Manganese-catalyzed Asymmetric Epoxidations

A breakthrough in the area of asymmetric epoxidation came at the beginning of the 1990s, when the groups of Jacobsen and Katsuki more or less simultaneously discovered that chiral Mn-salen complexes (15) catalyzed the enantioselective formation of epoxides [71, 72, 73], The discovery that simple achiral Mn-salen complexes could be used as catalysts for olefin epoxidation had already been made 

Entry Mn-salen (amount) Oxidant Additive131 Solvent Temp (°C) Yield (%) Ee (%) Ref. 

---

These reports sparked off an extensive study of metalloporphyrin-catalyzed asymmetric epoxidation, and various optically active porphyrin ligands have been synthesized. Although porphyrin ligands can make complexes with many metal ions, mainly iron, manganese, and ruthenium complexes have been examined as the epoxidation catalysts. These chiral metallopor-phyrins are classified into four groups, on the basis of the shape and the location of the chiral auxiliary. Class 1 are C2-symmetric metalloporphyrins bearing the chiral auxiliary at the... 

There are now many examples of the industrial use of manganese(lll) salen catalyzed asymmetric epoxidations. For example, the as5mmetric epoxidation of a chromene derivative was central to the S5mthesis of the potassium channel activator BRL 55834 (Figure 11.5). ... 

The report by Kochi and co-workers in 1986 that a (salen)manganese(lll) complex (Mn(salen) complex) was an efficient epoxidation catalyst for simple olefins <1986JA2309> quickly led to independent reports from the groups of Jacobsen <1990JA2801> and Katsuki <1990TL7345> that chiral Mn(salen) complexes could catalyze asymmetric epoxidation reactions. The reaction requires the use of a stoichiometric oxidant initially iodosylarenes were utilized, but it was quickly found that NaOCl was also successful. 

Chiral (salen)manganese(III)-catalyzed asymmetric epoxidation of alkenes. Enantio- and diastereo- selectivity depend strongly on the nature of the substrate ... 

SCHEME 33. Asymmetric epoxidation of olefins catalyzed by salen manganese complexes. 

In order to increase the yield and/or the enantioselectivity of the reaction, the reaction temperature and additives were examined. Although aziridination was found to proceed smoothly at 0 °C, the product was not obtained at lower temperatures. Katsuki and co-workers have reported that pyridine /V-oxide is an effective additive for the asymmetric epoxidation catalyzed by salen-manganese(IH) complexes [24], and applied these findings to the asymmetric aziridination of olefins with Phi = NTs [9f]. Thus, the addition of pyridine /V-oxide at 0°C improved the enantioselectivity and allowed the reaction to proceed even at -20 °C (Table 6.1). Other additives, such as 4-phenylpyridine IV-oxide, 4-methylmorphorine N-oxide and 1-methylimidazole were used in the place of pyridine JV-oxide, but positive effects were not observed. 

Asymmetric epoxidation (AE) of unfunctionalized alkenes catalyzed by chiral (salen)Mn(III) complex 38 (Scheme 2.13), developed by Jacobsen et al., is one of the most reliable methods [50]. As shown in Table 2.2, several different strategies have been formulated to immobilize Jacobsen s catalysts on inorganic supports [37-42]. Facilitation of catalyst separation, catalyst reuse, an increase in catalyst stability (e.g. minimization of the possibility of formahon of inachve g-oxo-manganese(lV) species [51a,b]) and sometimes improvement in enanhoselectivity are the main objectives of such research. Heterogenized Mn(salen) systems have recently been reviewed by Salvador et al. [51c] and Garcia et al. [5 Id]. Some selected cases are therefore described herein on the basis of the immobilizahon methods. 

The catalyhc asymmetric epoxidation of alkenes offers a powerful strategy for the synthesis of enantiomerically enriched epoxides. Among the several existing catalyhc methods, the asymmetric epoxidahon of unfunctionalized alkenes catalyzed by chiral Mn(lll)(salen) complexes such as homochiral [( N.N )-bis(3,5-di-tert-butylsalicylidene)-l,2-cyclohexanediamine]manganese(lll) chloride (22) (Figure 7.7), as developed by Jacobsen and coworkers, represents one ofthe most reliable methods [39]. 

Asymmetric epoxidation of unfunctionalized aUcenes catalyzed by chiral Mn(III)(salen) complexes has proven to be a useful solution-phase reaction [88]. To simplify product isolation and to avoid degradation of the Mn(salen) complex through formation of i-oxo-manganese(lV) dimers by spatial redistribution, the polymer-supported catalyst 112 was prepared by co-polymerization of complex 113, styrene 58, and divinylbenzene as a cross-linker (Scheme 20) [89]. As a stoichiometric oxidant, a combination of meta-chlor-operbenzoic acid (mCPBA) and N-methyl-morpholine N-oxide (NMO) in acetonitrile was used. Yields and rates of conversion were satisfactory for the epoxidation of styrene 58 and of methyl styrene, but only low enantioselectivities were obtained. Nevertheless, the catalyst retained its efficiency in terms of yields and enantioselectivities after repetitive use. Similar results have been described by other researchers [90]. 

The oxidation of saturated hydrocarbons in the presence of iron- or manganese-containing catalysts can be achieved by using a variety of oxidants including alkyl hydroperoxides, peroxycarboxylic acids, iodosyl-benzene, dihydrogen peroxide, and dioxygen (9-11). It has been shown that chiral iron- and manganese-porphyrin complexes catalyze the asymmetric epoxidation of unfunctionalized alkenes (75). Except for a number of experiments in which up to 96 % enantiomeric excess (ee) has been reported (16,17), in most epoxidation reactions with chiral porphyrins only a low to moderate enantiomeric excess of the product is obtained (18,19). In association with these catalysts, alkyl hydroperoxides and iodosylbenzene are often used as primary oxidants (18,19). 

Epoxidation of stilbenes and other alkenes occupies a great deal of attention. Asymmetric epoxidation is an industrially important method for synthesizing epoxides from readily available olefins. In particular, the use of coordination complexes of transition metals as catalysts is of abiding importance, as it proffers an effective possibility for the synthesis of enantiomericaHy pure compounds ((19, 20] references therein). The manganese(111) complex with a diamide ligand was found to catalyze both the epoxidation of (Z)- and ( )-sti]benes with high conversion and the oxidation of benzyl alcohol to benzaldehyde (Figure 2.3) [21]. 

Previous reviews have dealt with metal-catalyzed [93] and stoichiometric [94] oxidation of amines in a broad sense. This section will be limited to the selective oxidation of tertiary amines to N-oxides. Amine N-oxides are synthetically useful compounds [95, 96] and are frequently used as stoichiometric oxidants in osmium-[97-99] manganese- [100] and ruthenium-catalyzed [101,102] oxidations, as well as in other organic transformations [103-105]. Aliphatic tert-amine N-oxides are usefid surfactants [96] and are essential components in hair conditioners, shampoos, toothpaste, cosmetics, and so on [106]. Chiral N-oxides have been used in asymmetric catalysis involving metal-free catalytic transformations [107] as well as metal-catalyzed reactions where the N-oxide serves as a ligand [107, 108]. Chiral tertiary amine N-oxides were recently used as reagents in asymmetric epoxidation of a,(3-unsaturated ketones [109]. 

Kinetic resolutions. A chiral alcohol is obtained on. selective removal of one enantiomer by acetylation using a chiral analog 1 of DMAP, or by oxidation based on hydrogen transfer to acetone mediated by a Ru complex 2. Benzylic secondary alcohols are resolved by selective pivaloylation with optically activeA-pivaloyl-4-t-butylthiazolidine-2-thione. A kinetic resolution of sulfoxides is based on asymmetric oxidation with (i-PrO)4Ti-cumyl hydroperoxide in the presence of a tartrate ester. Kinetic resolution of 1,3-diarylallenes is realized by selective oxidation with NaClO catalyzed by a chiral (salen)manganese(III) complex, whereas asymmetric hydrolysis of terminal epoxides with the aid of a chiral (salen)cobalt(II) catalyst solves the problem of their accessibility. 

---