Mn-salen catalysts

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. 

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>. 

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>. 

Miyafuji and Katsuki95 reported the desymmetrization of meso-tetrahydrofuran derivatives via highly enantioselective C-H oxidation using Mn-salen catalysts. The optically active product lactols (up to 90% ee) are useful chiral building blocks for organic synthesis (Scheme 8-48). 

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... 

The geometries and spin multiplicities of models of the Mn -salen catalyst and the Mn -oxo intermediate have been studied using DFT. The Mn complexes have quintet ground states, while the nature of the salen ligand influences whether quintet, triplet, or singlet ground states are lowest in energy for the Mn -oxo intermediates. 

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 combination with H2O2 (salen)Mn(III) complexes 173a, b, i-n have also been employed by Jacobsen and coworkers as catalysts for the asymmetric oxidation of sulfides to sulfoxides, without a need for additives. From the structurally and electronically different Mn-salen catalysts screened, 173i turned out to be the most active and selective one (equation 58) . While dialkyl sulfides underwenf uncafalyzed oxidation with H2O2, aryl alkyl sulfides were oxidized only slowly compared wifh fhe cafalyzed pathway. Using... 

Mn-salen catalyst 173b or 173c, (ligand-additive), H202... 

These catalysts, 11-13, show good enantioselectivity ranging from 80 to 95% ee in the epoxidation of conjugated cfs-di- and tri-substituted olefins. Epoxidation of "good substrates such as 2,2-dimethylchromene derivatives proceeds with excellent enantioselectivity (>95% ee). Since the results obtained with these first-generation Mn-salen catalysts have been reviewed [21,33], only typical examples are shown in Table 6B.1. These reactions are usually carried out in the presence of donor ligand [34] such as 4-phenylpyridine A -oxide with terminal oxidants such as iodosylbenzene and sodium hypochlorite as described above. However, the use of some other terminal oxidants under well-optimized conditions expands the scope of the Mn-salen-... 

TABLE 6B.1. Epoxidation of Conjugated Olefins With the First-Generation Mn-salen Catalyst... 

The highest % ee reported with the first generation Mn-salen catalysts. 

The syntheses of most chiral Mn-salen complexes are simple, and thus their recovery and reuse have not been studied extensively. Only a few studies of epoxidation with a polymer-bound Mn-salen complex or a Mn-salen complex embedded in nano-porous materials as catalyst has been performed. It has been disclosed, however, that the microenvironment provided by the macromolecule adversely affects the asymmetric induction by the Mn-salen catalyst to a considerable extent although reuse of the catalysts for several cycles are realized [68]. 

In connection with the study on aerobic enantioselective epoxidation, /V,A - bis(3-oxobutyl-idene)diaminatomanganese(III) complex (25) is reported to be an effective catalyst for the reaction (Scheme 6B.24) [69]. It is noteworthy that epoxidations using 25 as the catalyst show higher enantioselectivity in the absence of a donor ligand rather than that in the presence of the ligand, which is different from the reaction using Mn-salen catalyst 22 (vide supra). This reaction... 

The use of Mn-salen catalysts for asymmetric epoxidation has been reviewed.30 Oxo(salen)manganese(V) complexes, generated by the action of PhIO on the corresponding Mn(III) complexes, have been used to oxidize aryl methyl sulfides to sulfoxides.31 The first example of C—H bond oxidation by a (/i-oxo)mangancsc complex has been reported.32 The rate constants for the abstraction of H from dihydroanthracene correlate roughly with O—H bond strengths. 

The Jacobsen Epoxidation allows the enantioselective formation of epoxides from various -substituted olefins by using a chiral Mn-salen catalyst and a stoichiometric oxidant such as bleach. 

Research groups at Sepracor53 54 and Merck50-52 independently developed similar strategies to access (lS)-amino-(2R)-indanol. Both processes used Jacobsen s Mn-(salen) catalyst (MnLCl, 2g)42-44,55 for indene epoxidation, followed by chirality transfer of the C-0 bond of indene oxide 26 to obtain enantiopure (15)-amino-(2/f)-indanol (Scheme 24.2). 

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