Alcohols, 2,3-epoxy stereochemistry

The corresponding syn-compound can also be synthesized by simply inverting the stereochemistry of the hydroxyl group of the epoxy alcohol by the Mitsunobu reaction [54], Therefore, this method provides a simple and reliable method for the synthesis of any enantiomers and diastereomers of straight-chain 1,2-polyols. 

Reaction with aldehydes gives trifluoromethylated epoxy alcohols with good diastere-oselectivities (around 80 20) however, the relative stereochemistry of the products is not reported. 

Contrary to the case of anionic reactions, the formation of a strong proton-bound dimer for alcohols suggests that nucleophilic displacement may actually involve a frontside attack. Recent experiments carried out at atmospheric pressure by Speranza and Angelini (1980) using radiolytic techniques with isolation and glc analysis of neutral products reveal some interesting stereochemistry. For example, the reaction of protonated epoxy-rra/is-but-2-ene with H20 results in 98% inversion of configuration, while a similar reaction with cis-1 -chloro-4-methylcyclohexane results in approximately 80% of tro/is-4-methylcyclohexanol. With the high pressures utilized and with the possible participation of cluster ions a likelihood in this case, the data are consistent with a Walden inversion for these cases. 

Compatibility of asymmetric epoxidation with acetals, ketals, ethers, and esters has led to extensive use of allylic alcohols containing these groups in the synthesis of polyoxygenated natural products. One such synthetic approach is illustrated by the asymmetric epoxidation of 15, an allylic alcohol derived from (S)-glyceraldehyde acetonide [59,62]. In the epoxy alcohol (16) obtained from 15, each carbon of the five-carbon chain is oxygenated, and all stereochemistry has been controlled. The structural relationship of 16 to the pentoses is evident, and methods leading to these carbohydrates have been described [59,62a]. 

The two methods are complementary in terms of stereochemistry, such that if a 2,3-epoxy alcohol of the same absolute configuration is used to start each sequence, the erythm-1,2-ep-oxy-3-ols produced will have opposite configurations at C-2 and C-3. This result is because inversion occurs at C-2 during the Payne rearrangement, whereas in the epoxy-mesylate opening, inversion occurs at C-3. Detailed discussions of these Payne rearrangement processes as well as of further synthetic transformations of the 1,2-epoxy alcohols have been presented elsewhere [11,65]. 

The allylic alcohol binds to the remaining axial coordination site, where stereochemical and stcrcoelectronic effects dictate the conformation shown in Figure 6A.9 [6]. The structural model of catalyst, oxidant, and substrate shown in Figure 6A.9 illustrates a detailed version of the formalized rule presented in Figure 6A. 1. Ideally, all observed stereochemistry of epoxy alcohol and kinetic resolution products can be rationalized according to the compatibility of their binding with the stereochemistry and stereoelectronic requirements imposed by this site [6]. A... 

Scheme 8.11 Payne-like opening of epichloro-hydrin during syntheses of aryloxypropanola-mine beta-blockers. Pathway A shows a true Payne rearrangement [178] as it pertains to how a 2,3-epoxy alcohol becomes isomerized when treated with aqueous base. Step 1 is meant to show how the initial intermediate alkoxide first attacks the 2-position to cause an inversion of stereochemistry. Since the same process can then be repeated from the other direction (step 2), an equilibrium is eventually obtained where the preponderance of one isomer over the other is dictated by whatever other substituents may be present.

Henbest [ 4] has discussed a variety of reactions where the stereochemistry of the product is apparently controlled or influenced by the electrostatic effects of remote substituents. As an example, the isomer ratio of the steroid alcohols produced by reduction of a 12-keto function is sensitive to both the nature and configuration of a substituent at C(s) (p. 141). We may also cite the conversion of A -3-oxosteroids into their 4,5-epoxy-derivatives by alkaline hydrogen peroxide, where the proportion of /3-epoxy derivatives varies, according to substitution at C(iv>, from ca. 100% in the unsubstituted androst"4-en-3-one to 70% (- - 30% of a-epoxide) in the 17/ -hydroxy derivative. 

One of the most important asymmetric syntheses is the Sharpless epoxidation. In this reaction, an allylic alcohol is transformed, by reaction with rerf.-butyl hydroperoxide (TBHP) in the presence of titanium tetra-wo-propoxide (Ti(/-PrO)4) and diethyl tartrate (DET), to the corresponding epoxy alcohol, with high enantiomeric purity. By the application of either (+)- or (-)-DET, the reaction product with the desired stereochemistry can be obtained [1,2] (Scheme 1). "O" (-)-DET... 

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