Asymmetric epoxidation catalytic cycle

Figure 6A.7. Ligand exchange on titanium during the asymmetric epoxidation catalytic cycle.

The first attempt at a catalytic asymmetric sulfur ylide epoxidation was by Fur-ukawa s group [5]. The catalytic cycle was formed by initial alkylation of a sulfide (14), followed by deprotonation of the sulfonium salt 15 to form an ylide 16 and... 

Promising examples of the catalytic asymmetric Darzens condensation, which yields an epoxide product via carbon-carbon and carbon-oxygen bond formation, have been reported recently by two groups (Scheme 10.11). Toke and co-workers used crown ether 24 in the reaction to form the a,P-unsaturated ketone 78 [38b] with 64% ee, whereas the Shioiri group used the cinchona-derived salt 3a [52], which resulted in 78 with 69% ee. The latter authors propose a catalytic cycle involving generation of a chiral enolate in situ from an achiral inorganic base... 

Aggarwal et al. have proposed a catalytic cycle for asymmetric epoxidation of olefins by chiral amines (Scheme 7.13), which involves the initial formation of ammonium... 

As shown in cycle (b) in Scheme 10.1, the iminium-oxaziridinium pair can also effect catalytic asymmetric epoxidation of alkenes. Early work in this field by Bohe et al. included investigation of the norephedrine-derived oxaziridinium salt 34 (33% ee in the catalytic epoxidation of traws-stilbene [41] ee up to 61% was achieved when 34 was employed stoichiometrically [42]), or the L-proline-derived material 35 (39% ee in the epoxidation of trans-3-phenyl-2-propenol [43]). Rapid... 

The first asymmetric aziridination process to use catalytic amounts of ylide was reported by Aggarwal et al. in 1996 [77]. The proposed catalytic cycle (see Scheme 10.15) is analogous to that used in their asymmetric epoxidation process (see Sec-... 

As in catalytic ylide epoxidation (see Section 10.2.1.1), an alternative catalytic cycle can be based on generation of the ylide in situ by reaction of a sulfide with an alkyl halide to form a salt, which can then be deprotonated [76]. In 2001, Saito et al. reported the asymmetric version of this cycle using a 3 1 ratio of alkyl halide to sulfonyl imine (see Scheme 10.18) [81]. Good yields and ee-values were reported for aryl- and styryl-substituted aziridines using stoichiometric amounts of sulfide 24, and the diastereoselectivities ranged from 1 1 to 4 1. Unfortunately, when loadings were reduced the reaction times became longer and lower yields were reported (see Table 10.2). 

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. 

Figure 9.7 Catalytic cycle for asymmetric epoxidation of allyl alcohol with 9.35 as the precatalyst. The precatalyst is generated in situ and undergoes conversion to 9.36 in the presence of allyl alcohol and r-butyl hydroperoxide. S is a solvent molecule. Conversion of 9.36 to 9.37 involves more than one step. This is not shown for clarity (see Problem 10).

Chiral epoxides are important intermediates in organic synthesis. A benchmark classic in the area of asymmetric catalytic oxidation is the Sharpless epoxidation of allylic alcohols in which a complex of titanium and tartrate salt is the active catalyst [273]. Its success is due to its ease of execution and the ready availability of reagents. A wide variety of primary allylic alcohols are epoxidized in >90% optical yield and 70-90% chemical yield using tert-butyl hydroperoxide as the oxygen donor and titanium-isopropoxide-diethyltartrate (DET) as the catalyst (Fig. 4.97). In order for this reaction to be catalytic, the exclusion of water is absolutely essential. This is achieved by adding 3 A or 4 A molecular sieves. The catalytic cycle is identical to that for titanium epoxidations discussed above (see Fig. 4.20) and the actual catalytic species is believed to be a 2 2 titanium(IV) tartrate dimer (see Fig. 4.98). The key step is the preferential transfer of oxygen from a coordinated alkylperoxo moiety to one enantioface of a coordinated allylic alcohol. For further information the reader is referred to the many reviews that have been written on this reaction [274, 275]. 

Fig. 4.98 The catalytic cycle of the Sharpless catalytic asymmetric epoxidation.

Fig. 4.104 Catalytic cycle of asymmetric epoxidation via chiral dioxiranes.

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 ... 

Zanardi, J., Leriverend, C., Aubert, D., Julienne, K., Metzner, P. A catalytic cycle for the asymmetric synthesis of epoxides using sulfur ylides. J. Org. Chem. 2001, 66, 5620-5623. 

Bryliakov KP, Talsi EP (2003) Cr° (salen)Cl catalyzed asymmetric epoxidations insight into the catalytic cycle. Inorg Chem 42 7258-7265... 

The postulated catalytic cycle of the asymmetric epoxidation reaction is shown in Figure 13.10. A lanthanide metal alkoxide moiety changes to a rare earth metal-peroxide through proton exchange (I). In this step, lanthanide metal alkoxide moiety functions as a Bronsted base. The rare earth metal-BINOL complex also functions as a Lewis acid to activate electron-deficient olefins through monoden-tate coordination (II). Enantioselective 1,4-addition of rare earth metal-peroxide gives intermediate enolate (III), followed by epoxide formation to regenerate the catalyst (IV). 

Asymmetric epoxidation of terminal alkenes with hydrogen peroxide was optimized with electron-poor chiral Pt(II) complexes bearing a pentafluorophenyl residue, as described in Section 23.3.1.6. The same catal3rtic system was made more sustainable by the employment of water as the solvent under micellar conditions. Surfactant optimization revealed the preferential use of neutral species like Triton-XIOO to solubihze both the catalyst and substrates. In several cases an increase of the asymmetric induction was observed (Scheme 23.43). The use of an aqueous phase and the strong affinity of the catalyst for the micelle allowed the recycling of the catalytic system by means of phase separation and extraction of the reaction products using an apolar solvent (hexane). The aqueous phase containing the catalyst was reused for up to three cycles with no loss of activity or selectivity. 

After Kobayashi spioneering study on theabiUty of (S)-2,2 -bis(diphenylphosphanyl)-1,1 -binaphthyl dioxide (9, BINAPO) as a promoter of the enantioselective allylation of a-hydrazono esters with allyltrichlorosilanes [27], Nakajima reported the first catalytic system for the allylation of aldehydes, in which the use of N,N-diisopropylethylamine and tetrabutylammonium iodide was essential for accelerating the catalytic cycle (Scheme 7.16) [28], For this allylation, y-functionahzed nucleophiles such as cis-y-bromoallyltrichlorosilane could be employed as addressed by Maikov and Kodovsky [29], In addition, 9 could be apphed to the asymmetric ring opening of meso-epoxides with SiCh, as expected from the scope of the chiral bipyridine N,N -dioxide catalysis [30], and could also catalyze the SiCfi-mediated, enanhoselective phosphonylation of aldehydes with trialkyl phosphites [31],... 

Scheme 19.13 Proposed catalytic cycle for asymmetric epoxidation using catalyst 34.

Despite the tremendous success of hydroxyl-directed asymmetric epoxidation of allylic alcohols and homoallylic alcohols, the development of efficient asymmetric epoxidation methods for unfunctionalized olefins is still of great importance. In the mid-1980s, Kochi and co-workers studied achiral epoxidation of unfunctionalized olefins using achiral Cr(III)-salen and Mn(lll)-salen comlexes as catalysts, and they proposed that a high valent metal oxo (such as 0=Cr(V)-salen and 0=Mn(V)-salen species) as the reactive intermediate was responsible for the epoxidation of olefins. Such a reactive intermediate was formed in a catalytic cycle by oxidation of the catalyst (such as Cr(III)-salen or Mn(lll)-salen complex) with the stoichiometric oxidant (such as PhlO or NaOCl). ... 

Discovering highly enantioselective ketone catalysts for asymmetric epoxidation has proven to be a challenging process. As shown in Scheme 3.62, quite a few processes are competing with the catalytic cycle of the ketone mediated epoxidation, including racemization of chiral control elements, excessive hydration of the carbonyl, facile... 

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