Rearrangements Favorskii, ring contraction

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. 

Diastereoselective Favorskii ring contraction. Bicyclic a-chloro-8-lactams can undergo highly diastereoselective ring contraction to proline derivatives when treated with base, preferably barium hydroxide in aqueous solution. Thus 1 is converted into 2 and 3 in the ratio 9 1. The ring contraction of 4 to 5 is stcreospecific. in contrast, rearrangement... 

In order to distinguish between a mechanism proceeding via a symmetrical cyclopropanone intermediate (Favorskii reaction) and a mechanism closely related to the benzilic acid rearrangement and called semibenzilic (or quasi-Favorskii) rearrangement, the ring contraction of 2-bromocyclobutanone was studied in deuterium oxide using sodium carbonate as base (50 C) or in boiling deuterium oxide only. 

The Favorskii rearrangement has frequently been employed in ring contractions. For example, a Favorskii ring contraction was employed in the synthesis of the cage compound 12 en route to a hexacyclotetradecane, and of cage compound 14 en route to pentaprismane. ... 

Favorskii ring contraction of ketone 22 followed by diastereoselective protonation led to ester 23, an intermediate in the synthesis of structures related to the guanacastepene core. In this case, an epoxide served as the leaving group. Favorskii rearrangements of various a,p-epoxyketones have been investigated. ... 

The examples presented illustrate two of the common ways Favorskii rearrangements are run. The first is a large scale Favorskii ring contraction. The second illustrates the use of the Favorskii rearrangement to form sterically congested carbon frameworks. 

Within the cubane synthesis the initially produced cyclobutadiene moiety (see p. 329) is only stable as an iron(O) complex (M. Avram, 1964 G.F. Emerson, 1965 M.P. Cava, 1967). When this complex is destroyed by oxidation with cerium(lV) in the presence of a dienophilic quinone derivative, the cycloaddition takes place immediately. Irradiation leads to a further cyclobutane ring closure. The cubane synthesis also exemplifies another general approach to cyclobutane derivatives. This starts with cyclopentanone or cyclohexane-dione derivatives which are brominated and treated with strong base. A Favorskii rearrangement then leads to ring contraction (J.C. Barborak, 1966). 

Another useful route to cyciopentanes is the ring contraction of 2-bromo-cydohexanones by a Favorskii rearrangement to give csrdopcntanecarboxylic acids. If a 0 dibromoketones are used, ring opening of the intermediate cydopropanone leads selectively to, y-unsaturated carboxylic acids (S.A, Achmad, 1963, 1965 J. Wolinsky, 1965). 

With cyclic a-halo ketones, e.g. 2-chloro cyclohexanone 6, the Favorskii rearrangement leads to a ring contraction by one carbon atom. This type of reaction has for example found application as a key step in the synthesis of cubane by Eaton and Cole for the construction of the cubic carbon skeleton ... 

RING CONTRACTION via A FAVORSKII-TYPE REARRANGEMENT CYCLOUNDECANONE... 

As usual, the key to this problem is numbering correctly. The main question is whether the ester C in the product is C3 or C4. Because a ring contraction from 6- to 5-membered is likely to proceed by a Favorskii rearrangement, where the last step is cleavage of a cyclopropanone, it makes sense to label the... 

This reaction is known as the Favorskii rearrangement,37 If the ketone is cyclic, a ring contraction occurs. 

The Favorskii reaction has been used to effect ring contraction in the synthesis of strained ring compounds. Entry 4 in Scheme 10.3 illustrates this application of the reaction. With 7,7 -dihalo ketones, the rearrangement is accompanied by dehydrohalo-genation to yield an a,/ -unsaturated ester, as illustrated by entry 3 in Scheme 10.3. 

The Favorskii rearrangement results from the action of base on an a-halo ketone. When applied to cyclic ketones, ring contraction results, as shown in the classic case of cyclohexanone formulated below. 

The acid hydrolysis of cyclopropanone ethylene ketals to the corresponding esters appears to be a facile, high yield reaction (75—90%) which may be of synthetic importance. Thus, as shown in Scheme 29, a ring contraction similar to a Favorskii rearrangement may be achieved under mildly acidic conditions.107)... 

Treatment of (25 W)-3 -accloxy-5/3-spiroslan-23-onc (16) with diacetoxyiodobenzene in KOH-MeOH and diacetoxyiodobenzene gave F-ring contraction via Favorskii rearrangement to (225,23/f,25/f )-23-methoxycarbonyl-22,26-epoxy-24-nor-5/3-furos tan-... 

Cyclopropanone cleavage with elimination 72 can also lead to ring contraction as in the synthesis of the trans acid 74 from natural pulegone13 70. Bromination gives the unstable dibromide 71 that is immediately treated with ethoxide to initiate the Favorskii rearrangement. The product is a mixture of cis and trans isomers of the ester 73 but hydrolysis under vigorous conditions (reflux in aqueous ethanol) epimerises the ester centre and gives exclusively the trans acid 74. 

Favorskii rearrangement of cyclic 2-bromoketones leads to ring contraction and this has become one of the most fruitful uses of the rearrangement in synthesis. Bromination of cyclohexanone is a simple reaction (Chapter 21) and treatment with methoxide gives the methyl ester of cyclopentane carboxylic acid in good yield. 

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