Epoxide opening rearrangement

Domino reactions are also used in the development of new and potent pharmaceuticals, which is an important target in organic synthesis. The following example by Katoh and coworkers presents an impressive approach to the tetracyclic core structure of the novel anti-influenza A virus agent, stachyflin (1-152), using as key feature a new Lewis acid-induced domino epoxide-opening/rearrangement/cy-... 

Scheme 1.38. Domino epoxide-opening/rearrangement/cydization reaction towards the total synthesis of (+)-stachyflin (1-152).

More remote substituents may also participate in epoxide opening/rearrangement. Christol and coworkers examined several S,(6)-substituted-2,3-norbomene ejco-oxides under acidic conditions, and found that certain 5-endo substituents played a part in oxirane opening. For example, oxa rings were formed in reactions of substrates bearing 5-entfo-methoxycarbonyl or -hydroxymethyl groups. A novel 1,4-migration of chloride was also detected (equation 28). ... 

Scheme 5. Payne rearrangement/epoxide opening reaction hydroxide nucleophile.

A careful analysis of this problem led to the identification of an exceedingly simple solution (see Scheme 10). The Masamune-Sharpless solution to the threo 2,3-diol problem actually takes advantage of the ready availability of the erythro 2,3-diol diastereoisomer. As we have seen in Scheme 9, erythro 2,3-diols such as 20 can be conveniently assembled from trans allylic alcohols via sequential SAE and Payne rearrangement/epoxide opening reac-... 

Efficient synthesis of the mycotoxin asteltoxin 189 was accomplished beginning with the cycloaddition between 3,4-dimethylfuran and 3-benzyloxypropanal, which furnished pho-toaldol 183 in 63% yield (Scheme 42)84. Epoxidation from the convex face of this adduct, with subsequent epoxide opening, afforded 184, which was then elaborated through a series of steps to 185. The side chain was introduced via lithiosulfoxide 186 to furnish, after double sigmatropic rearrangement, 187. Hydrolysis of this afforded 188, which was oxidized and elaborated to 189 in two steps. 

Based on the labeling experiments, a plausible mechanism involving mthenium vinylidene intermediates SS is proposed in Scheme 6.21. Cydization of this vinylidene intermediate leads to the formation of the epoxy carbenium 56, which then undergoes an epoxide opening to form l,4-dien-3-ol 57. A subsequent pinacol rearrangement of this alcohol furnishes ketone 58, providing the required skeleton for the observed phenol product 54. 

For the very first report of a C- to O-silyl rearrangement occurring after epoxide opening with 2-TMS-l,3-dithiane, see P. F. Jones, M. F. Lappert, A. C. Szary, Journal of the Chemical Society, Perkin Transactions l 1973, 2272... 

Disubstituted furans (130) can be obtained by treatment of j8-alkoxy- and j8-arylthio-a,j8-unsaturated ketones, for example 3-methoxy-l-phenyI-2-buten-l-one (128) or 3-ethylthio-l-phenyl-2-buten-l-one (129), with dimethylsulfonium methylide (79JHC815, 69TL679). The possible reaction pathway (Scheme 27) shows the initially formed epoxides as rearranging by ring opening at the tertiary epoxide carbon atom. 

A more exciting example is the epoxide 56 of natural a-pinene 55 that rearranges to the unsaturated aldehyde 57 in excellent yield.11 Epoxide opening to give the more substituted carbocation is followed by rearrangement 59 and then fragmentation 58. Note that the expansion of the strained four-membered ring is preferred to any alternatives. 

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