Salen catalyst, epoxide

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%. 

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>. 

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... 

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. 

More subtle arguments have been invoked to rationalize the dichotomous behavior of so-called second-generation Mn-salen catalysts of type 7 toward unfunctionalized and nucleophilic olefins. For example, higher yields and ee s are obtained with the (i ,S)-complex for the epoxidation of indene (8). However, JV-toluenesulfonyl-l,2,3,4-tetrahydropyridine (10) gave better results using the (R,/ -configuration. An analysis of the transition-state enthalpy and entropy terms indicates that the selectivity in the former reaction is enthalpy driven, while the latter result reflects a combination of enthalpy and entropy factors <00TL7053>. 

Many efforts have been made to develop salen catalysts for the epoxidation of unfunctionalized olefins, and such work has been well documented.93 Very recently, Ito and Katsuki94 proposed that the ligand of the oxo salen species is not planar, but folded as shown in Figure 4-7 (R/ / H, R2 = H, L = achiral axial ligand). This folded chiral structure amplifies asymmetric induction by the Mn-salen complex. This transition state proposed by Ito and Katsuki is not compatible with the proposal by Palucki et al.95 that the salen ligands of oxo species are planar. 

Stereoselective alkene epoxidations have been performed using the ionic liquid bmim PI (, in a biphase with dichloromethane, using a Mn-salen catalyst [10], as shown in Scheme 9.5. This gave yields in excess of 70% and enantiomeric... 

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%). 

Week et al. [65] further reported the Co salen complex supported on norbomene polymers (23, 24) with stable phenylene-acetylene linker (Figure 8). The polymer-supported salen catalysts were investigated for HKR of the racemic terminal epoxides that showed outstanding catalytic activities and comparable selectivities to the original catalysts reported by Jacobsen. However, the polymeric catalyst was recycled only once after its precipitation with diethylether as the catalyst became less soluble and less reactive in subsequent catalytic... 

Kim et al. [67] recently reported the synthesis of heterometallic chiral polymer (salen) Co-(Al, Ga, ln)Cl3 complexes 26-32 (Figure 10) and their use in the HKR of racemic epoxides. Polymeric salen catalysts showed very high reactivity and enantioselectivity at substantially lower catalyst loadings for the asymmetric ring opening of terminal epoxide to obtain the enantio-enriched products. The performance of catalysts is retained on multiple-use and do not suffer the problems of solubility and deactivation (Scheme 5). 

Scheme 5. HKR of terminal epoxides catalyzed by polymeric salen catalysts 26-32.

Various other chromene derivatives 176a-d could be epoxidized with Katsuki s Mn-salen catalyst 173d using either H2O2 or TMS2O2 as oxidant. With this catalytic system several axial ligands (none, 7V-methylimidazole, pyridine TV-oxide) and additives (none. 

In the realm of hydrolytic reactions, Jacobsen has applied his work with chiral salen complexes to advantage for the kinetic resolution of racemic epoxides. For example, the cobalt salen catalyst 59 gave the chiral bromohydrin 61 in excellent ee (>99%) and good yield (74%) from the racemic bromo-epoxide 60. The higher than 50% yield, unusual for a kinetic resolution, is attributed to a bromide-induced dynamic equilibrium with the dibromo alcohol 62, which allows for conversion of unused substrate into the active enantiomer <99JA6086>. Even the recalcitrant 2,2-disubstituted epoxides e.g., 64) succumbed to smooth kinetic resolution upon treatment with... 

Chiral (salen) Mn(III) complexes have been found to be highly enantioselective for the asymmetric epoxidation of conjugated cis-disubstituted and trisubstituted oleftns[10]. The increasing interest towards this reaction brought some authors to develop the heterogeneous chiral salen catalysts. However, to date three kinds of approach have been adopted for the immobilization of chiral salens (1) Chiral Mn salen complexes were supported on polymers[l 1], (2) The encapsulation of salen complex using ship-in-bottle method was... 

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