Epoxy alcohols, Payne rearrangement

On alkaline treatment of the 3,3-dimethyl glycidol, Payne rearrangement takes place. In alkaline aqueous solutions, 2,3-epoxy alcohols are in equilibrium with the corresponding 1,2-epoxy alcohols. Payne was the first to observe this... 

Sharpless and Masumune have applied the AE reaction on chiral allylic alcohols to prepare all 8 of the L-hexoses. ° AE reaction on allylic alcohol 52 provides the epoxy alcohol 53 in 92% yield and in >95% ee. Base catalyze Payne rearrangement followed by ring opening with phenyl thiolate provides diol 54. Protection of the diol is followed by oxidation of the sulfide to the sulfoxide via m-CPBA, Pummerer rearrangement to give the gm-acetoxy sulfide intermediate and finally reduction using Dibal to yield the desired aldehyde 56. Homer-Emmons olefination followed by reduction sets up the second substrate for the AE reaction. The AE reaction on optically active 57 is reagent... 

It is appropriate at this juncture to address some of the more useful transformations of 2,3-epoxy alcohols.913 A 2,3-epoxy alcohol such as compound 14 possesses two obvious electrophilic sites one at C-2, and the other at C-3. But in addition, C-l of a 2,3-epoxy alcohol also has latent electrophilic reactivity. For example, exposure of 14 to aqueous sodium hydroxide solution results in the formation of triol 19 in 79% yield (see Scheme 5). In this interesting transformation, hydroxide ion induces the establishment of an equilibrium between 2,3-epoxy-l-ol 14 and the isomeric 1,2-epoxy-3-ol 18. This reversible, base-induced epoxide migration reaction is a process known as the Payne rearrangement.14... 

As well as the Payne rearrangement, 2,3-epoxy alcohols and some of their derivatives show some other interesting rearrangement procedures that often constitute key steps in syntheses of complex molecules. 

In the Payne rearrangement, a 2,3-epoxy alcohol is converted to an isomeric one, by treatment with aqueous base ... 

Payne rearrangement. The Payne rearrangement2 of a primary cts-2,3-epoxy alcohol to a secondary 1,2-epoxy alcohol usually requires a basic aqueous medium, but it can be effected with BuLi in THF, particularly when catalyzed by lithium salts. As a consequence, the rearrangement becomes a useful extension of the Sharpless epoxidation, with both epoxides available for nucleophilic substitutions. Thus the more reactive rearranged epoxide can be trapped in situ by various organometallic nucleophiles. Cuprates of the type RCu(CN)Li are particularly effective for this purpose, and provide syn-diols (3).3... 

Although the Payne rearrangement usually produces mixtures of epoxy alcohols, because the rate of reaction of 2 with any given nucleophile is faster than that of i, the l,2-epoxy-3-alcohols generated in situ can be selectively and irreversibly captured by a nucleophile to afford 3. 

Asymmetric epoxidation of 10a under standard conditions yields the crystalline epoxy alcohol 2a in 95% ee (91% chemical yield). Treatment of 9a with thioanisol in 0.5N NaOH, in rerf-butyl alcohol solution, gives -after protection of the hydroxyl groups as benzyl ethers- the sulfide a (60% overall yield) through an epoxide ringopening process involving a Payne rearrangement. Since the sulfide could not be hydrolysed to the aldehyde 7a without epimerisation at the a-position, it was acetoxylated in 71% yield under the conditions shown in the synthetic sequence (8a... 

Cyclization of halohydrins 0-16 Cyclization of 1,2-diols 0-18 Payne rearrangement of 2,3-epoxy alcohols... 

Epoxy-3-alcohols can be derived from 2,3-epoxy-1-alcohols by the base-catalyzed Payne rearrangement as illustrated in step d of Figure 6A.4 [59,64], The rearrangement is completely stereospecific but, because it is reversible, it usually results in an equilibrium mixture of the two epoxy alcohols for which the relative proportions are structure-dependent. Practical synthetic applications of this rearrangement therefore depend on methods that will shift the equilibrium completely in the direction desired. Nucleophiles such as thiolates and amines are... 

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]. 

A key reaction of 2,3-epoxy alcohols is the Payne rearrangement, an isomerization that produces an equilibrium mixture. This rearrangement then allows for the selective reaction with a nucleophile at the most reactive, primary position (Scheme 9.5).18,84... 

Under Payne rearrangement conditions, sodium /-butylthiolate provides 1 -/-butylthio-2,3-diols with very high regioselectivity. The selectivity is affected, however, by many factors including reaction temperature, base concentration, and the rate of addition of the thiol. These sulfides can then be converted to the l,2-epoxy-3-alcohols, which in turn react with a wide variety of nucleophiles specifically at the 1-position (Scheme 9.6). This methodology circumvents the problems associated with the instability of many nucleophiles under Payne conditions.85... 

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.

Glycidol, like all 2,3-epoxy alcohols, is susceptible to the Payne rearrangement when exposed to base. Payne rearrangement of (/ )-or (S)-glycidol is degenerate consequently racemization does not occur. 

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