Epoxy alcohols rearrangements

Morgans, D. J. Sharpless, K. B. Traynor, S. G. Epoxy alcohol rearrangements hydroxyl-mediated delivery of Lewis add promoters./. Am. 

Payne further investigated the scope and limitations of the epoxy alcohol rearrangement under the standard conditions depicted in Scheme 10.1. A major quantity of 3 was found to be readily transformed to the isomeric 4, attaining an equilibrium ratio of 3 4 = 8 92. The position of equilibrium for this structural transposition was further probed by using representative isomeric substrates thus, only a small amount of anti-6 was obtained from (E)-5, while the diastereomeric syn-6 was formed from (Z)-5 as a mixture of syn-6 (Z)-5 = 42 58 after 1 h at ambient temperature. The same situation was noticed for (E)-7, which afforded anti-S in a ratio of E)-7 anti-6 = 44 56, and (Z)-7, which was preferentially converted to syn-8, leaving only 5% of (Z)-7 in the mixture. 

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... 

Titanium-IV compounds with their Lewis acid activity may catalyze an interfering rearrangement of the starting allylic alcohol or the epoxy alcohol formed. In order to avoid such side-reactions, the epoxidation is usually carried out at room temperature or below. 

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 a formal synthesis of fasicularin, the critical spirocyclic ketone intermediate 183 was obtained by use of the rearrangement reaction of the silyloxy epoxide 182, derived from the unsaturated alcohol 180. Alkene 180 was epoxidized with DMDO to produce epoxy alcohol 181 as a single diastereoisomer, which was transformed into the trimethyl silyl ether derivative 182. Treatment of 182 with HCU resulted in smooth ring-expansion to produce spiro compound 183, which was subsequently elaborated to the desired natural product (Scheme 8.46) [88]. 

Scheme 8.45 Suzuki-Tsuchihashi rearrangement of epoxy alcohol derivatives.

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

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. 

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... 

Scheme 44 Electrochemically induced Hofmann rearrangement with insertion of an epoxy alcohol.

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... 

The full paper on the synthesis of onikulactone and mitsugashiwalactone (Vol. 7, p. 24) has been published.Whitesell reports two further useful sequences (cf. Vol. 7, p. 26) from accessible bicyclo[3,3,0]octanes which may lead to iridoids (123 X=H2, Y = H) may be converted into (124) via (123 X = H2, Y = C02Me), the product of ester enolate Claisen rearrangement of the derived allylic alcohol and oxidative decarboxylation/ whereas (123 X = 0, Y = H) readily leads to (125), a known derivative of antirride (126) via an alkylation-dehydration-epoxi-dation-rearrangement sequence. Aucubigenin (121 X = OH, R = H), which is stable at —20°C and readily obtained by enzymic hydrolysis of aucubin (121 X = OH, R = j8-Glu), is converted by mild acid into (127) ° with no dialdehyde detected sodium borohydride reduction of aucubigenin yields the non-naturally occurring isoeucommiol (128 X=H,OH) probably via the aldehyde (128 X = O). ... 

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