Hydrolytic kinetic resolution, epoxides synthesis

The hydrolytic kinetic resolution (HKR) of terminal epoxides using Co-salen catalysts provides a convenient route to the synthesis of enantioemiched chiral compounds by selectively converting one enantiomer of the racemic mixture (with a maximum 50% yield and 100% ee) (1-3). The use of water as the nucleophile makes this reaction straightforward to perform at a relatively low cost. The homogeneous Co(III) salen catalyst developed by Jacobsen s group has been shown to provide high... 

A very successful example for the use of dendritic polymeric supports in asymmetric synthesis was recently described by Breinbauer and Jacobsen [76]. PA-MAM-dendrimers with [Co(salen)]complexes were used for the hydrolytic kinetic resolution (HKR) of terminal epoxides. For such asymmetric ring opening reactions catalyzed by [Co(salen)]complexes, the proposed mechanism involves cooperative, bimetallic catalysis. For the study of this hypothesis, PAMAM dendrimers of different generation [G1-G3] were derivatized with a covalent salen Hgand through an amide bond (Fig. 7.22). The separation was achieved by precipitation and SEC. The catalytically active [Co "(salen)]dendrimer was subsequently obtained by quantitative oxidation with elemental iodine (Fig. 7.22). 

Much activity continues to be centered around the preparation of enantioenriched epoxides using chiral Co(III)-, Mn(III)- and Cr(III)-salen complexes, particularly in the area of innovative methods. A recent brief review <02CC919> focuses on the synthesis, structural features, and catalytic applications of Cr(III)-salen complexes. In an illustrative example, Jacobsen and coworkers <02JA1307> have applied a highly efficient hydrolytic kinetic resolution to a variety of terminal epoxides using the commercially available chiral salen-Co(III) complex 1. For example, treatment of racemic m-chlorostyrene oxide (2) with 0.8 mol% of catalyst 1 in the presence of water (0.55 equiv) led to the recovery of practically enantiopure (> 99% ee) material in 40% yield (maximum theoretical yield = 50%). This method appears to be effective for a variety of terminal epoxides, and the catalyst suffered no loss of activity after six cycles. 

Schaus, S. E., Brandes, B. D., Larrow, J. F., Tokunaga, M., Hansen, K. B., Gould, A. E., Furrow, M. E., Jacobsen, E. N. Highly Selective Hydrolytic Kinetic Resolution of Terminal Epoxides Catalyzed by Chiral (salen)Colll Complexes. Practical Synthesis of Enantioenriched Terminal Epoxides and 1,2-Diols. J. Am. Chem. Soc. 2002, 124, 1307-1315. 

S. E. Schaus, B. D. Brandes, J. F. Larrow, M. Tokunaga, K. B. Hansen, A. E. Gould, M. E. Furrow, E. N. Jacobsen, Highly selective hydrolytic kinetic resolution of terminal epoxides cataly zed by chiral (salen)Co complexes. Practical synthesis of enantioenriched termmal epoxides and... 

The synthesis is a catalogue of modern asymmetric catalytic methods. The epoxide 25 was resolved by a hydrolytic kinetic resolution (chapter 28) using a synthetic asymmetric cobalt complex. The asymmetric Diels-Alder reaction (chapter 26) was catalysed by a synthetic chromium... 

The hydrolytic kinetic resolution addressed a long-standing problem in enan-tioselective epoxide synthesis. The ability to access almost any terminal epoxide or 1,2-diol in high enantiopurity greatly expanded the chiral pool of compounds available for asymmetric synthesis. Equally important was the demonstration of practicality and efficiency that renders the ARO of a racemic mixture a synthetically viable approach. 

In particular, for the synthesis of optically pure chemicals, several immobilization techniques have been shown to give stable and active chiral heterogeneous catalysts. A step further has been carried out by Choi et al. [342] who immobilized chiral Co(III) complexes on ZSM-5/Anodisc membranes for the hydrolytic kinetic resolution of terminal epoxides. The salen catalyst, loaded into the macroporous matrix of Anodise by impregnation under vacuum, must exit near the interface of ZSM-5 film to contact with both biphasic reactants such as epoxides and water. Furthermore, the loading of chiral catalyst remains constant during reaction because it cannot diffuse into the pore channel of ZSM-5 crystals and is insoluble in water. The catalytic zeolite composite membrane obtained acts as liquid-liquid contactor, which combines the chemical reaction with the continuous extraction of products simultaneously (see Figure 11.28) the... 

Jacobsen s hydrolytic kinetic resolution of epoxides catalyzed by a Co(salen) catalyst analogous to the one used for asymmetric epoxidation has brought a considerable advance to the use of epoxides. Indeed, these substrates are among the most useful reagents in organic synthesis. One of the two epoxide enantiomers is selectively opened by a nucleophile (including water), which leads to both the terminal epoxide and the functional alcohol in quantitative yields (i.e. 50% of each) and more than 98 e.e. for both products. This system has been applied industrially by Rhodia on ton-scales for hydrolysis of propylene oxide and epichlorhydrin. - ... 

Paddon-Jones, G.C., McErlean, C.S.P., Hayes, P., Moore, C.J., Konig, W.A. and Kitching, W. (2001) Synthesis and stereochemistry of some bicydic y-lactones from parasitic wasps (Hymenoptera Braconidae). Utility of hydrolytic kinetic resolution of epoxides and palladium(II)-catalyzed hydroxycyclization[Pg.360]

Manoj, K.M., Archelas, A., Baratti, J. and Furstoss, R. (2001) Microbiological transformations. Part 45. A green chemistry preparative scale synthesis of enantiopure building blocks of Eliprodil elaboration of a high substrate concentration epoxide hydrolase-catalyzed hydrolytic kinetic resolution process. Tetrahedron, 57,695-701. 

Scheme 2.15 gives some examples of the use of epoxide hydrolases in organic synthesis. Entries 1 to 3 are kinetic resolutions. Note that in Entry 1 the hydrolytic product is obtained in high e.e., whereas in Entry 2 it is the epoxide that has the highest e.e. In the first case, the reaction was stopped at 18% conversion, whereas in the second case hydrolysis was carried to 70% completion. The example in Entry 3 has a very high E (> 100) and both the unreacted epoxide and diol are obtained with high e.e. at 50% conversion. Entry 4 shows successive use of two separate EH reactions having complementary enantioselectivity to achieve nearly complete... 

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