Alkene epoxidation catalytic cycle

The N-alkylation reaction represents a bifurcation of the normal alkene epoxidation reaction cycle and, therefore, N-alkylation is a suicide event that leads to catalytic inhibition in the native system. With synthetic tetraarylporphyrins that mimic the N-alkylation reaction, the use of halogen-substituted catalysts that are stable toward oxidative degradation (26, 27) provide the most useful model systems because the heme model remains intact for a significantly greater number of turnovers than the partition number. The partition number is the ratio of epoxidation cycles to N-alkylation cycles, i.e., N-alkyl porphyrins are formed before the heme is oxidatively destroyed. 

Other metals can also be used as a catalytic species. For example, Feringa and coworkers <96TET3521> have reported on the epoxidation of unfunctionalized alkenes using dinuclear nickel(II) catalysts (i.e., 16). These slightly distorted square planar complexes show activity in biphasic systems with either sodium hypochlorite or t-butyl hydroperoxide as a terminal oxidant. No enantioselectivity is observed under these conditions, supporting the idea that radical processes are operative. In the case of hypochlorite, Feringa proposed the intermediacy of hypochlorite radical as the active species, which is generated in a catalytic cycle (Scheme 1). 

Figure 13.5 Proposed catalytic cycle for the epoxidation of alkenes with H202 by H3PW12O40. (From Ishii, Y. et al J. Org. Chem., 53, 3587, 1988.)...

Figure 13.8 Proposed catalytic cycle for the epoxidation of alkenes by [jc-C5H5NC16H33]3[P04(WO)4] catalyst coupled with the 2-ethylanthraquinone/2-ethylanthrahydroquinone redox process. (From Xi, Z. et al., Science, 292, 1139, 2001.)...

Scheme 102 Catalytic cycle for the epoxidation of alkenes with iron or manganese complexes.

S.3 Cytochrome P450 Model Compounds Functional. Ferric-peroxo species are part of the cytochrome P450 catalytic cycle as discussed previously in Section 7.4.4. For instance, these ferric-peroxo moieties are known to act as nucleophiles attacking aldehydic carbon atoms in oxidative deformylations to produce aromatic species.An example of this work, establishing the nucleophilic nature of [(porphyrin)Fe (02)] complexes, was achieved for alkene epoxidation reactions by J. S. Valentine and co-workers. The electron-deficient compound menadione (see Figure 7.18) yielded menadione epoxide when reacted with a [(porphyrin)Fe X02)] complex. 

Scheme 2. Catalytic cycle for the electrochemical epoxidation of alkenes using silver(l)bis(2 -bipyridine).

Some typical epoxidations are listed in Table 3.1. The first Ru-catalysed epoxida-tion was reported in 1983 by James et al., in which RuBrlPPh XOEPl/PhlO/CHjClj was used to epoxidise styrene, norbomene and c/x-stilbene in low yields trans-stilbene was not oxidised [588]. It was later noted that tranx-RulOl lTMPl/Oj/C H aerobically oxidised cyclic alkenes, and a catalytic cycle involving Ru 0(TMP) was proposed, in which there is disproportionation of Ru(0)(TMP) to Ru(TMP) and fran -Ru(0)2(TMP), the latter epoxidising the alkene and the former being oxidised back to the latter by (Fig. 1.26) [46, 583]. Stilbene, tranx-styrene and norbomene were efficiently epoxidised by trani-RulOl lTMPl/lCl pyNOl/CgH [589], as was epoxidation of exo-norbomenes catalysed by trani-RulOl lTMPl/Oj/ CgHg [590]. 

Fig. 1.26 Catalytic cycle for aerobic alkene epoxidation by lrani-Ru(0),(TMP) [46, 583]...

Preparation of nonracemic epoxides has been extensively studied in recent years since these compounds represent useful building blocks in stereoselective synthesis, and the epoxide functionality constitutes the essential framework of various namrally occurring and biologically active compounds. The enantiomericaUy enriched a-fluorotropinone was anchored onto amorphous KG-60 silica (Figure 6.6) this supported chiral catalyst (KG-60-FT ) promoted the stereoselective epoxidation of several trans- and trisubstituted alkenes with ees up to 80% and was perfectly reusable with the same performance for at least three catalytic cycles. 

However, attempts to develop similar selective catalysts failed in the case of reactions that require one oxygen atom, like the oxidation of methane, ethane and other alkanes to alcohols, aromatic compounds to phenols, alkenes to epoxides, and many others. These mechanistically simple reactions assume one difficult condition the presence of active sites that upon obtaining two atoms from gas-phase 02 can transfer only one of them to the molecule to be oxidized, reserving the second atom for the next catalytic cycle with another molecule. This problem remains a hard challenge for chemical catalysis. 

Scheme 10.11 Mixed catalytic cycle for hydroperoxide formation in alkane oxygenation and alkene epoxidation with HOOH and cw-VO(bpy)2Y, via a homolytic and heterolytic cleavage of peroxo intermediates, respectively (after Knops-Gerrits et alPTi).

Although a large number of asymmetric catalytic reactions with impressive catalytic activities and enantioselectivities have been reported, the mechanistic details at a molecular level have been firmly established for only a few. Asymmetric isomerization, hydrogenation, epoxidation, and alkene dihydroxylation are some of the reactions where the proposed catalytic cycles could be backed with kinetic, spectroscopic, and other evidence. In all these systems kinetic factors are responsible for the observed enantioselectivities. In other words, the rate of formation of one of the enantiomers of the organic product is much faster than that of its mirror image. 

The Jacobsen-Katsuki-catalysts (Fig. 13) have recently received much attention as the most widely used alkene epoxidation catalysts. An example of Jacobsen s manganese-salen catalyst is shown in Fig. 13. They promote the stereoselective conversion of prochiral olefins to chiral epoxides with enantiomeric excesses regularly better than 90% and sometimes exceeding 98%.82,89,92,93,128 The oxidation state of the metal changes during the catalytic cycle as shown in Scheme 8. 

From Iron(III) Tetraarylporphyrins and Alkenes. N-alkyl porphyrins are formed via side reactions of the normal catalytic cycle of cytochromes P-450 with terminal alkenes or alkynes. N-alkylpor-phyrins formed from terminal alkenes (with model iron porphyrin catalysts under epoxidation conditions) usually have a covalent bond between the terminal carbon atom of the alkene and a pyrrole nitrogen. The double bond is oxidized selectively to an alcohol at the internal carbon. Mansuy (23) showed that, in isolated examples, terminal alkenes can form N-alkylated products in which the internal carbon is bound to the nitrogen and the terminal carbon is oxidized to the alcohol. Internal alkenes may also form N-alkyl porphyrins (24, 25). 

The catalytic asymmetric epoxidation of alkenes offers a powerful strategy for the synthesis of enantiomerically enriched epoxides and enantioselective oxidation reactions in ionic liquids have been summarised previously.[39] Complexes based on chiral salen ligands - usually with manganese(III) as the coordinated metal - often afford excellent yields and enantioselectivities and the catalytic cycle for the reaction is depicted in Scheme 5.5 J40 ... 

Mechanism of epoxidation The oxygen transfer occurs by a two-step catalytic cycle (Scheme 1.14). In the first step oxygen is transferred to the Mn(III) by an oxidant. The oxygen coordinates to the metal. In the second step the activated oxygen is delivered to the alkene. 

A polyoxometalate is also at the heart of an enantioselective epoxidation of allylic alcohols using a C-2 symmetric chiral hydroperoxide 39 derived from l,l,4,4-tetraphenyl-2,3-0-isopropylidene-D-threitol (TADDOL). Thus, in the presence of the oxovanadium(IV) sandwich-type POM [ZnW(V0)2(ZnW9034)2]12- and stoichiometric amounts of hydroperoxide 39, the dienol 40 is converted to the (2R) epoxide 41 in 89% yield and 83% ee. The proposed catalytic cycle invokes a vanadium(V) template derived from the POM, substrate, and hydroperoxide, a hypothesis supported by the lack of enantioselectivity with unfunctionalized alkenes. The catalytic turnover is remarkably high at about 40,000 TON <03OL725>. 

Two catalytic pathways for the alkene epoxidation may be described, corresponding to the concentration of the hydrogen peroxide used. If 85 % hydrogen peroxide is used, only 2 appears to be responsible for the epoxidation activity (Scheme 1, cycle I). 

A. M. Daly, M. F. Renehan, D. G. Gilheany, High enantioselectivities in an (E)-alkene epoxidation by catalytically active chromium salen complexes. Insight into the catalytic cycle, Org. Lett. 3 (2001) 663. 

FIGURE 19.1 Schematic diagram of the catalytic cycle involving a metal catalyst that transfers oxygen from an oxidant to an alkene to form an epoxide. 

There is also debate about the nature of the intermediates involved in the second step in the catalytic cycle illustrated in Fig. 19.1, that is, the transfer of oxygen to the alkene to form the epoxide. No intermediates have been detected experimentally, but five different possibilities have been proposed in the literature for the alkene complexed to the oxidized porphyrin [11,25-29]. The five proposed intermediates are radical, cation, concerted, metallaoxetane, and pi-radical-cation species. The literature is rather complicated due to the lack of direct experimental observation, and it is not clear that conclusions from, say, iron and chromium porphyrins also apply to manganese porphyrins [28]. Arasasingham et al. claim unequivocal evidence for a radical intermediate being involved in the oxidation of alkenes by manganese porphyrins [28]. They also discuss a charge-transfer complex that is similar to the concerted intermediate. Recently, density functional theory (DFT) and quantum mechanics/molecular mechanics (QM/MM) calculations were applied to styrene epoxidation by Mn-porphyrins ... 

This chapter describes computational strategies for investigating the species in the catalytic cycle of the enzyme cjdochrome P450, and the mechanisms of its main processes alkane hydroxylation, alkene epoxidation, arene hydroxylation, and sulfoxidation. The methods reviewed are molecular mechanical (MM)-based approaches (used e.g., to study substrate docking), quantum mechanical (QM) and QM/MM calculations (used to study electronic structure and mechanism). 

The first indication of selective substitution reactions came from experiments with 1 and 2 as catalysts for alkene epoxidation. NMR experiments have shown that both compounds catalyze the epoxidation of cyclohexene with t-butyl hydroperoxide (TBHP). The catalytic activity is comparable to that of the model compound Hex7Si70i2Ti(0 Pr). " The measured turn over numbers indicate that all four Ti centers are involved in the catalytic process. The catalysts could be recovered quantitatively, a proof of core-functionalization and for the core stability during many catalytic cycles. A more detailed catalytic study has recently been performed with the cubic titanasiloxane [(2,6- Pr2C6H3) (Me3Si)NSi]40i2[Ti0 Bu]4 (12). This compound was prepared by the reaction of 9 with t-butanol and catalyzes the epoxidation of cyclohexene with TBHP. The titanium butylperoxo intermediate could be isolated after a stoichiometric reaction with TBHP. This intermediate then reacted with cyclohexene to produce cyclohexene oxide. A schematic representation of the catalytic process is given in Figure 28.4. 

Figure 28.5. Catalytic cycle in the epoxidation of alkenes by cubic titanasilsesquioxanes (represented by (=SiO)3TiOR).

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