Steroids Favorskii rearrangement

Favorskii rearrangements, and other examples are known in the steroid nucleus (see below). Highly polar solvents (methanol or aqueous methanol) were originally used for these reactions the bromoketones may undergo dehydrobromination or substitution reactions in basic media of low polarity, such as pyridine or KOAc/HOAc. Recent work, however, has shown that sodium methoxide in aprotic solvents e.g. 1,2-dimethoxy-ethane) can be used, and tlxat the stereospecificity of various Favorskii reactions using simple alicyclic and aliphatic compounds is markedly dependent upon the nature of the solvent [301],... 

Relatively inaccessible cycloalkylcarboxylic acids can be produced via these Favorskii rearrangements (for example equation 7), and they have been especially useful for the introduction of alkyl groups at C-17 of the steroid nucleus. Thus the pregnenolones (10) and (11) can be converted into mixtures of rearrangement products (12) and (13), with the latter usually predominating in polar, protic solvents (Scheme... 

Iglesias-Arteaga and coworkers have reported several (diacetoxyiodo)benzene-promoted oxidative transformations of steroidal substrates (Schemes 3.148 and 3.149) [468 71]. In particular, the treatment of (25f )-3a-acetoxy-5p-spirostan-23-one (370) with (diacetoxyiodo)benzene in basic methanol leads to F-ring contraction via Favorskii rearrangement to afford product 371 (Scheme 3.148) [468],... 

The rearrangement with ring contraction probably is the most important synthetic application of the Favorskii reaction it is for example used in the synthesis of steroids. Yields can vary from good to moderate. As solvents diethyl ether or alcohols are often used. With acyclic a-halo ketones bearing voluminous substituents in a -position, yields can be low a tcrt-butyl substituent will prevent the rearrangement. 

In 1894, Alexie Favorskii published an early account of the rearrangement of simple acyclic a-halo ketones. This was followed in subsequent years with additional reports/ In 1914, he published the cyclic version featuring the ring contraction of 2-chlorocyclohexanone. This modification makes this transformation a reliable way to sjmthesize 1-substituted cycloalkane carboxylic acid derivatives. Later in the century, the rearrangement found application in the modification of steroids. Only in the last half of the 20 century has a clearer picture of the mechanism appeared. ... 

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