Quasi-Favorskii hydroxide

The quasi-Favorskii rearrangement has been used often in the synthesis of unnatural, conplex, polycyclic structures. Indeed, this method is uniquely suited for such targets. However, undesired side reactions can occur. An exanple, discussed here within its mechanistic context, is based on a report by Ueda and coworkers. They treated the polycyclic dibrominated diketone 37 with potassium hydroxide in the expectation of obtaining cubane-l,3-dicarboiq lic acid 38. Given what was known about quasi-Favorskii reactions at the time (vide supra), the plan made perfect sense. However, exposure of 37 to 5% KOH for 15 min at 80 °C afforded not 38 but the cyclopropyl lactone 43 fScheme 7.12). A proposed mechanism for the process began with a Haller-Bauer cleavage, always a potential risk in quasi-Favorskii... 

Certain cycloaddition/cyclization processes produce substrates for the quasi-Favorskii rearrangement with good yield and selectivity. For example, the intramolecular cycloaddition of ketene 45, available by dehydrohalogenation of the corresponding acid halide 44, afforded 46 in moderate yield (Scheme 7.131. This conpound reacted smoothly with lithium hydroxide under mild conditions to form the carboxylic acid 47. ... 

It is known that a-halocyclobutanones react via a quasi-Favorskii mechanism to produce ring contraction products. Indeed, treatment of 49-51 with sodium hydroxide resulted in the formation of products 52-54, respectively. The mild reaction conditions are noteworthy, as is the fact that the overall process makes 48 a functional equivalent of 55 as a dienophile in the... 

A single example was given in the same paper on the intramolecular Diels-Alder reaction of a regioisomeric halocyclobutenone. Treatment of the alcohol 56 with BF3-Et20 resulted in the formation of 57, which could be observed by NMR and underwent cycloaddition to afford 58 fScheme 7.1ST The crude product was treated with hydroxide to afford the quasi-Favorskii product 59 in 27% overall yield. The particular dienophile/quasi-Favorskii combination used in this case is the functional equivalent of dienophile 60. 

---