Stereoselective reactions epoxidation

Silyl ethers serve as preeursors of nucleophiles and liberate a nucleophilic alkoxide by desilylation with a chloride anion generated from CCI4 under the reaction conditions described before[124]. Rapid intramolecular stereoselective reaction of an alcohol with a vinyloxirane has been observed in dichloro-methane when an alkoxide is generated by desilylation of the silyl ether 340 with TBAF. The cis- and tru/u-pyranopyran systems 341 and 342 can be prepared selectively from the trans- and c/.y-epoxides 340, respectively. The reaction is applicable to the preparation of 1,2-diol systems[209]. The method is useful for the enantioselective synthesis of the AB ring fragment of gambier-toxin[210]. Similarly, tributyltin alkoxides as nucleophiles are used for the preparation of allyl alkyl ethers[211]. 

This chemical bond between the metal and the hydroxyl group of ahyl alcohol has an important effect on stereoselectivity. Asymmetric epoxidation is weU-known. The most stereoselective catalyst is Ti(OR) which is one of the early transition metal compounds and has no 0x0 group (28). Epoxidation of isopropylvinylcarbinol [4798-45-2] (1-isopropylaHyl alcohol) using a combined chiral catalyst of Ti(OR)4 and L-(+)-diethyl tartrate and (CH2)3COOH as the oxidant, stops at 50% conversion, and the erythro threo ratio of the product is 97 3. The reason for the reaction stopping at 50% conversion is that only one enantiomer can react and the unreacted enantiomer is recovered in optically pure form (28). 

If R and R are different, the two faces of the double bond become nonequivalent, permitting stereoselective reactions at the double bond. These effects have been explored, for example, using 4-silyl-2-pentenes. Reactions such as epoxidation and hydroboration proceed by preferential addition fiom the face opposite the bulky silyl substituents. 

R)-epoxide. It is noteworthy that this stereoselective reaction cannot be accomplished with transition-metal catalysts. 

In contrast to the metabolism of BA and BaP, the 5,6-dihydrodiols formed in the metabolism of DMBA by liver microsomes from untreated, phenobarbital-treated, and 3-methylcholanthrene-treated rats are found to have 5R,6R/5S,6S enantiomer ratios of 11 89, 6 94, and 5 95, respectively (7.49 and Table II). The enantiomeric contents of the dihydrodiols were determined by a CSP-HPLC method (7.43). The 5,6-epoxide formed in the metabolism of DMBA by liver microsomes from 3MC-treated rats was found to contain predominantly (>97%) the 5R,6S-enantiomer which is converted by microsomal epoxide hydrolase-catalyzed hydration predominantly (>95%) at the R-center (C-5 position, see Figure 3) to yield the 5S,6S-dihydrodiol (49). In the metabolism of 12-methyl-BA, the 5S,6S-dihydrodiol was also found to be the major enantiomer formed (50) and this stereoselective reaction is similar to the reactions catalyzed by rat liver microsomes prepared with different enzyme inducers (unpublished results). Labeling studies using molecular oxygen-18 indicate that 5R,68-epoxide is the precursor of the 5S,6S-dihydrodiol formed in the metabolism of 12-methyl-BA (51). 

In the application of the above discovery, ( )-3-benzyloxy-2-methyl pro-pionaldehyde 52 is used as the starting material in the synthesis of rifamycin A. As outlined in Scheme 7-12, compound 52 is converted to allyic alcohol 55 via a series of chemical reactions. Epoxidation of 55 proceeded stereoselectively, giving a single epoxide that affords 57 after subsequent treatment. Compound 57 may be converted to 58 upon acetonide formation. 

Terashima et al. 231) reported an asymmetric halolactonization reaction. This highly stereoselective reaction permits the synthesis of intermediates for the preparation of chiral a,a-disubstituted a-hydroxycarboxylic acids (227)231c), a-hydroxyketones (228) 231c), functionalized epoxides (229) 231d,e) and natural products 231h,j). Only amino acids have so far been used as a source of the chiral information in the asymmetric halolactonization reaction. Again, the best results have been obtained by using cyclic imino acid enantiomers, namely proline. 

Stereoselective reaction with ketones. The reaction of ketone 1 with methyl-lithium, trimethylaluminum, and lithium letramethylaluminate shows no stcrco-specificity. The reaction with mcthylmagncsium bromide gives the two possible adducts in the ratio 2.4 1. The best stereospccificity is observed with dimethylsulf-oxonium methylide, which converts 1 into 2 and 3 in a ratio about 5 1. Reduction of the epoxides with lithium triethylborohydride gives the desired tertiary alcohols. This reaction was used in a synthesis of ( ) stemodin (4).2... 

The epoxidation of cis- and trans-1-hydroxy-3,7-dimethylocta-2,6-diene with H202 and TS-1 is chemoselective at the 2-position and stereoselective no epoxidation takes place at the 6-position, and reactant molecules retain their structure in the products. The interesting results have been described as hydroxy-assisted epoxidation. The role of the OH group in the reaction is confirmed by the fact that in the epoxidation of cyclopent-2-en-l-ol, the product with the O cis to the OH group is favored over the one in trans by a factor of 9 1. The same steric preference was found in the epoxidation of cyclo-hex-2-en-l-ol (Kumar et al., 1995). 

The radical mechanism has also been proposed as a general mechanism for oxidation of alkenes and aromatics, but several objections have been raised because of the absence of products typically associated with radical reactions. In classical radical reactions, alkenes should react also at the allylic position and give rise to allyl-substituted products, not exclusively epoxides methyl-substituted aromatics should react at the benzylic position. The products expected from such reactions are absent. Another argument was made against the radical mechanism based on the stereoselectivity of epoxidation. Radical intermediates are free to rotate around the C C bond, with the consequence that both cis- and /rani-epoxides are formed from a single alkene isomer, contrary to the evidence obtained with titanium silicates (Clerici et al., 1993). 

Epoxidation. Oxone decomposes in the presence of a ketone (such as acetone) to form a species, possibly a dioxirane (a), which can epoxidize alkenes in high yield in reactions generally conducted in CH2C12-H20 with a phase-transfer catalyst. An added ketone is not necessary for efficient epoxidation of an unsaturated ketone. The method is particularly useful for preparation of epoxides that are unstable to heat or acids and bases.3 The acetone-Oxone system is comparable to m-chloroperbenzoic acid in the stereoselectivity of epoxidation of allylic alcohols. It is also similar to the peracid in preferential attack of the double bond in geraniol (dienol) that is further removed from the hydroxyl group.4... 

As noted earlier, one reason for the powerful nature of the Sharpless epoxidation is the ability of the resultant epoxy alcohols to undergo regioselective and stereoselective reaction with nucleo-philes.4 18 20 5155 Often the regiochemistry is determined by the functional group within the substrate.51483... 

The as-decalin is formed because the enone, though flattened, is already folded to some extent. A conformational drawing of either molecule shows that the top surface is better able to bind to the flat surface of the. catalyst. Each of these products shows interesting stereoselective reactions. The ketal can be converted into an alkene by Grignard addition and El elimination and then epoxidized. Everything happens from the outside as expected with the result that the methyl group is forced inside at the epoxidation stage. 

The confomiational preferences and stereoselective reactions of a number of macrocyclic systems have been studied. The stereochemical results have been explained on the basis of the model of local conformer control. The epoxidation of a macrocyclic alkene containing the substitution pattern (21) provides a single epoxide having the stereochemistry (22). A macrocycle containing a l,S-diene system adepts the local confoimation (23) that is iree of torsional strain epoxidation of (23) from the less hindered side fiimishes the syn-diepoxide (24). The MCPBA epoxidations of the unsaturated macrocyclic lactones (25) and (2Q are stereoselective (equations 9 and 10). In the epoxidation of (26) six new chiral centres are introduced the reaction product is a 20 1 1 mixture of triepoxides. The tiiepoxide (27) is closely related to the C(9)-C(23) segment of monensin B. 

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