[61754-28-7]  · C14H22CoN5O4  · Bis(dimethylglyoximato)(methyl)(pyridine)cobalt(III)  · (MW 383.29)

(prototype of alkylcobaloximes and model compound for methylcobalamine1)

Alternate Names: methyl(pyridine)cobaloxime(III); MeCoIII(dmgH)2py.

Physical Data: mp 215-220 °C (dec); d 1.42 g cm-3; polarographic half-wave potentials (acetonitrile solution, vs Ag/AgNO3 electrode): -1.75, -2.44, -3.01 V; lmax = 438 nm (log ε = 3.17); 1H, 13C, 59Co NMR, and ESR data,2 FT-IR and Raman spectroscopy,3 polarographic properties (dropping mercury electrode),4 photochemical and radiolytic C-Co bond cleavage,5 thermal decomposition,6 and X-ray crystallography7 have been described.

Solubility: sol many organic solvents (acetone, methanol, methylene chloride); slightly sol THF, benzene, ethyl acetate; almost insol water.

Preparative Method: orange crystals readily available from cobalt(II) chloride, butane-2,3-dione dioxime (dimethylglyoxime, dmgH2), pyridine (py), and dimethyl sulfate or methyl iodide.8

Handling, Storage, and Precautions: requires no special handling procedures. It is less light-sensitive than its solutions, which tend to decompose with loss of methyl and formation of cobaloxime(II), but should be stored in amber colored vials under nitrogen. For some reactions the 4-t-butylpyridine derivative of methyl(pyridine)cobaloxime(III), i.e. methyl(4-t-butylpyridine)cobaloxime(III), is easier to handle especially when column chromatography on silica gel (ethyl acetate, orange band, Rf = 0.4) is required, or in applications which require higher concentrations of alkylcobaloxime(III) in solution or use of nonpolar solvents. Samples have been purified with reversed phase HPLC on a chromsil C18 column.9 Methyl(pyridine)cobaloxime is readily recrystallized from methanol/water mixtures under a nitrogen atmosphere.

General Preparation of Organocobalt(dmgH)2 Complexes.

Organo-CoIII(dmgH)2 complexes were originally developed by Schrauzer as vitamin B12 analogs9,10,11 (see also Cobalt Salen Complexes and Cobalt Salophen Complexes), and extensive mechanistic studies into their reactions have been carried out.10,12 The preparation of RCoIII(dmgH)2 complexes can be accomplished by reacting CoI(dmgH)2, CoII(dmgH)2, or CoIII(dmgH)2 reagents with electrophiles, radicals, and nucleophiles respectively.10 The most common method for the preparation of RCoIII(dmgH)2 reagents is via displacement reactions using supernucleophilic CoI(dmgH)2. CoI(dmgH)2 can be prepared in situ from the readily available CoII(dmgH)2 or ClCoIII(dmgH)2py by reduction with Sodium Borohydride8,13 or hydrogen gas,14 electrochemically,15 or by disproportionation.16 The reduced CoI(dm gH)2 reacts with a variety of substrates including alkyl halides, acyl halides, vinyl halides,17 alkynyl halides,18 activated aryl halides,19 alkyl tosylates, alkyl sulfates, alkyl phosphates,20 and oxiranes.21 Allylic halides and propargylic halides may undergo both SN2 and SN2 substitution, with steric factors largely determining the course of the reaction (eq 1).22 For base sensitive substrates, CoII(dmgH)2 can be used in conjunction with Zn metal and an alkylating agent (eq 2).23

CoI(dmgH)2 adds to activated alkenes and alkynes, e.g. styrene and acrylonitrile, in alkaline protic solvents to give b-substituted products arising from trans addition of the metal ion and a proton from the solvent (eq 3). Under neutral or acidic conditions, CoI(dmgH)2 exists as the protonated hydrido HCoIII(dmgH)2 species, and a-substituted products arising from a cis addition are isolated (eq 4).17 1,3-Dienes that do not possess terminal substituents react to give allylCoIII(dmgH)2 complexes (eq 5).24

ClCoIII(dmgH)2py reacts with alkyl metals such as Grignard reagents,25 alkyllithiums, alkylborons, and alkylaluminums, leading to the corresponding organo-CoIII(dmgH)2 complexes (eq 6).26 A one-pot procedure whereby CoI(dmgH)2 is formed in situ from a cobalt(II) salt, pyridine, and dimethylglyoxime under reducing conditions, followed by the addition of an alkylating agent, can be employed (eq 7).8


Methyl(pyridine)cobaloxime(III) is a methylating agent. Due to its covalent nature, the carbon-cobalt bond can be cleaved with nucleophiles, radicals, and electrophiles. For some transformations, photochemical, thermal, or oxidative activation of the carbon-cobalt bond may be required. Thiolates are methylated at room temperature (eq 8).

Thus in vitro methylation of coenzyme M with abiotic methyl(pyridine)cobaloxime(III) in basic alcoholic solutions and in the presence of cell extracts of Methanobacillus omelianskii yields methane, forming a model for methane biosynthesis.27 Likewise, nucleophiles such as SCN-, I-, CN-, and phosphines readily yield the corresponding methylated products. Electrophilic cleavage of the methyl carbon bond in methyl(pyridine)cobaloxime(III) occurs in the presence of Mercury(II) Acetate, Thallium(III) Acetate, and anhydrous acids, such as Trifluoroacetic Acid and Hydrochloric Acid.28 The former reaction mimics environmental formation of methylmercury via methylcobalamine in wastewater of heavily polluted industrial sites (eq 9).

Efficient and selective methyl transfer reactions from methyl(pyridine)cobaloxime(III) to a,b-unsaturated carbonyl compounds require assistance of palladium salts. Thus 1,4-benzoquinone is monomethylated in 70% yield in the presence of LiPdCl4 (eq 10). Terminal alkenes such as styrene, 1-octene, or acrylates form the corresponding chain elongated (E)-alkenes. Substitution of an alkyl group by hydrogen occurs at the sterically less hindered alkenic carbon atom (eq 11).29

Cleavage of alkyl-cobalt bonds with solutions of bromine in the dark has proven to be a useful tool for dealkylation of cobaloximes in both mechanistic and preparative studies.30 Due to the decreased oxidative power of iodine, alkylcobaloximes are converted to alkyl iodides only when the reaction mixtures are photolyzed.31 Cobalt(IV) species have been discovered by ESR spectroscopy to be the primary products of photolytic iodination of alkylcobaloximes, and these then fragment to yield alkyl iodides (eq 12).

Insertion Reactions of Organocobalt(dmgH)2) Complexes.

RCoIII(dmgH)2 complexes undergo insertion of molecular oxygen under thermal or photochemical conditions to give alkylperoxycobaloximes (ROOCoIII(dmgH)2).32 The reaction is accompanied by racemization with chiral organocobaloximes.33 ROOCoIII(dmgH)2 complexes can be reduced using NaBH4 or LiAlH4, leading to the corresponding alcohols (eq 13),15 and can act as sources of oxygen centered radicals.24 Similarly, sulfur dioxide inserts readily into both primary and secondary alkyl RCoIII(dmgH)2 complexes (eq 14). However, phenyl, vinyl, and styryl complexes have been shown to be inert to O2 and SO2.34 Homolysis of RCoIII(dmgH)2 complexes in the presence of carbon monoxide does not normally lead to acylcobalt complexes. If the reaction is carried out in an alcoholic solvent, however, then alkoxycarbonylCoIII(dmgH)2 (ROCOCoIII(dmgH)2) complexes are formed, where the alkoxy group is derived from the solvent (eq 15).35

Homolytic cleavage of RCoIII(dmgH)2 complexes in the presence of nitric oxide has been demonstrated. Thus mannosyl bromide yields the corresponding oxime via the mannosylcobaloxime (eq 16).36 However, either alkyl oximes or nitrates and alcohols can be formed, depending upon the structure of the alkylcobaloximes.37

Photolysis of methyl(pyridine)cobaloxime(III) in the presence of alkyl methacrylates leads to selective formation of a dimer.38 The primary step of this reaction is the formation of the methyl radical, which has been quenched with spin traps such as nitrosodurene or phenyl t-butyl nitrone.39 Methyl radicals add to the b-position of alkyl methacrylates. The persistent cobaloxime(II) radical which is present in solution traps the adduct radical and regenerates the unsaturation in the product via hydridocobaloxime formation. Hydridocobaloxime is the original catalyst for the dimerization of alkyl methacrylates, adding to the electron deficient acrylate and then formally inserting a second molecule of methacrylate via a radical-generation-alkene-trap-cobaloxime(II)-quench pathway. Subsequent hydridocobaloxime elimination regenerates the catalyst and expels the dimer (eq 17). General radical reactions are discussed in the following sections.

Radical Substitution Reactions.

Reactions between allylCoIII(dmgH)2 complexes and organic radicals generally proceed via a SH2 mechanism. Reactions between nitrogen, sulfur, and carbon centered radicals and allylCoIII(dmgH)2 complexes lead to a range of 3-substituted propenes (eq 18).40 Reaction of organic radicals with the terminal unsaturated carbon in but-3-enylCoIII(dmgH)2 complexes gives rise to functionalized cyclopropanes via an intramolecular homolytic displacement (eq 19).40 Alkyl-, allyl-, and benzylCoIII(dmgH)2 complexes have been photolyzed in the presence of sulfur and selenium radical traps to provide the corresponding functionalized products in good yield (eq 20).41

The allylic CoIII(dmgH)2 complex prepared from hydrocobaltation of myrcene undergoes trapping by TEMPO (2,2,6,6-Tetramethylpiperidin-1-oxyl) upon irradiation in toluene. The resulting hydroxylamine can then be reduced to both nerol and geraniol (eq 21).24 This conversion of a 1,3-diene to an allylic alcohol via the hydrocobaltation-oxidation sequence compares favorably with the related method of Suzuki utilizing Palladium(II) Chloride.

Radical Cyclization Reactions.

The ease of homolysis of the CoIII-carbon bond can be used to good effect in generating carbon centered radicals which can undergo inter- or intramolecular oxidative addition processes. Various 2-allyloxyethyl halides and tosylates react with CoI(dmgH)2 to give the corresponding tetrahydro-3-furanylmethylcobaloximes, which upon irradiation in benzene lead to products arising from b-elimination (eq 22).42 CoI(dmgH)2 generated electrochemically catalyzes the cyclization of bromoacetal alkenes to give ring-fused tetrahydrofurans (eq 23).43 In this case, as well as in other catalytic processes, the cyclizations are terminated reductively. An oxidative process has been developed to produce unsaturated b-oxy-g-butyrolactones via a CoI(dmgH)2 mediated cyclization of the corresponding vinyl ether bromoacetal (eq 24),44 and used in an approach to kainic acid (eq 25).45 Tandem radical cyclizations mediated by CoI(dmgH)2 are also possible, with the option that the process can be intercepted after the first cyclization if desired (eq 26).46

Radical cyclizations have also been initiated via the addition of CoI(dmgH)2 to oxiranes. In this case, irradiation of the intermediate b-hydroxycobaloximes with a sunlamp leads to efficient 6-exo-trig cyclizations followed by elimination of HCoIII(dmgH)2 (eq 27).47

Intermolecular Radical Addition Reactions.

Alkyl radicals produced from the homolysis of alkylCoIII(dmgH)2 complexes can be trapped in an intermolecular fashion by activated alkenes (eq 28).48 In these cases the unsaturated products are produced via the b-elimination of cobalt and hydrogen (dehydrocobaltation) from the intermediate cobaloxime. The sp2-sp2 coupling reaction between alkenes, involving a novel combination of hydrocobaltation-dehydrocobaltation reactions to and from alkenes, has been demonstrated.49 This overall transformation is a useful alternative to the Heck reaction which cannot be employed in the case of alkyl halides. Irradiation of glycosylcobaloximes in the presence of various activated alkenes has been shown to give rise to either addition or substitution products depending upon the electronic nature of the substitutents on the alkene substrate (eq 29).50 Nitroalkyl anions have also been employed in cross-coupling reactions giving rise to the corresponding nitro compounds in good yields (eq 30).51

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Bernd Giese

University of Basel, Switzerland

Jens Hartung

University of Würzburg, Germany

Gerald Pattenden & Andrew J. Clark

University of Nottingham, UK

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