Substrates Favorskii rearrangement

We see from these examples that many of the carbon nucleophiles we encountered in Chapter 10 are also nucleophiles toward aldehydes and ketones (cf. Reactions 10-104-10-108 and 10-110). As we saw in Chapter 10, the initial products in many of these cases can be converted by relatively simple procedures (hydrolysis, reduction, decarboxylation, etc.) to various other products. In the reaction with terminal acetylenes, sodium acetylides are the most common reagents (when they are used, the reaction is often called the Nef reaction), but lithium, magnesium, and other metallic acetylides have also been used. A particularly convenient reagent is lithium acetylide-ethylenediamine complex, a stable, free-flowing powder that is commercially available. Alternatively, the substrate may be treated with the alkyne itself in the presence of a base, so that the acetylide is generated in situ. This procedure is called the Favorskii reaction, not to be confused with the Favorskii rearrangement (18-7). ... 

In most cases, fluorinated substituents, when not directly placed at the reaction center, do not influence much the rearrangement routes [7] Favorskii rearrange ment of a substrate bearing a tnfluoromethyl group proceeds as expected [46] (equation 10)... 

When the Favorskii rearrangement is carried out on a substrate which contains an internal nucleophile, this can attack the cyclopropanone intermediate to yield cyclic products. The reaction shown in Scheme 13 provides a route to polysubstituted "y-butyrolactones by this kind of mechanism. 

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],... 

In principle, any reaction that results in the placement of a leaving group next to a carbonyl provides a method to prepare substrates for the quasi-Favorskii rearrangement. Substrates include ketones that might be candidates for a normal Favorskii rearrangement, because even these conpounds can undergo a quasi-Favorskii reaction under the right circumstances, as illustrated later in this chapter. 

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. ... 

Kraus and Shi used condensation reactions for the assembly of precursors to the quasi-Favorskii rearrangement. Reaction of the bromoketoester 83 with ethylamine and formaldehyde gave 84, the result of a double Mannich reaction fScheme 7.22T Under acidic conditions, methyl vinyl ketone combined with 83 to give the annulation product 87. Each of these products, 84 and 87, was a good substrate for the quasi-Favorskii rearrangement. Ketone 84 reacted with the enolate of acetylcyclohexene (85) to produce 86 in 60% yield. Ketone 87,... 

A starting point for the synthesis was ketone 212, readily available through a sequence that involved one thermal and two photochemical cycloadditions. The object of the first set of transformations shown in Scheme 7.47 was to prepare a substrate suitable for the quasi-Favorskii rearrangement. To that end, a Baeyer-Mlliger oxidation was accomplished with mCPBA. This was followed by a CH oxidation with RUO4, saponification, and ester formation... 

This chapter s final example of caged hydrocarbon synthesis is one that further eii5)hasizes the importance of cycloaddition reactions in creating substrates for the quasi-Favorskii rearrangement. This synthesis also showed, as many polycyclic hydrocarbon syntheses have, the limits that exist in intramolecular photochemical [2+2]-cycloaddition processes. 

Figure 7.11 Possible substrates for the quasi-Favorskii rearrangement.

More recent work on the Favorskii rearrangement has focused on testing the ability of increasingly complex substrates to participate in Favorskii and related rearrangements. Efforts have also been directed at determining how reaction conditions affect the precise mechanism of Favorskii rearrangements. Both of these aspects of the Favorskii rearrangement will be discussed in subsequent sections. 

When the cyclic substrate has an equatorial halogen (Table 2, step A), the experiment shows that the enolization at the a position does not lead to epimerization. This again is in perfect agreement with the stereoelectronic control which favors fixation of the deuterium by the enolate in the axial direction. This enolization does not seem to have any further influence on the Favorskii rearrangement. ... 

In these constrained molecules, the Favorskii rearrangement leads essentially to the ring-contracted acid or ester in good yields. However, the formation of ring-opened products has been reported when polyhalogenated strained ketones react according to the quasi-Favorskii mechanism. Results using this type of substrate are reported in Table 8. 

The comparative analysis of the development of the Favorskii rearrangement mechanism in cyclohexane and constrained polycyclic substrates allows... 

Three steps transform (5)-carvone 7 into the a-chloro-cyclohexanone derivative 8. The Favorskii rearrangement on this substrate leads stereoselectively to the highly... 

The Favorskii rearrangement also takes place from substrates other than a-haloketones as long as the intermediate cyclopropanone ring can be formed. For example, the... 

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