Unsaturated ketones, acyl migrations

Ion 21 can either lose a proton or combine with chloride ion. If it loses a proton, the product is an unsaturated ketone the mechanism is similar to the tetrahedral mechanism of Chapter 10, but with the charges reversed. If it combines with chloride, the product is a 3-halo ketone, which can be isolated, so that the result is addition to the double bond (see 15-45). On the other hand, the p-halo ketone may, under the conditions of the reaction, lose HCl to give the unsaturated ketone, this time by an addition-elimination mechanism. In the case of unsymmetrical alkenes, the attacking ion prefers the position at which there are more hydrogens, following Markovnikov s rule (p. 984). Anhydrides and carboxylic acids (the latter with a proton acid such as anhydrous HF, H2SO4, or polyphosphoric acid as a catalyst) are sometimes used instead of acyl halides. With some substrates and catalysts double-bond migrations are occasionally encountered so that, for example, when 1 -methylcyclohexene was acylated with acetic anhydride and zinc chloride, the major product was 6-acetyl-1-methylcyclohexene. ... 

The Oxa Di-n-methane Reaction and Related Processes - A detailed examination of the triplet and singlet state reactions of a series of P,y-unsaturated enones has been reported. Many examples are cited and are typified by the conversion of the enone (140) into (141) on sensitized irradiation. This reaction is a typical example of the well known oxa-di-n-methane process, which fundamentally involves a 1,2-migration of the acyl group. Direct irradiation populates the singlet state of the enone (140) and this yields (142) by a 1,3-acyl migration. The oxa-di-n-methane reaction of chiral bicyclo[2.2.2]oct-5-en-2-one systems has been used as a path to tricyclic ketones. 

The acylation of alkanes has also been known for a long time, but for synthetic purposes is limited to simple substrates. The initial step is hydride abstraction by an acylium ion, a process well established in the presence of a powerful Lewis acid, most commonly an aluminum halide, or strong protic acid. The carbocation so formed can then undergo elimination, possibly after hydride or alkyl migration, to give an alkene which is then acylated. In the presence of excess alkane, saturated ketones are formed by a further intermolecular hydride transfer, whereas with an excess of acyl halide, the product is the (conjugated) unsaturated ketone. -" The synthetic potential is obviously likely to be limited to simple substrates. 

The photochemical 1,3-acyl migration which converts certain jSy-unsaturated ketones into isomeric enones has been investigated for a series of compounds, including cholest-4-en-7-one (651) and its 6,6-dimethyl derivative (652). Photoequilibration affords the isomers (653), considered to arise via n — tt triplet states. The reactions are influenced by conformational and conjugative features which effect the stability of an intermediate radical pair of the type (654). Other workers have studied the phosphorescence spectra and lifetimes of triplet excited states of a number of j y-unsaturated ketones, including some... 

Heteroatom-stabilized Carbanions. Heteroatom-stabilized and allylic carbanions serve as homoenolate anions and acyl anion equivalents, e.g. a-anions of protected cyanohydrins of aldehydes and Q ,/3-unsaturated aldehydes are intermediates in general syntheses of ketones and Q ,/3-unsaturated ketones (eq 36). Allylic anions of cyanohydrin ethers may be a-alkylated (eq 37) or, if warmed to —25°C, may undergo 1,3-silyl migration to cyanoenolates which may be trapped with TMSCl. Metalated Q -aminonitriles of aldehydes are used for the synthesis of ketones and enamines (eq 38). Similarly, allylic anions from 2-morpholino-3-alkenenitriles undergo predominantly a-C-alkyl-ation to give, after hydrolysis, a,/3-unsaturated ketones (eq 39). ... 

Although the mechanism for the formation of acetylcyclohexane is known, an alternative mechanism is proposed here for the acylation of cyclohexene with acetyl chloride. In this reaction, after the acyl cation adds to double bond, the elimination of the a-proton gives an a,)0-unsaturated ketone, whereas the attack of chloride produces a 0-chloroketone. Since acetyl is an electron-withdrawing group, it is plausible that the positive charge migrates to form a more stable carbocation, which electrophilically alkylates with benzene. 

During the course of these synthesis, the synthesis of 19,20-dehydroyohimbines was also achieved by using the acylated D/E-cis enone, which has a folded ring conformation. On the other hand, the 19,20-unsaturated ketone has a rather planar structure. Therefore, it was expected that the back migration of a double bond at the 18,19-position into the 19,20-position would occur. Actually, acid treatment of the 18,19-enone yielded the 19,20-enone in an excellent yield. Subsequent reductions furnished the first total synthesis of three 19,20-dehydroyohimbines. 

Some p,y-unsaturated ketones undergo both 1,2- and 1,3-acyl migrations in photoexcitations. For example, l,2-dimethylcyclopent-2-enyl methyl ketone 76 gives 77 and 78. 

The photochemistry of carbonyl compounds has been one of the main areas of research in organic photochemistry for many years. Among aU the different types of carbonyl compounds, P,y-unsaturated ketones have been the subject of extensive studies. The results obtained from these efforts, conducted over a 30-year period, show that, in general, direct irradiation of P,y-unsaturated ketones yields products resulting from 1,3-acyl migration, while triplet-sensitized reactions of these compounds affords cyclopropyl ketones by oxa-di-n-methane (ODPM) rearrangement pathways. Alternative reaction routes, such as decarbonylation, ketene formation, epimerization, [2+2]-intramolecular cycloadditions, Norrish Type I and Norrish Type II reactions, cis-trans isomerizations, and reductions of the C-C double bond, have also been described in some instances, depending on some particular structural features present in the P,y-unsaturated ketone. However, the photoreactivity of these compounds is dominated by the two main processes mentioned above. 

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