Co-salen catalysts

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%. 

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). 

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. 

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. 

Table 43.2. Effect of counterions on the deactivation of Jacobsen s Co-salen catalyst...

Toward HKR in a continuous reactor. Although multimeric homogeneous soluble Co-salen catalysts exhibit high activity and selectivity in the HKR reaction, they caimot be utilized in a fixed-bed reactor without some form of immobilization. Thus, it is highly desirable to synthesize an insoluble supported Co-salen catalyst that can be used in a continuous reactor under HKR conditions. We have recently prepared an SBA-15 supported Co-salen catalyst (B) that has been tested in a fixed-... 

In order to assess whether intramolecular cooperativity could occur within the dendrimeric [Co(salen)]catalyst the HKR of racemic l-cyclohexyl-l,2-ethenoxide was studied at low catalyst concentrations (2xl0 " M). Under these conditions the monomeric [Co(salen)] complex showed no conversion at all, while the dendritic [G2]-[Co(salen)]catalyst gave an impressive enantiomeric excess of 98% ee of the epoxide at 50% conversion. Further catalytic studies for the HKR with 1,2-hexen-oxide revealed that the dendritic catalysts are significantly more active than a dimeric model compound. However, the [Gl]-complex represents already the maximum (100%) in relative rate per Go-salen unit, which was lower for higher generations [G2] (66%) and [G3] (45%). 

Figure 4. Structure of fluorous chiral Co(salen) catalysts 6-8.

Davis et al. [66] developed an oligo(cyclooctene)-supported Co-OAc salen complex 25 (Figure 9) which efficiently catalyzed HKR of epichlorohydrin. The catalyst was recycled many times with negligible deactivation. The oligomeric complex was found to be 25 times more reactive than monomeric Co-salen. This study also gives possible modes of deactivation of Jacobsen s Co-salen catalyst during HKR of epichlorohydrin by spectroscopy, combined with recycling studies. 

Jain, S. Zheng, X. Jones, C. W. Week, M. Davis, R. J. (2007) Importanee of counterion reaetivity on the deactivation of Co-salen catalysts in the hydrolytie kinetic resolution of epiehlorohydrin, Inorg. Chem., 46 8887-8896. 

Kervinen et al. (2005) investigated a homogeneous catalytic reaction, namely, the oxidation of veratryl alcohol to its aldehyde in the liquid phase. In this case, UV-vis spectroscopy, performed by immersing a fiber probe in the reacting medium, allowed detection of changes in the Co (salen) catalyst as well as monitoring of product formation. 

Figure 4.30 The PAMAM dendrimer-bound chiral [Co(salen)] catalysts for asymmetric ring opening of epoxides.

Jacobsen disclosed a chiral Co(salen) catalyst that promoted the hydrolytic kinetic resolution (HKR) of terminal epoxides [40]. Remarkably low levels of the Co(salen)OAc complex 12 effected enantioselective epoxide hydrolysis to afford mixtures of the unreacted epoxide and the ring-opened diol. Controlling the amount of water in the HKR allowed either of these chiral products to be generated in high enantiopurity (Tables 3 and 4) [41]. Significant differences in vola-... 

The Co(salen) catalyst is remarkably insensitive to the steric properties of terminal epoxide substrates, as substituents ranging from methyl to cyclohexyl to ferf-butyl groups are accommodated in the kinetic resolution. Propylene oxide presented an impressive illustration of catalyst enantiocontrol, where a kj i exceeding 400 was estimated for this substrate. This epoxide served to further emphasize the synthetic utiHty of this process, as the HKR of 1 mole of propylene oxide proceeded efficiently with catalyst that had been recycled from previous kinetic resolutions (Scheme 18) The HKR of propylene oxide has also been effected on a multi-hundred kilogram scale in the pilot plant at ChiRex. 

In 2002, Ley reported the application of resin-bound reagents and polymers towards the synthesis of carpanone [57]. In the final steps towards carpanone, a resin-bound Co(salen) catalyst was used to give the desired intermediate along with the formation of a small amount of aldehyde by-product. To remove this byproduct, a resin-bound tris-amine scavenger was used, yielding the desired product in high purity (Scheme 8.42). 

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