Favorskii ring contraction

The single Favorskii ring contraction of 1,5-dibromoadamantane-2,6-dione (55) also enables the preparation 3-substituted noradamantanes as illustrated in Eq. (40) 126>. Unfortunately, the starting material, 55, is diffi-... 

Favorskii ring contractions of 1,3-dibromoadamantane-2,6-dione (55)121 12a) also provide synthetic approaches to bisnoradamantane derivatives as illustrated in Scheme 13. 

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... 

The Baeyer-Villiger oxidation has been utilized as an element of several novel functional group manipulations. Suginome and Yamada converted adamantanone (64) to 2-thiaadamantane (66) via the lactone (65 Scheme 19). Eaton et al.P in the synthesis of pentaprismane (70) from homopentaprismanone (67 Scheme 20), required that a leaving groiq) be introduced a to the carbonyl group in or r to carry out a Favorskii ring contraction. Oxidation of (67) afforded lactone (68), which was converted in several steps to the requisite hydroxy ketone (69). 

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. 

The key step in this synthesis is the Favorskii ring contraction of the a-chlorocyclohexanone (61) to the cyclopentane via the intermediate cyclopropanone 63. 

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 ... 

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. 

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

Two types of ring contractions have been used in the synthesis of pyrrolidines. The older one, an analogous Favorskii process, is the key step of Honjo s a-allokainic acid synthesis. The general lines of this approach are given in Scheme 29 (173). 

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)... 

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