Payne rearrangement stereospecificity

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... 

A novel regioselectivity is observed with rrans-2,3-epoxy alcohols. The C-1 attack of 1,2-epoxy alcohol formed by the Payne rearrangement proceeds predominantly, and anri-p,7-dihydroxyalkynes are obtained stereospecific ly (equation 37). ° The reaction is employed in the synthesis of a pheromone, eO fA o-6-acetoxyhexadecan-5-olide. 

It is noteworthy that the Payne rearrangement proceeds in a stereospecific manner, providing clean inversion of stereochemistry at the central 2-position as a result of an intramolecular SN2-type mechanism Thus, both configurations at this site are readily available from the same starting material by appropriate control of the rearrangement. 

Application of the aza-Payne rearrangement was reported for the construction of highly substituted pyrrolidines starting from allqmylated aziridinemethanols as the substrates.Thus, as described in Scheme 10.4. treatment of the stereospecifically prepared syn-16 in the case of R, H with dimethylsulfoxonium methylide initiated the structural transposition to furnish the intermediary all yl epoxide lnt-2 which further cyclized to epoxy pyrrolidine 17 in a one-pot manner. Aldiou die diastereomeric anti-16 experienced the same rearrangement, but the following cyclization was not possible due to trans relationship between the reacting two units. 

Smooth and essentially stereospecific transformation was realized for the following Payne rearrangements of the (E)-92 substrates. The limited (29%) conversion of (E)-syn-92e (Table 10.2. entry 4) reflects the presence of a tertiary carbon direcdy attached to the epoxide three-membered ring in the corresponding product (Z)-anti-93e, affording significant steric repulsion with the trifluoromethyl-containing epoxide substituent. In the case of the substrates (E)-anti-92d and (E)-syn-92d, contamination of the desired product with about 15% of unidentified materials was detected, but formation of these byproducts was nicely suppressed by the addition of 3 equiv. of EtOH to the reaction mixture. 

The isomerization of 2,3-epoxy alcohol 1 under the influence of a base to l,2-epoxy-3-ol 2 is referred to as Payne rearrangement. It involves an equilibrium of the epoxy alcohol 1 with the isomeric 2 and the reaction is stereospecific, proceeding with inversion of configuration at C-2 carbon of the epoxide ring via Sn2 t5q>e mechanism. 

Aldonolactones activated at the primary position very rapidly form a primary epoxide of the open aldonic acid when dissolved in aqueous base. Usually, 3 molar equivalents of potassium hydroxide are used to keep the pH above 14. This is a prerequisite for a Payne rearrangement and/or for opening of the epoxide by an intramolecular nucleophile. Using the weaker base potassium carbonate, no rearrangement will take place and hence the primary epoxide will be opened at the primary carbon by hydroxide. Pentonolactones activated at C-5 will isomerise stereospecifically at C-4 when treated with strong potassium hydroxide. This is due to the opening of the primary epoxide by the carboxylate... 

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