Novel Mg-organic reagents in organic synthesis. Cp2TiCl2 catalyzed intermolecular cyclomagnesiation of cyclic and acyclic 1,2-dienes using Grignard reagents

High-yield (>80%) catalytic intermolecular cyclomagnesiation of cyclic and acyclic allenes with the aid of Grignard reagents has been realized in the presence of Cp₂TiCl₂. The synthesized unsaturated bi- and tricyclic organomagnesium compounds (OMC) have been successfully converted in situ into thiophenes, unsaturated ketones, cyclic and acyclic hydrocarbons with high regio- and stereoselectivity.     

A facile synthesis of spiro macrocarbocycles via the cycloalumination reaction of cyclic alkynes and alkadiynes

Zirconium-catalyzed cycloalumination of cycloalkadiynes assisted by Et₃Al, subsequent treatment of the in situ generated tricyclic dialuminum compounds with BrCH₂OMe and finally cyclopropanation of the obtained dispiro cyclopropyl dimethylene macrocarbocycles with Et₃Al-CH₂I₂ represents an efficient one-pot synthetic approach to prepare di- and tetraspiro cyclopropane-containing macrocarbocycles in very high yields.     

An efficient one-pot method for the synthesis of mono- and biscyclopentenones via zirconium-catalyzed cycloalumination of cyclic alkynes and diynes

Mono- and bisaluminacyclopentenes obtained via zirconium-catalyzed cycloalumination with Et₃Al and cyclic alkynes or diynes can be converted into the corresponding mono- and biscyclopentenones by treatment with CO₂, ClCOOEt, or CO(OEt)₂ in yields of 34−73%.     

The first one-pot synthesis of alkoxycyclopropanes via cyclometalation of styrene with ClnAlEt3−n and RCO2R′ mediated by Cp2ZrCl2

The one-pot cyclopropanation of styrene using Cl_nAlEt_3−n (Et₂AlCl, EtAlCl₂, AlCl₃) and carboxylic esters in the presence of Cp₂ZrCl₂ as catalyst gives rise to alkoxycyclopropanes.     

Targeted synthesis of 2,3-disubstituted 2-phospholenes using catalytic cycloalumination of acetylenes

A preparative one-pot method for the synthesis of 2,3-dialkyl-substituted phosphol-2-enes by catalytic cycloalumination of symmetric acetylenes with AlEt₃ catalyzed by Cp₂ZrCl₂ is developed. The reaction gives the corresponding aluminacyclopentenes, which then react in situ with phosphorus dihalides.     

Oxidations by the system “hydrogen peroxide-[Mn2L2O3][PF6]2 (L = 1,4,7-trimethyl-1,4,7-triazacyclononane)-oxalic acid”. Part 6. Oxidation of methane and other alkanes and olefins in water

Oxidation of alkanes with hydrogen peroxide in water solution at 10-50 °C is efficiently catalyzed by the cationic dinuclear manganese (IV) derivative [Mn₂L₂O₃]²⁺ (1, with L = 1,4,7-trimethyl-1,4,7-triazacyclononane, TMTACN) in the form of the hexafluorophosphate salt ([1][PF₆]₂) if oxalic acid is present as a co-catalyst. Methane gives methanol and formaldehyde (turnover numbers, TONs, were 7 and 2, respectively, after reduction of the reaction mixture with ascorbic acid) whereas cyclohexane was oxidized with TONs up to 160 affording cyclohexyl hydroperoxide, cyclohexanone and cyclohexanol (the ketone was the main product, although at room temperature almost pure alkyl hydroperoxide was formed). In contrast to the oxidation in acetonitrile, the reaction with linear n-alkanes in water exhibits an unusual distribution of oxygenates. For example, in the oxidation of n-heptane the normalized reactivity of the methylene group in position 4 of the chain is 3-7 times higher than that of the CH₂ group in position 2. Dec-1-ene is epoxidized by hydrogen peroxide in water (a biphasic system) catalyzed by [1][PF₆]₂ and oxalic acid in the presence of a small amount of acetonitrile with TONs up to 1000 (no epoxidation has been detected in the absence of MeCN).     

Catalytic cyclometalation reaction of unsaturated compounds in synthesis of magnesa- and aluminacarbocycles

The investigation results on design and application of the new catalytic cyclometalation reaction of olefins, dienes, acetylenes and allenes with Al, Mg and halogen alkyls mediated by Ti or Zr based metallocene catalysts to produce novel classes of cyclic organometallics namely aluminacyclopropanes, aluminacyclopropenes, aluminacyclopentanes, aluminacyclopentenes, aluminacyclopenta-2,4-dienes, magnesacyclopentanes, magnesacyclopentenes, magnesacyclopenta-2,4-dienes as well as metallamacrocycles are summarized and systematized. Selected literature data on thermal synthesis of cyclic organoaluminum and organomagnesium compounds for comparison the efficiencies of catalytic and classic synthetic methods are given. Mechanistic aspects of catalytic cyclometalation of unsaturated compounds and chemical transformations of Al and Mg metallacycles are discussed.     

Synthesis of methyl ketones from terminal olefins using PdCl2/CrO3 system mimicking the Wacker process

An efficient synthesis of methyl ketones from terminal olefins using PdCl₂/CrO₃ system mimicking the Wacker process is developed. The method shows good functional groups compatibility, no aldehyde by-products and is operationally simple. CrO₃ is the sole oxidant and replaces both Cu-salts and molecular oxygen, traditionally used in this process. The method holds potential for future applications in organic synthesis.     

Ruthenium complexes of the general formula [RuCl2(PHOX)2] and their catalytic activity in the Mukaiyama aldol reaction

New ruthenium phosphinooxazoline (PHOX) complexes were synthesized and applied in the Mukaiyama aldol reaction. Four ruthenium complexes of the general formula [RuCl₂(PHOX)₂] were synthesized from [RuCl₂(dmso)₄] and the corresponding PHOX ligands through thermal ligand exchange. Two of the complexes were characterized structurally. Achiral PHOX ligands gave the ruthenium complexes as single isomers, whereas chiral PHOX ligands gave a mixture of isomers and also some incomplete substitution. After activation by chloride abstraction, one of the new ruthenium complexes was applied as catalyst in the Mukaiyama aldol reaction to give silyl-protected β-hydroxyl alcohols in 74–92% isolated yields (room temperature, 18–24 h reaction time, 1 mol % catalyst loading).     

Theoretical study on the reaction mechanisms of ethylene with Cp2TiR, Cp2Ti(Cl)R, and Cp2Ti(Cl:AlH2Cl)R (R=H and CH3)

The potential energy surfaces for reactions of ethylene with Cp₂Ti⁺R, Cp₂Ti(Cl)R, and Cp₂Ti(Cl:AlH₂Cl)R (R=H and CH₃) were calculated by ab initio molecular orbital methods. These six reaction mechanisms were compared. Of the two possible reaction paths, attack of ethylene at Ti and the Cl and R ligands (path IN) and that from the opposite side of the Cl ligand (path OUT), the former is found to be more favorable, with a very low activation energy for reaction of ethylene with Cp₂Ti(Cl)H. For reaction of ethylene with Cp₂Ti(Cl)CH₃, the insertion transition states on both paths have almost the same energy barrier height above the reactants. For reaction of ethylene with Cp₂Ti(Cl:AlH₂Cl)R, the bond alternation between Ti–Cl and Cl–Al plays an important role in the mechanisms.     

Alkane oxidation by the H2O2-NaVO3-H2SO4 system in acetonitrile and water

A simple system is described, which oxidizes saturated hydrocarbons either in acetonitrile or (less efficiently) in water. The system consists of 50% aqueous hydrogen peroxide as an oxidant, sodium metavanadate, NaVO₃, as a catalyst and sulfuric (or oxalic) acid as a co-catalyst. The reactions were carried out at 20-50 °C. In the oxidation of cyclohexane in acetonitrile, the highest yield (37% based on cyclohexane) and turnover number (TON=1700) were attained after 3 h at 50 °C. The corresponding parameters were 16% and 1090 for n-heptane oxidation under the same conditions. The oxidation of higher alkanes, RH, in acetonitrile gives almost exclusively the corresponding alkyl hydroperoxides, ROOH. Light alkanes (n-butane, propane, ethane, and methane) have been also oxygenated by the system under consideration. The highest TON (200) was attained for ethane and the highest yield (19%) was obtained in the case of n-butane. The selectivity parameters measured for the oxidation of linear and branched alkanes are low, the reaction with cis- and trans-1,2-dimethylcyclohexanes is not stereoselective. These facts lead us to conclude that the oxidation occurs with the formation of hydroxyl radicals in the crucial step.     

Alkane oxygenation with H2O2 catalysed by FeCl3 and 2,2′-bipyridine

The H₂O₂-FeCl₃-bipy system in acetonitrile efficiently oxidises alkanes predominantly to alkyl hydroperoxides. Turnover numbers attain 400 after 1 h at 60 °C. It has been assumed that bipy facilitates proton abstraction from a H₂O₂ molecule coordinated to the iron ion (these reactions are stages in the catalytic cycle generating hydroxyl radicals from the hydrogen peroxide). Hydroxyl radicals then attack alkane molecules finally yielding the alkyl hydroperoxide.     

Direct formation of cyclobutenylphosphonates from 1-alkynylphosphonates and Cp2ZrCl2/2EtMgCl/2CuCl

Zirconacycles 2 prepared from 1-alkynylphosphonates 1, zirconocene dichloride, and 2 equiv of EtMgCl are smoothly converted into cyclobutenylphosphonates 3 when treated with two equiv of CuCl in 65-81% isolated yield. The reaction is specific and general only for zirconacyclopentenyl phosphonates.     

High yield thiolation of iodobenzene catalyzed by the phosphinite nickel PCP pincer complex: [NiCl{C6H3-2,6-(OPPh2)2}]

[NiCl{C₆H₃-2,6-(OPPh₂)₂}] efficiently catalyzes the thiolation of iodobenzene with a broad scope of disulfides in the presence of zinc, the coupled products are obtained in excellent and in many cases nearly quantitative yields.     

Cationic ruthenium complex of the formula [RuCl(2,6-diacetylpyridine)(PPh3)2]BArF and its catalytic activity in the formation of enol esters

A new ruthenium 2,6-diacetylpyridine complex was synthesized and applied in the atom-economic synthesis of enol esters through Markovnikov-directed addition of carboxylic acids to terminal alkynes. The ruthenium complex [RuCl(dap)(PPh₃)₂]⁺BArF^? was synthesized from [RuCl₂(PPh₃)₂] and the corresponding ligand 2,6-diacetylpyridine (dap). The complex was characterized structurally. The new ruthenium complex was utilized under ambient conditions as a catalyst in the Markovnikov addition of carboxylic acids to terminal alkynes to afford the corresponding enol esters in 93% to 52% isolated yields (85?°C, 16?h reaction time, 1?mol% catalyst loading).     

A unique rate-accelerating effect of certain amino acids in the H2O2 oxidation of alkanes catalyzed by a dinuclear manganese complex containing 1,4,7-trimethyl-1,4,7-triazacyclononane

Certain amino acids used in small amounts (10 catalyst equiv) strongly accelerate the H₂O₂ oxidation of cyclohexane catalyzed by a dinuclear manganese(IV) complex with 1,4,7-trimethyl-1,4,7-triazacyclononane. The efficiency of the co-catalyst dramatically depends on the nature and structure of the acid. Pyrazine-2,3-dicarboxylic acid (2,3-PDCA) has been found to be the most efficient co-catalyst whereas picolinic acid is almost inactive in this oxidation. The highest rate has been attained when 2,3-PDCA was used in combination with trifluoroacetic acid.     

Et2SiH2 assisted the selective dimerization of terminal alkynes catalyzed by Cp2UMe2

A practical approach has been developed for the catalytic synthesis of short oligomers, dimers and/or trimers of terminal alkynes. The method allows control of the extent and, in some cases, the regiospecificity in the catalyzed oligomerization of terminal alkynes promoted by bis(pentamethylcyclopentadienyl)uranium dimethyl complex (Cp^*₂U(CH₃)₂, Cp^*=C₅Me₅). The metallocene precursor is known to promote the simultaneous production of a large number of differently sized oligomers in the presence of terminal alkynes. However, the addition of a specific secondary silane ensures the selective synthesis of short oligomers.     

Amidocarbonylation of cyclohexene and 1-pentene with Co2(CO)8 modified with triarylstibines in very mild conditions

Interesting results, presenting the use of different stibine ligands in amidocarbonylation of cyclohexene and 1-pentene catalyzed by Co₂(CO)₈, not only enhance the activity of catalyst but also increases the selectivity in comparison to classical phosphinic ligands, have been reported. The stibine and phosphine ligands used were triphenylstibine (TPS), o- and p-tritolylstibine, (o-TTS, p-TTS) 2,4,6-trimesitylstibine (TMS), p-trifluorophenylstibine (p-TFPS), triphenylphosphine (TPP), o- and p-tritolylphosphine (o-TTP, p-TTP), respectively. All the reactions were carried out in a very mild syngas pressure (25 bar).     

Novel organomagnesium reagents in synthesis. Catalytic cyclomagnesiation of allenes in the synthesis of N-, O-, and Si-substituted 1Z,5Z-dienes

An efficient method for the synthesis of valuable N-, O-, and Si-containing 1Z,5Z-diene compounds was developed. The method comprises Cp₂TiCl₂-catalyzed homo- and cross-cyclomagnesiation of 1,2-dienes by Grignard reagents (RMgR′) to give 2,5-dialkylidenemagnesacyclopentanes in up to 96% yield. This approach was successfully used in the synthesis of 5Z,9Z-dienoic acids, precursors of acetogenins and insect pheromones.     

Efficient catalytic aza-Michael additions of carbamates to enones: revisited dual activation of hard nucleophiles and soft electrophiles by InCl3/TMSCl catalyst system

The aza-Michael reaction of a variety of chalcones with weaker nucleophilic carbamates catalyzed by InCl₃ in the presence of TMSCl via the entry of dual activation of both hard nucleophiles (carbamates) and soft electrophiles (enones) to provide the corresponding adducts in good yields. The first example of enantioselective aza-Michael reaction of chalcones with carbamates was also investigated in the presence of the present catalyst system.