Subject skeletal rearrangements

Dehydrations produce olehns from alcohols by the acid-catalyzed elimination of a water molecule from between two carbons. Acid-catalyzed dehydrations often give mixtures of products because the intermediate carbocation is prone to cationic rearrangements to more stable carbocations prior to formation of the olefin product. Moreover, even when the intermediate carbocation is not subject to skeletal rearrangement, as in file case of tertiary alcohols, mixtures of regioisomers are often produced during file loss of a proton from file carbocation. As a consequence, the acid-catalyzed dehydration of alcohols is generally not a viable synthetic method. 

The silver(I)-mediated electrocyclic ring opening of halocyclopropanes has been used to induce extensive skeletal rearrangements in gcm-dibromospiropentanes, providing rapid construction of naphthalenes and/or indenes (Scheme4.21 ).34 A variety of Lewis acids, Brpnsted acids, and solvent effects were carefully examined before optimal conditions were identified. It was found that subjection of spirocycle 60 to silver acetate in trifluoroacetic acid afforded rearrangement products 61 and 62 in moderate to good yields. The proposed mechanism of the reaction is illustrated in Scheme 4.21. 

The randomization of carbon and hydrogen atoms in benzene which occurs on electron impact 54) is analogous to the numerous skeletal rearrangements in the benzene series that occur upon photolysis.55,56) jiie rearrangements of the benzene molecule ion must proceed through structures that are related to known products of benzene photolysis, i.e., benz-valene, 38, prismane, 39, Dewar benzene, 40, and hexadienyne, 47. The open chain form of the benzene molecule ion, 41, has been a subject of... 

One aspect of this subject has been discussed in the context of D-homo-annulation reactions (p. 294), where the hydroxyl group is attached at the tertiary C(i7)-position in the pregnane series. A tertiary hydroxyketone which does not give a stable product of skeletal rearrangement may nevertheless undergo stereochemical inversion through two such reactions. This... 

Both intermolecular and intramolecular additions of carbon radicals to alkenes and alkynes continue to be a widely investigated method for carbon-carbon bond formation and has been the subject of a number of review articles. In particular, the inter- and intra-molecular additions of vinyl, heteroatomic and metal-centred radicals to alkynes have been reported and also the factors which influence the addition reactions of carbon radicals to unsaturated carbon-carbon bonds. The stereochemical outcome of such additions continues to attract interest. The generation and use of alkoxy radicals in both asymmetric cyclizations and skeletal rearrangements has been reviewed and the use of fi ee radical reactions in the stereoselective synthesis of a-amino acid derivatives has appeared in two reports." The stereochemical features and synthetic potential of the [1,2]-Wittig rearrangement has also been reviewed. In addition, a review of some recent applications of free radical chain reactions in organic and polymer synthesis has appeared. The effect of solvent upon the reactions of neutral fi ee radicals has also recently been reviewed. ... 

Matsuda and Sugishita found that cyclooctatetraene monoepoxide (233 equation 99) gave only skeletally rearranged products, e.g. (234), when treated with Grignard reagents. In an effort to isolate the presumed intermediate cycloheptatrienecarbaldehyde, (233) was subjected to a catalytic amount of MgBra, but this resulted in the formation of phenylacetaldehyde. 

The rearrangement of a-halo ketones under the influence of base was first described by Favorskii in 1892, and the general scope of the reaction and the mechanistic implications have been the subject of a number of reviews. In its most generally useful form, a-halo ketones undergo skeletal rearrangement when treated with a nucleophilic base (hydroxide, alkoxide or amine) to produce salts, esters and amides respectively (Scheme 1). With polyhalogenated ketones unsaturated acid derivatives are prcxluced, as shown in Scheme 2. 

The skeletal rearrangements of hydrocarbons represent an important class of reactions catalyzed by metal surfaces, which have few counterparts in homogeneous catalysis. Although two reviews dealing with the subject (7, 2) have recently been published, this review seemed worthwhile on account... 

Considerable efforts in the past have been devoted to the skeletal interconversion of alkaloids, if possible along biogenetic lines. Scott and coworkers have carried out numerous experiments in this area, and this work has been reviewed (162). The early work by Scott on the rearrangements of certain alkaloids, the subject of so much controversy, has been discussed elsewhere (2). 

Cluster skeleton rearrangements which can be studied by variable temperature NMR spectroscopy are of comparatively low energy and are often characterized by the presence of weak metal-metal interactions within the cluster core or a low-energy pathway between two polyhedra with similar relative energies. Although these low energy skeletal transformations are not the main subject of this article, some key examples will be briefly described. 

---