Asymmetric epoxidation solvent

The asymmetric epoxidation of enones with polyleucine as catalyst is called the Julia-Colonna epoxidation [27]. Although the reaction was originally performed in a triphasic solvent system [27], phase-transfer catalysis [28] or nonaqueous conditions [29] were found to increase the reaction rates considerably. The reaction can be applied to dienones, thus affording vinylepoxides with high regio- and enantio-selectivity (Scheme 9.7a) [29]. 

The insoluble polymer-supported Rh complexes were the first immobilized chiral catalysts.174,175 In most cases, however, the immobilization of chiral complexes caused severe reduction of the catalytic activity. Only a few investigations of possible causes have been made. The pore size of the insoluble support and the solvent may play important roles. Polymer-bound chiral Mn(III)Salen complexes were also used for asymmetric epoxidation of unfunctionalized olefins.176,177... 

Scheme 4-21 shows the preparation of L-threitol and L-erythritol.38 Epoxy alcohols (2J ,3iS)-61 and (2S,3/ )-61. generated by asymmetric epoxidation, are exposed to sodium benzenethiolate and sodium hydroxide in a protonic solvent to undergo base-catalyzed rearrangement, yielding the threo-diol 62 and erythro-diol 63, which can then be converted to the corresponding tetraacetate of l-threitol 67 and L-erythritol 69 through subsequent transformations. 

After the "asymmetric epoxidation" of allylic alcohols at the very beginning of the 80 s, at the end of the same decade (1988) Sharpless again surprised the chemical community with a new procedure for the "asymmetric dihydroxylation" of alkenes [30]. The procedure involves the dihydroxylation of simple alkenes with N-methylmorpholine A -oxide and catalytic amounts of osmium tetroxide in acetone-water as solvent at 0 to 4 °C, in the presence of either dihydroquinine or dihydroquinidine p-chlorobenzoate (DHQ-pClBz or DHQD-pClBz) as the chiral ligands (Scheme 10.3). 

The mechanism behind the polyamino acid-catalysed asymmetric epoxidation is particularly difficult to understand. The active catalyst exists as a paste or a gel following treatment with the organic solvent. Thus, studies on the helix/)8-sheet structure of the amorphous solid, the form of the polyamino acid in the absence of solvent, are probably not meaningful in this context. 

Efficient kinetic resolution of chiral unsaturated secondary alcohols by irreversible enzyme-mediated acylation (with vinyl acetate as acylating agent, a crude preparation of Pseudomonas AK, and hexane as solvent) is possible, provided one relatively large and one small substituent are attached to the carbinol carbon. However, the method can be used to resolve substrates that are not amenable to asymmetric epoxidation (see examples 23, 25, 27, 29, where the double bond is either deactivated by an electron-withdrawing substituent, or is of the propargyl alcohol type). Acylation of the / -enantiomer consistently proceeds faster than that of the 5-enantiomer. An example of an allenic alcohol was also reported248. 

Scheme 5.2-12 Mn-catalyzed asymmetric epoxidation in a [BMIM][PF6]/CH2Cl2 (v/v = 1 /4) solvent mixture.

The asymmetric epoxidation of several chalcones (39) and other electron-poor olefins in a triphase system (water/organjc solvent/chiral polyamino acid) afford optically active oxirans with optical yields of up to 96%. The influence of the molecular structure of the catalysts and substrates, the solvent, and the temperature on the stereochemistry was investigated by a group of chemists from Italy and Spain 77). 

For the asymmetric epoxidation reaction, dry alcohol-free dichloromethane (the use of dichloromethane stabilized with methanol must be avoided) is usually the solvent of choice It is inert to the reagents, has good solvent power for the components of the reaction, and supports good epoxidation rates. A fortunate consequence of the asymmetric epoxidation process is that ligation of the allylic alcohol to the Ti center aids in solubilization of the substrate. Substrates that normally may be only modestly soluble in the above-mentioned solvents will be brought into solution as they complex with the Ti-tartrate catalyst. 

Acetonitrile is the solvent of choice for in-situ C-H oxidation. Although ethereal solvents, for example dimethoxymethane, 1,2-dimethoxyethane, 1,4-dioxane, and mixtures thereof, have been successfully used for dioxirane-mediated catalytic asymmetric epoxidations, their application in in-situ C-H oxidation has not been vigorously established. 

Chiral asymmetric epoxidations have been intensively investigated due to the fundamental importance of epoxides in organic chemistry [69, 70], Nevertheless, catalytic asymmetric Lewis acid epoxidation of a,/i-unsaturated aldehydes remains a challenge to chemists. Recently, Jorgensen and co-workers developed the first asymmetric approach to epoxides of enals, in which chiral pyrrolidine 11 was used as catalyst and H2O2 as oxidant, thus following the concept of iminium catalysis (Scheme 3.9) [71-73]. Importantly, reaction conditions are tolerant to a variety of functionalities and this chemical transformation proceeds in different solvents, with no loss of enantioselectivity. (For experimental details see Chapter 14.13.1). 

As a solvent for the asymmetric epoxidation of 2,2-dimethylchromene mediated by Jacobsen s chiral (salen)-manganese catalyst.49... 

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).

C4Ciim][PF6] Mn(salen) complex NaOCl Asymmetric epoxidation CH2C12 as co-solvent reaction proceeds faster in the ionic liquid relative to conventional solvents product extracted with hexane catalyst was recycled 4 times, activity and selectivity slowly decrease. [48]... 

The original report32 of the titanium-catalyzed asymmetric epoxidation of allylic alcohols in 1980 has been followed by hundreds of applications, the majority of which use the initially reported conditions. In the decade since the introduction of this reaction numerous improvements have been made41. The most complete discussion of the preparative aspects of both the asymmetric epoxidation and the kinetic resolution was presented by the Sharpless group42. This paper details the effects of reagent stoichiometry and concentration, substrate concentration, aging of the catalyst and variation of oxidant, solvent and tartrate as well as workup procedures. What is particularly noteworthy in this presentation is that significant amounts of unpublished work are drawn upon to develop recommendations for successful reaction. 

Most Sharpless asymmetric epoxidations have been conducted in dichloromethane since this solvent was that initially employed. Other solvents that have been successfully used are toluene, heptane and isooctane. Due to the stability in storage of terf-butyl hydroperoxide in isooctane this solvent is now recommended, with dichloromethane and toluene as the next choices42. 

Aqua(phosphine)ruthenium(II) complexes [121] are useful for activation of molecular oxygen, and catalytic oxidation of cyclohexene can be carried out with 1 atm of O2 [121a,bj. The ruthenium catalyst bearing perfluorinated 1,3-diketone ligands catalyzes the aerobic epoxidation of alkenes in a perfluorinated solvent in the presence of i-PrCHO [122]. Asymmetric epoxidations of styrene and stilbene proceed with 56-80% e.e. with ruthenium complexes 38-40 (Figure 3.2) and oxidants such as PhI(OAc)2, PhIO, 2,6-dichloropyridine N-oxide, and molecular oxygen [123-125]. 

Quaternary ammonium salts of alkaloids have been used for the synthesis of optically active oxiranes from electron-poor olefins under phase-transfer conditions. The enantiomer yield is inversely proportional to the dielectric constant of the solvent,Asymmetric epoxidation in the presence of catalytic amounts of poly-(S)-amino-acids in a triphase system has been described with optical yields up to 96% ... 

The optimum conditions for the asymmetric epoxidation reaction were developed. Because of the exothermic nature of the reaction, a solution of TPPP in the reaction medium is cooled to the desired temperature the catalysts and substrate are also separately dissolved in the reaction solvent and cooled to the desired temperature. The solution of catalyst is added dropwise to the solution of oxidant, to minimize the increase in reaction temperature, which is allowed to stabilize before dropwise addition of the substrate. The alkene is added last to help maintain the epoxidation process at a constant temperature. The reaction is stopped by high dilution with diethyl ether, in which both the catalyst and oxidant display a low solubility profile. 

TABLE 5.12 Asymmetric epoxidation of 1-Phenylcyclohexene using various solvents"... 

The presence of a functional group in the vicinity of the epoxide can lead to interesting results. Such is the case for the epoxy-2,3 alcohols 2.23, which can be obtained in a nonracemic form by asymmetric epoxidation of the corresponding allylic alcohols [KS3]. The action of LAH in THF or better yet of Red-Al in the same solvent [MM2, VI] or preferably in DME [GS4] selectively leads to the 1,3-diols 2.24, while DIBAH [FKl] or LiBH4-(i-PrO)4Ti in [DLl] gives access to the 1,2-diols 2.25 (Figure 2.15). The hydride attack is stereospecific, and in the nonracemic chiral molecule 2.26, the reaction proceeds with inversion [FKl] (Figure 2.15). If the alcohol residue is transformed into a methyl ether, Red-Al does not promote any reduction [FKl]. 

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