature gives the monocyclopentadienyl phenoxo-amido monochloro complexes [TiCp∗{RN-CH 2-(3,5-tBu 2C 6H 2-2-O)}Cl] (R = C 6H 5 2, p-MeC 6H 4 4, Cy 5). In a more polar solvent the phenoxo-amino complex [TiCp∗{(C 6H 5)(H)N–CH 2-(3,5-tBu 2C 6H 2-2-O)}Cl 2] ( 3) is obtained from the reaction with 1a. The reaction of TiCp∗Cl 3 with tBu(H)N–CH 2-(3,5-tBu 2C 6H 2-2-OH) ( 1d) affords the complex [TiCp∗{tBu(H)N–CH 2-(3,5-tBu 2C 6H 2-2-O)}Cl 2] ( 6) in which no coordination of the amino group to the metal centre is observed as a consequence of the high steric requirements of the amino substituent in the phenol-amine. All the reported compounds were characterised by the usual analytical and spectroscopic methods and the molecular structures of 2 and 5 were determined by X-ray diffraction analysis from suitable single crystals. Studies of catalytic activity for ethylene or propylene polymerisation using boron or aluminium reagents as cocatalysts were performed under different conditions. In general the trends observed for the phenoxo-amido precatalysts with the aluminium reagent as cocatalyst in the α-olefin polymerisation reactions might suggest a catalyst decomposition process through ligand abstraction by sMAO. The activity found for ethylene or propylene polymerisation when B(C 6F 5) 3 or [CPh 3][B(C 6F 5) 4] are used as cocatalysts is related to the strength of the cation-anion interactions.

Enantioselective Synthesis of Alkyne-Substituted Quaternary Carbon Stereogenic Centers through NHC−Cu-Catalyzed Allylic Substitution Reactions with (i-Bu)2(Alkynyl)aluminum Reagents

A catalytic enantioselective method for the formation of alkyne-substituted all-carbon quaternary stereogenic centers is reported. Additions of alkynylaluminums to alkyl-, aryl-, carboxylic ester-, or silyl-substituted allylic phosphates are promoted by 1.0-5.0 mol % loadings of NHC-Cu complexes derived from air-stable and commercially available CuCl(2)·2H(2)O. The requisite Al-based reagents are prepared through treatment of the corresponding aryl-, heteroaryl-, alkyl-, or alkenyl-substituted terminal alkynes with diisobutylaluminum hydride in the presence of 5.0 mol % Et(3)N at ambient temperature. The desired 1,4-enynes are obtained in up to 98% yield and >99:1 enantiomeric ratio. Selected Au-catalyzed cyclizations involving the alkyne unit of the enantiomerically enriched products are presented as a demonstration of the method's utility in chemical synthesis.

ChemInform Abstract: Diastereoselective Synthesis of Homoallylic Alcohols with Adjacent Tertiary and Quaternary Centers by Using Functionalized Allylic Aluminum Reagents.

AbstractIt is demonstrated, that freshly generated allylic aluminum reagents react with aldehydes or ketones to give monoallyl alcohols.

ChemInform Abstract: Preparation of Organoaluminum Reagents from Propargylic Bromides and Aluminum Activated by PbCl2 and Their Regio‐ and Diastereoselective Addition to Carbonyl Derivatives.

AbstractTreatment of propargylic bromides with Al and PdCl2 allows mild and efficient access to propargylic and/or allenic aluminum reagents depending on the substitution pattern.

Diastereoselective Synthesis of Homoallylic Alcohols with Adjacent Tertiary and Quaternary Centers by Using Functionalized Allylic Aluminum Reagents

Al be there for you: Sensitive functional groups, including ester and cyano groups, can be present in allylic aluminum reagents prepared by aluminum insertion in the presence of InCl3. These aluminum organometallic compounds undergo addition reactions to various functionalized aldehydes or ketones with remarkable diastereoselectivities allowing the construction of two adjacent quaternary and tertiary centers (see scheme). Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

ChemInform Abstract: Chiral Lewis Acids in Catalytic Asymmetric Reactions

This review examines the recent advances in the use of chiral Lewis acids, usually generated in situ from a Lewis acid and a chiral auxiliary, in the Diels-Alder reaction, the ene reaction, the hydrocyanation of aldehydes, the ring-opening of epoxides and various miscellaneous reactions. Structural studies of the complex formed between carbonyl compounds and Lewis acids are also reported. The Sharpless epoxidation is not covered by this review. 1. Introduction 2. Asymmetric Diels-Alder Reactions 2.1. Chiral Titanium Reagents 2.2. Chiral Aluminum Reagents 2.3. Chiral Boron Reagents 2.4. Chiral Ruthenium Reagents 3. Asymmetric [2+2] Cycloaddition Reactions 4. Asymmetric Ene Reaction 5. Asymmetric Hydrocyanation of Aldehydes 6. Asymmetric Ring Opening of Epoxides 7. Miscellaneous Asymmetric Reactions 8. Structural Studies on the Complexes of Carbonyl Compounds and Lewis Acids

ChemInform Abstract: Asymmetric Hydride Reduction Using a Chiral Aluminum Reagent (I) Modified by a Crowned 2,2′-Dihydroxy-1,1′-binaphthyl.

ChemInform Abstract: Asymmetric Hydride Reduction Using a Chiral Aluminum Reagent (I) Modified by a Crowned 2,2′-Dihydroxy-1,1′-binaphthyl.

ChemInform Abstract: High Regioselectivity in the Alternative, Reductive Cleavages of Terminal Epoxides with Aluminum Reagents.

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Preparation of Organoaluminum Reagents from Propargylic Bromides and Aluminum Activated by PbCl2 and Their Regio‐ and Diastereoselective Addition to Carbonyl Derivatives

Various propargylic and allenic aluminum reagents have been easily prepared by a direct insertion of aluminum into propargylic bromides in the presence of PbCl(2) (1 mol%). These organoaluminum reagents react with carbonyl compounds to afford the corresponding allenic alcohols or homopropargylic alcohols in good to excellent yields with high regio- and diastereoselectivity.

Solution Reactions of a Bis(pyrrolylaldiminate)copper(II) Complex with Peralkyl Zinc, Aluminum, and Boron Reagents: Investigation of the Pathways Responsible for Copper Metal Deposition

The solution reactions of bis(N-isopropylpyrrolylaldiminate)copper(II) (CuL2) with AlMe3, BEt3, and ZnEt2 have been studied. In all cases, reduction occurs in two stages via a stable copper(I) pyrrolylaldiminate complex (Cu2L2), with each stage initiated by copper alkyl complex formation. Reduction from “LCuR” (R = Me or Et) occurs with release of R2 or L−R, consistent with bimolecular C−C or C−N bond-forming reductive elimination. At room temperature or below, copper deposition from “CuMe” occurs exclusively via reductive elimination of ethane, whereas decomposition of “CuEt” yields ethylene, ethane, and hydrogen, indicative of both β-hydride elimination and reductive elimination. The reaction byproducts [Cu2L2], [LAlMe2], [L2AlMe], [AlL3], [LBEt2], [LZnEt], [ZnL2], L−Me, and L−Et were synthesized independently and isolated as pure compounds. All compounds are thermally stable, with the exception of LZnEt, which undergoes ligand redistribution to form ZnL2 and ZnEt2 in solution and as a solid at elevated temperatures. With the exception of [LZnEt] and [Cu2L2], these complexes are also volatile; monoligated [LAlMe2] and [LBEt2] are particularly volatile, and therefore more desirable as byproducts in ALD or pulsed-CVD.