Benzyl derivatives Claisen

A combination of enzymatic resolution and orthoester rearrangement has been used by Brenna in a short synthesis of (R)-(-)-baclofen 503 (Scheme 6.79) [123a]. R) or (S)-3-Methyl-2-phenylbutylamine 506 were recently obtained using the same strategy (Scheme 6.79) [123bj. A Claisen-Johnson rearrangement of a benzyl vinyl ether studied by Raucher provided substituted arenes 510. Better results were observed with electron donating substituted arenes. This reaction has been extended to indole derivatives 511 (Scheme 6.79) [124]. 

A method for effecting ortho-Claisen rearrangements of benzyl vinyl ethers, reported last year (3, 189) has been extended to include furan, thiophen, and pyrrole derivatives, i.e. (100) (101). ... 

Reaction of 2-fluoro-3-trifluoromethylfurans 235 with allyl alcohols followed by Claisen rearrangement directly produced butenolides 237 [145, 146]. Oppositely, allyl mercaptane formed stable substitution product 236 [146], A similar transformation was reported for benzyl alcohols. While benzhydryl and (2-thienyl)methyl groups migrated at room temperature directly furnishing butenolides 239, in the case of benzyloxy derivatives, heating at 120 °C was required to reach the transformation. On the other hand, stable up to 140 °C products 238 were formed in the reaction of benzylamine, benzyl mercaptane, and 2-(hydroxymethyl)pyridine [147]. 

The Claisen rearrangement of benzyl vinyl ethers is not usually possible, so it is interesting to find that an ortho-Claisen rearrangement of ethyl mandelate derivatives can be effected (Scheme 29). Presumably this is due to the stabilizing influence of the ethoxycarbonyl group in the intermediate (135). Yields are in the range 20—80%, and the reaction can also be performed with 3-indolyl-glycolic esters. 

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