Benzilic ring contraction

The benzilic acid rearrangement of steroid a-diketones is often the preferred method for ring contraction. Yields are generally excellent, and in several instances the reaction has been shown to be stereospecific. Preparation of the starting a-diketones is discussed below and illustrated with several excellent experimental procedures. 

In practice, the scope of the benzilic rearrangement as a tool for the ring contraction of steroids is defined by the availability of a-diketones, or the corresponding diosphenols. 

Ring contraction by benzilic acid rearrangement of a-diketones... 

The formation of this dicarboxylic acid derivative is of some interest. The free ligand quinone is known to undergo a benzilic acid rearrangement with concomitant ring contraction, followed by decarboxylation to yield a diazafluoreneone on treatment with base (Fig. 8-42). 

The benzilic rearrangement of an o-quinone results in ring contraction. Among the earliest recorded examples is the synthetically useful conversion of phenanthroquinones into 9-hydroxyfluorenecarboxylic acids (equation As with the benzilic acids, compounds such as (28) are susceptible to oxidative... 

The cyclopentapyrazoles (45 R = H, Me) are obtained in 67% and 54% yields, respectively, by benzilic acid rearrangement of the corresponding indazolediones (44). This ring contraction has many analogs in the next section, and may occur during alkaline permanganate oxidations of suitable substrates. For example, oxidation of fuscinic acid dimethyl ether (46) affords (48) and (49), implicating the a-diketone (47) as a common intermediate. ... 

In the benzil-benzilic acid rearrangement, an a-diketone is treated with a base to give the sodium salt of an a-hydroxy carboxylic acid. In the Favorskii rearrangement, an a-halogenoketone is treated with an alkoxide anion to give the a-alkyl ester. This reaction may also be used to effect a ring contraction. 

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. 

Interest in the structure-activity relationships of the gibberellins has led to the partial synthesis of the four stereoisomers about positions 5 and 6 of the hexa-hydrofluorene (57). The unsaturated acid anhydride (56) was prepared by the benzilic acid ring-contraction of the 6,7-diketones obtained from oxidation of desisopropyl dehydroabietic acid, and converted into the saturated acids by reduction and base-catalysed epimerisation. 

One example has been given of a potentially useful version of the benzil-benzilic acid rearrangement in which a-acetoxy-ketones (41), obtained by Pummerer rearrangement of the corresponding a-thio-ketone, undergoes ring contraction to give the a-hydroxy-acid (42), a... 

The Chemistry of Ring B.—The conformation of ring B of some aromatic diterpenoids has been studied. The C-6-C-7 proton coupling constants for a series of acetoxy-alcohols have been determined. These led to the conclusion that ring b exists in a half-boat conformation (49). The 6,7-diketone-benzilic acid ring-contraction sequence has been applied to some ring c bromo-derivatives of abietic acid. 

This reaction has general application for preparing benzilic acids and their esters which have important biological activities. The formed benzilic acid can be used as reducing reagent to transform Qf, -unsaturated ketones into saturated ketones.In addition, the benzilic acid rearrangement on cyclic of-diketones will lead to ring contracted products 2ii, 2kk, 2nn... 

Ring contraction of the dichloro-ketone (436), using powdered NaOH under aprotic conditions (THF solvent), gave the semi-benzilic acid product (437 89%) and the cyclohexanecarboxylic acid (438 11 %). In protic media e.g. 95 % aqueous THF) the proportions of (437) and (438) were appreciably altered. 

Schaltegger et al reported the base-catalysed benzilic acid rearrangement of cyclic diketone 29, which, resulted in ring contraction affording the acid 30. 

Stereospecific benzilic acid rearrangement Ring contraction of isocyclics... 

Spiro(adamantane-2,2 -adamantane) (223) has been synthesized from diketone (224) by selenium dioxide oxidation and ring-contraction by a benzilic acid rearrangement and also from (225), which is obtained by rearrangement of (226). Also noted are C-labelling studies which show that Wolff... 

Several examples are known of the contraction of steroid rings by benzilic acid rearrangements of a -diketones [2g2]. Acyloin rearrangements in the steroid field, particularly in the conversion of i7-hydroxypregnan-20 ones into D-homo-ketols,... 

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