Salen catalysts

To date, a wide variety of structurally different chiral Mn(III)salen complexes have been prepared, of which only a handful have emerged as synthetically useful catalysts. By far the most widely used Mn(III)salen catalyst is the commercially available Jacobsen catalyst wherein R= -C4H8- and R = = i-Bu (Scheme 1.4.1). In... 

Ten years after Sharpless s discovery of the asymmetric epoxidation of allylic alcohols, Jacobsen and Katsuki independently reported asymmetric epoxidations of unfunctionalized olefins by use of chiral Mn-salen catalysts such as 9 (Scheme 9.3) [14, 15]. The reaction works best on (Z)-disubstituted alkenes, although several tri-and tetrasubstituted olefins have been successfully epoxidized [16]. The reaction often requires ligand optimization for each substrate for high enantioselectivity to be achieved. 

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%. 

An alternative preparation of aziridines reacts an alkene with iodine and chloramine-T (see p. 1056) generating the corresponding A-tosyl aziridine. Bromamine-T (TsNBr Na ) has been used in a similar manner." Diazoalkanes react with imines to give aziridines." Another useful reagent is NsN=IPh, which reacts with alkenes in the presence of rhodium compounds or Cu(OTf)2 to give N—Ns aziridines. Manganese salen catalysts have also been used with this reagent. ... 

Fueled by the success of the Mn (salen) catalysts, new forays have been launched into the realm of hybrid catalyst systems. For example, the Mn-picolinamide-salicylidene complexes (i.e., 13) represent novel oxidation-resistant catalysts which exhibit higher turnover rates than the corresponding Jacobsen-type catalysts. These hybrids are particularly well-suited to the low-cost-but relatively aggressive-oxidant systems, such as bleach. In fact, the epoxidation of trans-P-methylstyrene (14) in the presence of 5 mol% of catalyst 13 and an excess of sodium hypochlorite proceeds with an ee of 53%. Understanding of the mechanistic aspects of these catalysts is complicated by their lack of C2 symmetry. For example, it is not yet clear whether the 5-membered or 6-membered metallocycle plays the decisive role in enantioselectivity however, in any event, the active form is believed to be a manganese 0x0 complex <96TL2725>. 

Investigation of Deactivation of Co-Salen Catalysts in the Hydrolytic Kinetic Resolntion of... 

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... 

Recently, we have prepared an oligo(cyclooctene) snpported Co-salen catalyst (A), with the idea that the higher local concentration of Co-salen species in the macrocyclic framework would enhance the reactivity and enantioselectivity in the HKR reaction (18). 

Hydrolytic Kinetic Resolution (HKR) of epichlorohydrin. The HKR reaction was performed by the standard procedure as reported by us earlier (17, 22). After the completion of the HKR reaction, all of the reaction products were removed by evacuation (epoxide was removed at room temperature ( 300 K) and diol was removed at a temperature of 323-329 K). The recovered catalyst was then recycled up to three times in the HKR reaction. For flow experiments, a mixture of racemic epichlorohydrin (600 mmol), water (0.7 eq., 7.56 ml) and chlorobenzene (7.2 ml) in isopropyl alcohol (600 mmol) as the co-solvent was pumped across a 12 cm long stainless steel fixed bed reactor containing SBA-15 Co-OAc salen catalyst (B) bed ( 297 mg) via syringe pump at a flow rate of 35 p,l/min. Approximately 10 cm of the reactor inlet was filled with glass beads and a 2 pm stainless steel frit was installed at the outlet of the reactor. Reaction products were analyzed by gas chromatography using ChiralDex GTA capillary column and an FID detector. 

Spectroscopic evaluation of the catalysts. The UV-Vis spectra of the Jacobsen Co-salen catalysts were collected in the transmission mode on a CARY-3E UV-Vis spectrophotometer by dissolving the catalysts in epichlorohydria The Co K-edge (7709 eV) X-ray absorption near edge stracture, XANES, of Jacobsen s Co-salen catalyst was collected during the HKR reaction at beamline XIO-C at National Synchrotron Light Source (NSLS), Brookhaven National Lab, Upton, NY. 

Electrospray Ionization - Mass Spectrometry (ESI-MS). The Jacobsen s Co-salen catalysts dissolved in dichloromethane were pumped to the mass spectrometer system after dilution with methanol at a flow rate of 50 pi min and 600 scans were collected in 1 min. 

Recycling studies on Jacobsen s Co-OAc salen catalyst (without regeneration). The HKR of racemic epichlorohydrin (10 mmol) was performed in the presence of 0.5 mol% R,R-Jacobsen s Co-OAc salen catalyst and water (0.7 eq), producing S-epichlorohydrin and R-3-chloro 1,2-propane diol as the major products (eq. 1). 

Kim et al. (19) also observed that the ee of recovered epichlorohydrin was reduced to 17% in the second hydrolysis reaction with Jacobsen s Co-OAc salen catalyst, if the catalyst was not regenerated with acetic acid in air. Although they attributed the loss of enantioselectivity to the reduction of Co(lll) to Co(ll) salen complex after the HKR reaction, no spectroscopic evidence was provided. Therefore, we probed the catalyst by UV-Vis and XANES spectroscopy before and after the HKR reaction. 

Reaction conditions 10 mmol racemic epichlorohydrin (ECH), 0.7 eq. water, 0.5 mol% R,R-Jacobsen s Co-0 Ac salen catalyst, 120 pi chlorobenzene, 300 K reaction temperature. 

Effect of dimer formation on deactivation. Another possible mode of deactivation is formation of inactive Co dimers or oligomers. To test for these species, we examined the ESI-mass spectram of fresh and deactivated Co-salen catalysts in dichloromethane solvent (22). The major peak in the mass spectram occurred at m/z of 603.5 for both Jacobsen s Co(II) and Co(III)-OAc salen catalysts, whereas much smaller peaks were observed in the m/z range of 1207 to 1251. The major feature at 603.5 corresponds to the parent peak of Jacobsen s Co(II) salen catalyst (formula weight = 603.76) and the minor peaks (1207 to 1251) are attributed to dimers in the solution or formed in the ESI-MS. The ESI-MS spectrum of the deactivated Co-salen catalyst, which was recovered after 12 h HKR reaction with epichlorohydrin, was similar to that of Co(II) and Co(III)-OAc salen. Evidently, only a small amount of dimer species was formed during the HKR reaction. However, the mass spectram of a fresh Co(III)-OAc salen catalyst diluted in dichloromethane for 24 h showed substantial formation of dimer. The activity and selectivity of HKR of epichlorohydrin with the dimerized catalyst recovered after 24 h exposure to dichloromethane were similar to those observed with a fresh Co-OAc salen catalyst. Therefore, we concluded that catalyst dimerization cannot account for the observed deactivation. 

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