Epoxidation, enantioselective mechanism

The first reports of a reaction of an amine with an aldehyde by Schiff [584] led to the establishment of a large class of ligands called Schiff bases. Among the most important of the Schiff bases are the tetradentate salen ligands (N,N -bis(salicy-laldehydo)ethylenediamine), which were studied extensively by Kochi and coworkers, who observed their high potential in chemoselective catalytic epoxidation reactions [585]. The best known method to epoxidize unfunctionalized olefins enantioselectively is the Jacobsen-Katsuki epoxidation reported independently by these researchers in 1990 [220,221]. In this method [515,586-589], optically active Mn salen) compounds are used as catalysts, with usually PhlO or NaOCl as the terminal oxygen sources, and with a O=Mn (salen) species as the active [590,591] oxidant [586-594]. Despite the undisputed synthetic value of this method, the mechanism by which the reaction occurs is still the subject of considerable research [514,586,591]. The subject has been covered in a recent extensive review [595], which also discusses the less-studied Cr (salen) complexes, which can display different, and thus useful selectivity [596]. Computational and H NMR studies have related observed epoxide enantioselectivities... 

Jacobsen developed a method employing (pybox)YbCl3 for TMSCN addition to meso-epoxides (Scheme 7.22) [46] with enantioselectivities as high as 92%. Unfortunately, the practical utility of this method is limited because low temperatures must be maintained for very long reaction times (up to seven days). This reaction displayed a second-order dependence on catalyst concentration and a positive nonlinear effect, suggesting a cooperative bimetallic mechanism analogous to that proposed for (salen)Cr-catalyzed ARO reactions (Scheme 7.5). 

Nakajima reported the use of a chiral bipyridine N,N -dioxide 18 in the desym-metrization of acyclic meso epoxides (Figure 7.3). Although the enantioselectivity was not as high as in the method developed by Fu for meso-stilbene oxide (90% ee vs. 94% ee), it was higher for the same aliphatic epoxide (74% ee vs. 50% ee) [57]. Nakajima showed that mono-N-oxide derivatives 19 and 20 were much less effective than 18 in tenns of both yield and enantioselectivity, and accordingly proposed a unique mechanism for 18 involving a hexacoordinate silicon intermediate coordinated to both N-oxides of the catalyst. 

Allylic alcohols can be converted to epoxy-alcohols with tert-butylhydroperoxide on molecular sieves, or with peroxy acids. Epoxidation of allylic alcohols can also be done with high enantioselectivity. In the Sharpless asymmetric epoxidation,allylic alcohols are converted to optically active epoxides in better than 90% ee, by treatment with r-BuOOH, titanium tetraisopropoxide and optically active diethyl tartrate. The Ti(OCHMe2)4 and diethyl tartrate can be present in catalytic amounts (15-lOmol %) if molecular sieves are present. Polymer-supported catalysts have also been reported. Since both (-t-) and ( —) diethyl tartrate are readily available, and the reaction is stereospecific, either enantiomer of the product can be prepared. The method has been successful for a wide range of primary allylic alcohols, where the double bond is mono-, di-, tri-, and tetrasubstituted. This procedure, in which an optically active catalyst is used to induce asymmetry, has proved to be one of the most important methods of asymmetric synthesis, and has been used to prepare a large number of optically active natural products and other compounds. The mechanism of the Sharpless epoxidation is believed to involve attack on the substrate by a compound formed from the titanium alkoxide and the diethyl tartrate to produce a complex that also contains the substrate and the r-BuOOH. ... 

E. J. Corey, F.-Y. Zhang, Mechanism and Conditions for Highly Enantioselective Epoxidation of a,p-Enones Using Charge-Accelerated Catalysis by a Rigid Quaternary Ammonium Salt , Org. Lett. 1999,1,1287-1290. 

The same Pt species that epoxidize double bonds are active in Baeyer-ViUiger oxidation of ketones. Strukul has shown that this synthetically interesting process can be carried out also enantioselectively, in the presence of appropriate diphosphine ligands For this reaction a mechanism has been proposed that involves again a quasi-peroxo metallacycle intermediate, even though in this reaction the metal catalyst plays primarily the role of a Lewis acid while the real oxidant is H2O2 itself (Scheme 9). 

In 1980, Katsuki and Sharpless described the first really efficient asymmetric epoxidation of allylic alcohols with very high enantioselectivities (ee 90-95%), employing a combination of Ti(OPr-/)4-diethyl tartrate (DET) as chiral catalyst and TBHP as oxidant Stoichiometric conditions were originally described for this system, however the addition of molecular sieves (which trap water traces) to the reaction allows the epoxidation to proceed under catalytic conditions. The stereochemical course of the reaction may be predicted by the empirical rule shown in equations 40 and 41. With (—)-DET, the oxidant approaches the allylic alcohol from the top side of the plane, whereas the bottom side is open for the (-l-)-DET based reagent, giving rise to the opposite optically active epoxide. Various aspects of this reaction including the mechanism, theoretical investigations and synthetic applications of the epoxy alcohol products have been reviewed and details may be found in the specific literature . 

Goncalves et have compared the amine (V) and the iminium salt (W) for the enantioselective epoxidation of some prochiral olefins in acetonitrile/water and found that the yields and ees are nearly the same for the epoxidation of a selection of olefins. The amines of type (X) are less well developed. Armstrong has summarized the developments in this field and suggested mechanisms based on hydrogen bonded species, one of which is shown in Figure 1.49. Typical yield and ee data for the epoxidation of 1-phenylcyclohexene for these catalysts are also shown in Figure 1.49. 

Jonsson, S., Odille Fabrice, G.J., Norrby, P.-O. and Warnmark, K. (2006) Modulation of the reactivity, stability and substrate- and enantioselectivity of an epoxidation catalyst by noncovalent dynamic attachment of a receptor functionality - aspects on the mechanism of the Jacobsen-Katsuki epoxidation applied to a supramolecular system. Org. Biomol. Chem., 4, 1927-1948 Jonsson, S., Odille Fabrice, G.J., Norrby, P.-O. and Warnmark, K. (2005) A dynamic supramolecular system exhibiting substrate selectivity in the catalytic epoxidation of olefins. Chem. Commun., 549-551. 

An alternate mechanism invoking an ion-pair transition-state assembly has been proposed to account for the enantioselectivity of the asymmetric epoxidation process [137]. In this proposal, two additional alcohol species are required in the transition-state complex. This... 

Collman et al. have recendy reported that threitol-strapped manganese(IH)-porphyrin complex 7 shows high enantioselectivity in the epoxidation of a wide range of olefins when the reaction is carried out in the presence of 1,5-dicyclohexylimidazole (Scheme 6B. 12) [22], The substituted imidazole in this reaction appears to play the same role as the imidazole in Inoue s reaction. Detailed understanding of the mechanism of asymmetric induction by 7 needs further investigation, the major pathway should accommodate the steric interaction between the olefinic substituent and the inner oxygen atom of the threitol strap (Figure 6B.6). Thus, the pathway a is likely to be the major pathway,... 

Preparation of optically active P-ionone epoxide by a solid state kinetic resolution in the presence of the chiral host 10a is also possible. When a mixture of 10a, P-ionone (66) and m-chloroperbenzoic acid (MCPBA) is ground by mortar and pestle in the solid state, (+)-67 of 88% ee was obtained.29 Mechanism of the kinetic resolution is shown below. Of course, all processes proceed in the solid state. Firstly, oxidation of 66 with MCPBA gives rac-P-ionone epoxide (67). Secondly, enantioselective inclusion of (+)-67 with 10a occurs. Thirdly, uncomplexed (-)-67 is oxidized to give the Baeyer- Villiger oxidation product (-)-68 of 72% ee. This is the first example of the resolution by an enantioselective inclusion complexation in the solid state. 

An aggravating phenomenon associated with the (salen)Mn complexes is that the epoxidation of /ram-olefins proceeds typically with low ee s. Remarkably, however, the analogous chromium complexes (e.g., 14) catalyze such epoxidations with greater selectivity than for the corresponding d.v-olefins under the same conditions. Here the mechanism is presumed to involve an electrophilic process, which is supported by the fact that only electron-rich alkenes are effectively epoxidized. In the case of ram-l.l-methy 1-styrcnc (15), enantioselectivities of ca. 80% are observed [95TL7739],... 

Stoichiometric sulfur ylide epoxidation was first reported by A.W. Johnson [23] in 1958, and subsequently the method of Corey and Chaykovsky has found widespread use [24-26]. The first enantioselective epoxidations using stoichiometric amounts of ylide were reported in 1968 [27, 28]. In another early example, Hiyama et al. used a chiral phase-transfer catalyst (20 mol%) and stoichiometric amounts of Corey s ylide to effect asymmetric epoxidation of benzaldehyde in moderate to good enantiomeric excess (ee) of 67 to 89% [29]. Here, we will focus on epoxidations using catalytic amounts of ylide [30-32]. A general mechanism for sulfur ylide epoxidation is shown in Scheme 10.2, whereby an attack by the ylide on a carbonyl group yields a betaine intermediate which collapses to yield... 

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