Asymmetric epoxidation substrate structure

Besides ruthenium porphyrins (vide supra), several other ruthenium complexes were used as catalysts for asymmetric epoxidation and showed unique features 114,115 though enantioselectivity is moderate, some reactions are stereospecific and treats-olefins are better substrates for the epoxidation than are m-olcfins (Scheme 20).115 Epoxidation of conjugated olefins with the Ru (salen) (37) as catalyst was also found to proceed stereospecifically, with high enantioselectivity under photo-irradiation, irrespective of the olefmic substitution pattern (Scheme 21).116-118 Complex (37) itself is coordinatively saturated and catalytically inactive, but photo-irradiation promotes the dissociation of the apical nitrosyl ligand and makes the complex catalytically active. The wide scope of this epoxidation has been attributed to the unique structure of (37). Its salen ligand adopts a deeply folded and distorted conformation that allows the approach of an olefin of any substitution pattern to the intermediary oxo-Ru species.118 2,6-Dichloropyridine IV-oxide (DCPO) and tetramethylpyrazine /V. V -dioxide68 (TMPO) are oxidants of choice for this epoxidation. 

D. C. Zeldin, S. Wei, J. R. Falck, B. D. Hammock, J. P. Snapper, J. H. Capdevilla, Metabolism of Epoxyeicosatrienoic Acids by Cytosolic Epoxide Hydrolase Substrate Structural Determinants of Asymmetric Catalysis , Arch. Biochem. Biophys. 1995, 316, 443 - 451. 

The effect of structural variation and the use of different caboxylate salts as cocatalysts was investigated by Pietikainen . The epoxidation reactions were performed with the chiral Mn(III)-salen complexes 173 depicted in Scheme 93 using H2O2 or urea hydrogen peroxide as oxidants and unfunctionalized alkenes as substrates. With several soluble carboxylate salts as additives, like ammonium acetate, ammonium formate, sodium acetate and sodium benzoate, good yields (62-73%) and moderate enantioselectivities (ee 61-69%) were obtained in the asymmetric epoxidation of 1,2-dihydronaphthalene. The results were better than with Ai-heterocycles like Ai-methylimidazole, ferf-butylpyridine. 

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). 

Allylic alcohols with a cis-3-substituent (45) are the slowest to be epoxidized, and they give the most variable enantiofacial selectivity. Both these characteristics suggest that allylic alcohols of this structure have the poorest fit to the requirements of the active epoxidation catalyst. Nevertheless, asymmetric epoxidation of these substrates is still effective and in most cases gives an enantiomeric purity of at least 80% ee and often as high as 95% ee. Patience with the slower reaction rate usually is rewarded with chemical yields of epoxy alcohols comparable with those obtained with other allylic alcohols. A number of representative examples are collected in Table 6A.5 [2,4,38,59,62a,71-78],... 

A limited number of allylic alcohols of the (2,3Z)-disubstituted type have been subjected to asymmetric epoxidation. With one exception, the C-2 substituent in these substrates has been a methyl group, the exception being a f-butyl group [38]. The (3Z)-substituents have been more varied, as illustrated by structures 61-64, which show the epoxy alcohols derived from the corresponding allylic alcohol substrates. 

Asymmetric epoxidation of allylic alcohols is a very reliable chemical reaction. More than a decade of experience has confirmed that the Ti-tartrate catalyst is extremely tolerantof structural diversity in the allylic alcohol substrate for epoxidation yet is highly selective in its ability to discriminate between the enantiofaces of the prochiral olefin. Today the practitioner of organic chemistry need provide only the allylic alcohol to perform the reaction. All other reagents and materials required for the reaction are available from supply houses and usually are sufficiently pure as received to be used directly in the asymmetric epoxidation process. [When purchasing f-butyl hydroperoxide in prepared solutions, however, the more concentrated 5.5-M solution in isooctane (2,2,4-trimethylpentane) should always be chosen over the 3.0-M solution.] If the considerations presented in this chapter are observed, with attention to the moderately stringent technique outlined, no difficulty should be encountered in performing this reaction. 

A remaining goal related to asymmetric epoxidation is to obtain additional structural information about the Ti-tartrate catalyst as well as about the catalyst loaded with substrate and oxidant. 

The allylic alcohol binds to the remaining axial coordination site where stereochemical and stereoelec-tronic effects dictate the conformation shown in Figure 5. The structural model of catalyst, oxidant and substrate shown in Figure 5 illustrates a detailed version of the formalized rule presented in Figure 1. Ideally, all the observed stereochemistry of epoxy alcohol and kinetic resolution products can be rationalized according to the conq>atibility of their binding with the stereochemistry and stereoelectronic requirements imposed by this site. A transition state model for the asymmetric epoxidation complex has been calculated by a frontier orbital preach and is consistent with the formulation portrayed in Figure... 

Substrate structure has a dramatic influence on the rate of the Sharpless asymmetric epoxidation. -Disubstituted and trisubstituted allylic alcohols react the most rapidly whereas Z-disubstituted and unsyininetrical disubstituted analogs react much more slowly32. Chemical yields for these substitution patterns are all in the range of 77-87% and enantioselection is in the range of 95% ee except for the slow-reacting Z-disubstituted allylic alcohols that exhibit enantioselectivities in the range of 90 % ee. 

A range of structurally different chiral primary amines was converted into the corresponding iminium tetraphenylborate salts (Fig. 5.3) and tested in the asymmetric epoxidation of a standard test substrate, 1-phenylcyclohexene, using Oxone (4 equiv) as the stoichiometric oxidant, sodium carbonate (8 equiv) as base, in acetonitrile/water (2 1) at 0 °C (Table 5.1) [19,21]. 

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