Kinetic resolution, terminal epoxides

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. - ... 

Two recent reports described addition of nitrogen-centered nucleophiles in usefully protected fonn. Jacobsen reported that N-Boc-protected sulfonamides undergo poorly selective (salen) Co-catalyzed addition to racemic epoxides. However, by performing a one-pot, indirect kinetic resolution with water first (HKR, vide infra, Table 7.1) and then sulfonamide, it was possible to obtain highly enantiomer-ically enriched addition products (Scheme 7.39) [71]. These products were transformed into enantioenriched terminal aziridines in straightforward manner. 

In sharp contrast, Bartoli showed that the (salen) Co catalyst system could be applied to the kinetic resolution of terminal epoxides with unprotected tert-butyl carbamate as nucleophile with extraordinarily high selectivity factors (Scheme 7.40) [72]. Excellent yields and selectivities are also obtained with use of ethyl, Cbz,... 

Although several interesting nitrogen-centered nucleophiles have been developed with ARO reactions of epoxides (vide supra), kinetic resolutions with such reagents are unlikely to be of practical value for the recovery of enantioenriched terminal epoxides. This is due to the fact that these nucleophiles are too valuable to be discarded in a by-product of the resolution, are generally not atom-economical, and, particularly in the case of azide, may represent safety hazards. 

The principle cost determinant in typical hydrolytic or phenolic resolutions is the cobalt catalyst, despite the relatively low catalyst loadings used in most cases and the demonstrated recyclability with key substrates. From this standpoint, recently developed oligomeric (salen)Co complexes, discussed earlier in this chapter in the context of the hydrolytic desymmetrization of meso-epoxides (Scheme 7.16), offer significant advantages for kinetic resolutions of racemic terminal epoxides (Table 7.3) [29-31]. For the hydrolytic and phenolic kinetic resolutions, the oligo-... 

One way of overcoming these problems is by kinetic resolution of racemic epoxides. Jacobsen has been very successful in applying chiral Co-salen catalysts, such as 21, in the kinetic resolution of terminal epoxides (Scheme 9.18) [83]. One enantiomer of the epoxide is converted into the corresponding diol, whereas the other enantiomer can be recovered intact, usually with excellent ee. The strategy works for a variety of epoxides, including vinylepoxides. The major limitation of this strategy is that the maximum theoretical yield is 50%. 

The asymmetric ring opening (ARO) of racemic terminal epoxides with H2O via hydrolytic kinetic resolution provides an efficient synthetic route to prepare optically pure terminal epoxides. The dimeric type chiral Co(salen)AlX3 complex has great potential to catalyze HKR of terminal epoxides in a highly reactive and enantioselective manner in comparison to their monomeric analogy. 

The hydrolytic kinetic resolution of terminal epoxides catalyzed by the monomer la and dimer lb... 

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... 

S,12S)-2,12-Diacetoxytridecane (17) is a component of the female pheromone of pea midges (Contarinia pisi). Kitching synthesized 17 as shown in Scheme 28 by employing Jacobsen s hydrolytic kinetic resolution of terminal epoxides with a (salen)Co(OAc) complex, (S,S)-B [46]. By this reaction bis-... 

M. Tokunaga, J. F. Larrow, F. Kakiuchi, E. N. Jacobsen, Asymmetric Catalysis with Water Efficient Kinetic Resolution of Terminal Epoxides by Means of Catalytic Hydrolysis, Science 1997, 2T7, 936-938, and references cited therein. 

Covalent attachment chiral Co(salen) complexes to polystyrene and silica gave efficient and highly enantioselective catalysts for the hydrolytic kinetic resolution (HKR) of terminal epoxides, including epichlorohydrin. These systems provide practical solutions to difficulties with the isolation of reaction products from the HKR. Removal of the supported catalyst by filtration and repeated recycling was demonstrated with no loss of reactivity or enantioselectivity. The immobilised catalysts have been adapted to a... 

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). 

Kinetic resolution of racemic terminal epoxide with water (HKR) is an attractive strategy for the synthesis of valuable enantiopure terminal epoxide and corresponding diol. Easy availability of terminal epoxides at cheaper price and water as sole reagent with a recoverable chiral catalyst makes this solvent free protocol very attractive for its commercial exploitation [53, 54]. Both terminal epoxides and respective diols in their chirally pure form have wider applications in academics and industry [48, 50]. For the efficient resolution the reaction rates of the two enantiomers must be unequal and the reaction must be stopped when only one enantiomer reacts to give a maximum of 50% product leaving behind the other enantiomer unreacted. 

Kim et al. [67], used the self-polymerized heterometallic polymeric salen complexes 26-32 as efficient catalysts for kinetic resolution of terminal epoxides with phenols to give a-aryloxy alcohols in high yields (38-43%) and ee (92-99%) (Scheme 17). These catalysts were recycled up to three times without any loss in their performance. 

Tokimaga, M. Larrow, J. F. Kakiuchi, F. Jacobsen E. N. (1997) Asymmetric catalysis with water Efficient kinetic resolution of terminal epoxides by means of catalytic hydrolysis., Science, 111 936-938. 

Kureshy, R. I. Singh, S. Khan, N. H. Abdi, S. H. R. Ahmad, I. Bhatt, A. Jasra R. V. (2005) Improved catalytic activity of homochiral dimeric cobalt salen complex in hydrolytie kinetic resolution of terminal racemic epoxides.. Chirality, 17 590-594. 

Cavazzini, M. Quid, S. Pozzi, G. (2002) Hydrolytic kinetic resolution of terminal epoxides eatalyzed by fluorous chiral Co(salen) complexes. Tetrahedron 58 3943-3949. 

Shepperson, L Cavazzini, M. Pozzi, G. Quici, S. (2004) Fluorous biphasic hydrolytic kinetic resolution of terminal epoxides, J. Fluor. Chem., 125 175-180. 

Annis, D. A. Jaeobsen, E. N. (1999) Polymer supported ehiral Co(salen) complexes synthetie applieations and mechanistic investigations in the hydrolytic kinetic resolution of terminal epoxides., Y. Am. Chem. Soc., 121 4147-4154. 

The importance of hydrolytic kinetic resolution (HKR) in providing a wide range of highly enantiomerically enriched terminal mono- and bis epoxides has been showed by the conversion of such epoxides efficiently to some important insect pheromones. 1 51... 

Enantiomer-differentiating co-polymerization of terminal epoxides is achieved by chiral chromium and cobalt complexes. Jacobsen etal. reported the co-polymerization of 1-hexene oxide with GO2 by using complex 35a. The reaction proceeds with kinetic resolution at 90% conversion, the unreacted epoxide is found to be enriched in the (i )-enantiomer of 90% ee. Detailed information about the resultant polymer, however, is not described. As discussed in the previous section, chiral cobalt-salen complex 34c co-polymerizes PO and GO2 (Table 3). When 34c with /r<3 / j--(li ,2i )-diaminocyclohexane backbone is applied to the co-polymerization, (A)-PO is consumed preferentially over (i )-enantiomer with a of 2.8 to give optically active PPG (Equation (8)). In a similar manner, a binary catalyst system, 34d/Bu4NGl, preferentially consumes (A)-PO over R)-PO with = 2.8-3.5. ... 

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