Sodium Hypochlorite-N,N-Bis(3,5-di-t-butylsalicylidene)-1,2-cyclohexanediaminomanganese(III) Chloride1

(NaOCl)

[7681-52-9]  · ClNaO  · Sodium Hypochlorite-N,N-Bis(3,5-di-t-butylsalicylidene)-1,2-cyclohexanediaminomanganese(III) Chloride  · (MW 74.44) (R,R)-(1)

[138124-32-0]  · C36H52ClMnN2O2  · Sodium Hypochlorite-N,N-Bis(3,5-di-t-butylsalicylidene)-1,2-cyclohexanediaminomanganese(III) Chloride  · (MW 635.29) (S,S)-(1)

[135620-04-1]

(catalytic system for enantioselective epoxidation of unfunctionalized alkenes2)

Physical Data: NaOCl: see Sodium Hypochlorite. (1): mp 330-332 °C.

Solubility: (1) freely sol CH2Cl2, t-butyl methyl ether, acetonitrile, ethyl acetate.

Form Supplied in: both enantiomers of (1) are commercially available as brown powders, 98%; synthetic preparations may contain up to one solvated molecule of ethanol or DMF for each manganese.

Analysis of Reagent Purity: (salen)MnIII complexes are paramagnetic and do not provide readily interpretable NMR data. (1): Rf = 0.63 (SiO2, ethanol); purity may be established by elemental analysis.

Preparative Methods: over 100 chiral manganese(III) salen complexes have been reported;1 the general procedure for their preparation involves condensation of a 1,2-diamine with 2 equiv of a salicylaldehyde derivative, followed by addition of Mn(OAc)2 in the presence of air.3 Yields of (salen)MnIII complexes usually exceed 90%.

Purification: (1) can be recrystallized from toluene or CH2Cl2/heptane. The solvent content of (1) and related complexes does not influence their effectiveness as epoxidation catalysts,4 but heating to >80 °C for 3 h under vacuum results in liberation of solvated molecules.

Handling, Storage, and Precautions: (1) is sensitive to acid, but indefinitely stable to air, moisture, and light.

Epoxidation Method.

Epoxidation of a variety of conjugated and nonconjugated alkenes may be effected in a biphasic reaction system consisting of aqueous bleach at pH &egt; 9.5 and an organic phase bearing catalytic levels of a soluble manganese(III) complex.4,5 The ideal pH range appears to be 10.5-11.5 for most applications, with nonwater-miscible solvents such as CH2Cl2, t-butyl methyl ether, or ethyl acetate as the organic solvent. At pH <= 11.5, no phase transfer catalysts are necessary for epoxidation to occur, due to the presence of significant equilibrium concentrations of HOCl.5 At low pH, equilibrium levels of Cl2 can produce chlorinated byproducts. Reactions with alkenes are carried out in air, without the need for precautions to exclude moisture or trace impurities. The substrate and catalyst are dissolved in the organic solvent and combined with the bleach solution at 0 °C or room temperature. Catalyst turnover numbers and product yields may be improved in the epoxidation of certain substrates by the addition of substoichiometric levels of a pyridine N-oxide derivative (Table 1).3a,6 Isolation of the epoxide is accomplished by separation of the organic phase and purification by distillation, crystallization, or chromatography.

Substrate Scope.

Best results in the (salen)MnIII-catalyzed epoxidation reaction have been obtained with cis-disubstituted, conjugated alkenes (Table 1). Epoxidation of 2,2-dimethylchromene derivatives occurs with especially high selectivity (&egt;97% ee).7 trans-Disubstituted alkenes are epoxidized with low selectivity (20-50% ee), as are simple alkyl-substituted alkenes.

Mechanistic Considerations.

A stepwise mechanism involving a nonpolar intermediate has been proposed for the oxygen atom transfer event in (salen)MnIII-catalyzed epoxidations (eq 1).6a,8 Consistent with this proposal, acyclic cis-alkenes afford mixtures of cis- and trans-epoxides, and conjugated alkenes are 1-2 orders of magnitude times more reactive than isolated alkenes.1 In the case of dienes and enynes, the trans-epoxide can in fact constitute the major product.7

In the case of 1,2-disubstituted alkenes, the nonstereospecificity of the epoxidation reaction results in formation of diastereomeric epoxides. In contrast, for terminal alkenes the trans pathway results in partitioning to enantiomers. Thus, diminished enantioselectivity observed in the epoxidation of terminal alkenes such as styrene (50-70% ee) relative to sterically similar cis-disubstituted alkenes can be attributed to enantiomeric leakage due to the trans pathway. Suppression of this pathway has not been accomplished successfully, and synthetically useful enantioselectivities with terminal alkenes have not yet been achieved using the chiral (salen)MnIII systems.


1. Jacobsen, E. N. in Catalytic Asymmetric Synthesis; Ojima, I., Ed.; VCH: New York, 1993; in press.
2. (a) Zhang, W.; Loebach, J. L.; Wilson, S. R.; Jacobsen, E. N. JACS 1990, 112, 2801. (b) Jacobsen, E. N.; Zhang, W.; Muci, A. R.; Ecker, J. R.; Deng, L. JACS 1991, 113, 7063.
3. (a) Boucher, L. J. Inorg. Nucl. Chem. 1974, 36, 531. (b) Deng, L.; Jacobsen, E. N. JOC 1992, 57, 4320.
4. Zhang, W.; Jacobsen, E. N. JOC 1991, 56, 2296.
5. Banfi, S.; Montanari, F.; Quici, S. JOC 1989, 54, 1850.
6. (a) Samsel, E. G.; Srinivasan, K.; Kochi, J. K. JACS 1985, 107, 7606. (b) Irie, R.; Ito, Y.; Katsuki, T. SL 1991, 265.
7. Lee, N. H.; Muci, A. R.; Jacobsen, E. N. TL 1991, 32, 5055.
8. Lee, N. H.; Jacobsen, E. N. TL 1991, 32, 6533.

Eric N. Jacobsen

Harvard University, Cambridge, MA, USA



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