Mechanistic Study of the Jacobsen Asymmetric Epoxidation of Indene

Abstract

The asymmetric epoxidation of indene using aqueous NaOCl, catalyzed by Jacobsen's chiral manganese salen complex, provides indene oxide in 90% yield and 85-88% enantioselectivity. The axial ligand, 4-(3-phenylpropyl)pyridine N-oxide (P(3)NO), increases the rate of epoxidation without affecting enantioselectivity and also stabilizes the catalyst. These two effects afford a reduction in catalyst loading to <1%. The turnover-limiting step in the catalytic cycle has been determined to be the oxidation of the manganese catalyst, based on reaction orders of 0 in indene and 1 in catalyst and also based on the dependence of the rate on the hypochlorite concentration. In the presence of the ligand P(3)NO, this rate-limiting oxidation occurs in the organic phase with HOCl as oxidant, as shown by the dependence of the rate on the NaOH concentration. P(3)NO assists the transport of HOCl to the organic layer as demonstrated by titration studies and by measuring the rates of oxidation of a redox indicator, diphenylbenzidine. On the other hand, stirring speed studies indicate that, in the absence of the ligand, oxidation occurs at the interface. Thus, the axial ligand plays at least two roles in the epoxidation of indene: it stabilizes the catalyst, presumably by ligation, and it increases the epoxidation reaction rate by drawing the active oxidant, HOCl, into the organic layer.

Polymer-supported salen complexes for heterogeneous asymmetric synthesis: Stability and selectivity

“…This decomposition severely limits the potential utility of heterogenized salen complexes for use in epoxidation reactions and limits the extent to which either the heterogeneous or homogeneous catalyst can be recycled for such reactions. Additionally, the observed decomposition suggests that other routes 42,53 beyond the commonly cited inactivation process involving a Mn IV dimer 39 occur in solution that prevent recycle of the homogeneous catalyst for this reaction.…”

“…39,40 In addition, various authors have alluded to a bleaching or decomposition of the catalyst during reaction without providing further details. 41,42 For the heterogeneous versions of the catalyst, while tethering these moieties onto a polymeric support would prevent dimerization of the active complex, these heterogeneous catalysts have had only moderate success in terms of their enantioselective performance. 13,15,43,44 Their decreased enantioselectivity is likely due to an interference between the macrocyclic structure of the ligand that governs chiral discrimination and the proximal structure of the support.…”

“…42,53 In addition, various reports indicate that the use of donor ligands (substituted pyridine-N-oxides) slightly enhance the stability of the Mn-salen catalyst during the epoxidation reaction. 42,48,54,55 Presently, no mechanistic details for this degradation or the basis for the use of a stabilizing ligand have been reported.…”

“…42,53 In addition, various reports indicate that the use of donor ligands (substituted pyridine-N-oxides) slightly enhance the stability of the Mn-salen catalyst during the epoxidation reaction. 42,48,54,55 Presently, no mechanistic details for this degradation or the basis for the use of a stabilizing ligand have been reported. Our presented observations regarding the lack of stability for the homogeneous ligand, as well as its heterogeneous analogue, during exposure to NaOCl provide additional information as to the processes occurring in solution during epoxidation (beyond the commonly cited dimerization process 39 ) that prevent significant recovery and reuse of the homogeneous catalyst.…”

A Catalytic Langmuir Film as a Model for Heterogeneous and Homogeneous Catalytic Processes

“…Thus, the small increase in reactivity can not be ascribed to a change in the molecular orientation in the Langmuir film, but should be simply related to the variation of the average molecular density. Because the epoxidation of cinnamyl alcohol should be roughly first order in catalyst concentration, as was demonstrated in the bulk for indene, [19] we can assume that the reaction along the monolayer is also first-order in the average catalyst surface density. Therefore, the apparent rate of reaction should be proportional to the surface molecular density of 1.…”