Sodium Bis(dimethylglyoximato)(pyridine)cobaltate1

[75699-52-4]  · C13H19CoN5NaO4  · Sodium Bis(dimethylglyoximato)(pyridine)cobaltate  · (MW 391.29)

(supernucleophilic cobalt complex;1 reagent for preparation of alkylbis(dimethylglyoximato)(pyridine)cobalt(III) complexes (alkylcobaloximes)2 and for formation of metal-cobalt bonds;3 reducing agent; reagent for reductive formation of carbon-carbon bonds,4 initializing ring expansions from cyclic halomethyl derivatives5 and cleavage of N-terminal protecting groups of peptides6)

Alternate Name: sodium cobaloxime(I).

Physical Data: dark purple to brown solid; no melting point has been reported; UV/vis in methanol: lmax = 641, 550, 458 nm.

Solubility: sol oxygen-free alcohols (ethanol, methanol), pyridine; insol ethers (THF, diethyl ether).

Preparative Methods: the reagent is prepared in situ from Cobalt(II) Chloride, butane-2,3-dione dioxime (dimethylglyoxime, dmgH2), Pyridine, Sodium Hydroxide and Sodium Borohydride in methanol at temperatures between -78 °C and rt. Addition of triethanolamine and its hydrochloride buffers solutions for base-labile alkylating reagents. Pyridine can be replaced by other heterocyclic nonreducible bases such as substituted pyridines, phosphines, anilines, imidazoles, trialkylamines, thioethers, arsines, or stibines. Water is an especially useful leaving group in alkylcobaloximes(III) for axial ligand exchange as it can fine tune the reactivity or solubility of the cobalt complex.7

Another convenient preparation of cobaloximes(I) uses cobalt(II) chloride, dimethylglyoxime, and an excess of sodium hydroxide. The strong basic reaction conditions lead to disproportionation of cobaloxime(II) to cobaloxime(I) and cobaloxime(III), both as their aqua complexes. Alkylation of the nucleophilic cobaloxime(I) with nonbase-labile alkyl halides or sulfonates yields alkylbis(dimethylglyoximato)(aqua)cobalt(III).8 Alkylaqua complexes of cobalt(III) are more soluble in alcohols or water than their pyridine derivatives, and thus are well suited for introducing any ligand which is more prone to bind to coordinated cobalt(III) than water (the latter property is in general well correlated with the nucleophilicity of the axial ligand in question) (eq 1).

The reagent can also be synthesized by alkali borohydride or alkali amalgam reduction of previously isolated and recrystallized halogenocobaloximes(III).9 This process is of interest whenever high purity cobaloxime(I) solutions are needed. Some applications of cobaloxime(I) require nonbasic conditions. Thus reacting cyanoethylcobaloxime with potassium t-butoxide leads to acrylonitrile elimination and potassium cobaloxime(I)10 (eq 2).

Handling, Storage, and Precautions: extremely air- and acid-sensitive; the reagent should be used as prepared in oxygen-free solutions at temperatures between -78 °C and rt by adding oxygen-free alkyl halides or sulfonates. Solid reagents, i.e. alkylating reagents, should be dissolved in acetone for best results, with halogenated solvents, i.e. carbon tetrachloride or methylene chloride, being avoided as they lead to the immediate formation of chloromethylbis(dimethylglyoximato)(pyridine)cobalt(III).2e

Cobalt is the catalytic center of vitamin B12 and therefore an essential trace element. However, care should be taken while handling inorganic cobalt(II) salts because they are potential carcinogens on parenteral application (i.e. bypassing the digestive system). Use in a fume hood.


Alkylation of supernucleophilic sodium cobaloxime(I) has been reported for a variety of primary and secondary alkyl halides,2a,b sulfonates,2c epoxides,2d electron-deficient alkenes,2e or perfluoroalkyl iodides.2f Sodium cobaloxime(I) adds in a Michael fashion to acrylic acid derivatives or acrylonitrile (eq 3).

Hydridocobaloxime can be prepared from cobaloxime(II) or sodium cobaloxime(I) under a hydrogen atmosphere. Hydridocobaloxime adds to a,b-unsaturated carbonyl compounds or aryl substituted alkynes with the opposite regioselectivity of that of sodium cobaloxime. This process can be used for selective isotope labeling (eq 4),11 when the reaction is carried out in deuterated media under a deuterium atmosphere.

The stereochemistry of the alkylation reaction is largely governed by the substrate. Kinetic data indicates an SN2 mechanism operating for simple primary and secondary alkyl bromides.1 In other cases, reaction pathways are derived from product distributions via SN2 reactions, e.g. for 4-substituted t-butylcyclohexanes (eq 5)12 and SET reactions of glycosyl halides showing either selective13a or nonselective13b substitution of the halide (eq 6).

Glycosyl cobaloximes have been employed as building blocks for KDO13a and as precursors for amino sugars.13c Tertiary alkyl cobaloximes(III) are limited to a few examples, but bridgehead positions are favorable sites for stable tertiary alkyl cobaloxime(III). A synthesis has been designed which takes advantage of the labile intermediate tertiary cobaloxime in the ring expansion of iodomethyl penicillin to a 3:2 mixture of exomethylene cepham to D2-cephem (eq 7).5

Vinyl triflates react with sodium cobaloxime(I) within 10 min at 0 °C in aqueous methanol to yield vinyl cobaloximes(III) (eq 8). Transformation of isomeric (E)- and (Z)-vinyl triflates results in stereoconvergence. Application of this methodology to alkynylvinyl triflates leads to s-butatrienyl- (eq 9) and s-enynylcobaloximes(III)14

Although arylation of halogenocobaloximes(III) by Grignard reagents is the method of choice for the synthesis of aryl cobaloximes, successful reactions of aryl bromides and cobaloxime(I) have been reported. An electron-withdrawing group in the para position (CF3, CO2Me) is required. Bromobenzene is unreactive (eq 10).15

1. (a) Schrauzer, G. N.; Deutsch, E.; Windgassen, R. J. JACS 1968, 90, 2441. (b) Schrauzer, G. N. Inorg. Synth. 1968, 11, 61. (c) Schrauzer, G. N.; Windgassen, R. J.; Kohnle, J. CB 1965, 98, 3324.
2. (a) Giese, B.; Hartung, J. CB 1992, 125, 1777. (b) Eckert, H.; Lenoir, D.; Ugi, I. JOM 1977, 141, C23. (c) Jensen, F. R.; Buchanan, D. H. CC 1973, 153. (d) Samsel, E. G.; Kochi, J. K. JACS 1986, 108, 4790. (e) Schrauzer, G. N.; Windgassen, R. J. JACS 1967, 89, 143. (f) Harrowven, D. C.; Pattenden, G. TL 1991, 32, 243. (g) Schrauzer, G. N.; Weber, J. H.; Beckham, T. M. JACS 1970, 92, 7078. (h) Toscano, P. J.; Brand, H.; Liu, S.; Zubieta, J. IC 1990, 29, 2101.
3. Schrauzer, G. N.; Kratel, G. CB 1969, 102, 2392.
4. Bhandal, H.; Pattenden, G.; Russell, J. J. TL 1986, 27, 2299.
5. Baldwin, J. E.; Adlington, R. M.; Kang, T. W. TL 1991, 32, 7093.
6. Eckert, H.; Schrauzer, G. N.; Ugi, I. T 1975, 31, 1399.
7. Bulkowski, J.; Cutler, A.; Dolphin, D.; Silverman, R. B. Inorg. Synth. 1980, 20, 127-134.
8. Giannotti, C.; Fontaine, C.; Septe, B. JOM 1974, 71, 107.
9. Schrauzer, G. N.; Deutsch, E. JACS 1969, 91, 3341.
10. Livermore, D. G. H.; Widdowson, D. A. JCS(P1) 1982, 1019.
11. Dodd, D.; Johnson, M. D.; Meeks, B. S.; Titchmarsh, D. M.; Duong, K. N. V.; Gaudemer, A. JCS(P2) 1976, 1261.
12. Shinozaki, H.; Ogawa, H.; Tada, M. BCJ 1976, 49, 775.
13. (a) Ghosez, A.; Göbel, T.; Giese, B. CB 1988, 121, 1807. (b) Branchaud, B. P.; Yu, G.-X. OM 1991, 10, 3795. (c) Giese, B.; Veit, A. SL 1990, 166.
14. (a) Stang, P. J.; Datta, A. K.; Dixit, V.; Wistrand, L. G. OM 1989, 8, 1020. (b) Stang, P. J.; Datta, A. K. JACS 1989, 111, 1358.
15. Brown, K. L.; Legates, R. JOM 1982, 233, 259.

Bernd Giese

University of Basel, Switzerland

Jens Hartung

University of Würzburg, Germany

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