Tautomerization unsaturated ketones

An interesting case are the a,/i-unsaturated ketones, which form carbanions, in which the negative charge is delocalized in a 5-centre-6-electron system. Alkylation, however, only occurs at the central, most nucleophilic position. This regioselectivity has been utilized by Woodward (R.B. Woodward, 1957 B.F. Mundy, 1972) in the synthesis of 4-dialkylated steroids. This reaction has been carried out at high temperature in a protic solvent. Therefore it yields the product, which is formed from the most stable anion (thermodynamic control). In conjugated enones a proton adjacent to the carbonyl group, however, is removed much faster than a y-proton. If the same alkylation, therefore, is carried out in an aprotic solvent, which does not catalyze tautomerizations, and if the temperature is kept low, the steroid is mono- or dimethylated at C-2 in comparable yield (L. Nedelec, 1974). 

A dienol is also formed via hydrogen abstraction by the excited carbonyl group from a second enone molecule in (4.14). This dienol tautomerizes in C6F6 to give the (3,y-unsaturated ketone selectively, the overall reaction thus being deconjugation of the a,(3-unsaturated ketone415K... 

Compound 12 contains a vinylic hydroxyl group and thus is expected to be unstable at higher temperatures in solution. Under the conditions of matrix isolation, however, it is perfectly stable and a third photochemical activation is required to induce the tautomerization to the unsaturated ketone 13. 

We can now proceed. Indoie attacks the unsaturated ketone in Michaei fashion because the conditions are acidic, we protonate the ketone. The product is an enoi, so that is tautomerized to the ketone. This gives the not isoiated intermediate. The next step is ring ciosure, and we have the iminium system of the heterocycie as eiectrophiie. The nucieophiie shouid be distinguishabie as the a-position of the ketone, an enoiate anion equivaient. Under acidic conditions, we cannot have an enoiate anion, so we must empioy the enol. This means a second tautomerization step. Ring ciosure foiiows you may recognize it as equivaient to a Mannich reaction attack of an enoi onto an iminium cation. Loss of a proton and the job is done. 

Reaction of tosylhydrazide with a,(3,y,8-unsaturated ketones, followed by dehydrotoluenesulfonyla-tion affords 3//-1,2-diazepines (Scheme 25) (84JCS(Pl)158l). Tautomeric products (125) and (126) are... 

Upon direct photolysis, the a-(l-hydroxyalkyl)-substituted a, 3-unsaturated ketones 104 gave 1,4-diketones 106 in moderate yields (Scheme 4.47) [71], with the reaction involving an intermolecular 3-hydrogen abstraction. The resultant vinyli-denecydopropanols 105 underwent a formal double tautomerization to afford 106. 

Reaction of tosylhydrazide with -unsaturated ketones, followed by dehydrotoluenesulfonylation affords 3//-l,2-diazepines (Scheme 85) <1984J(P1)1581>. The tautomeric products 170 and 171 are in dynamic equilibrium at room temperature but can be separated by high-pressure liquid chromatography at 6C. 

Conia and coworkers have developed an extensive series of thermal intramolecular ene reactions of unsaturated ketones which occur on extended heating (30 min to several hours) at 300-400 C in pyrex. The initial step of the reaction is reversible tautomerization of the ketone (163) to give enol... 

In this reaction the 2-carbon of the allene is protonated by hydrochloric acid, the resulting carbocation 35 reacting with one molecule of water to give the tetrahedral intermediate 36. This forms the a,(3-unsaturated ketone 23 upon tautomerization, methanol elimination and regeneration of the initial proton in quantitative yield. 

The rearrangement of enynols leads to allene enols, which tautomerize to give a,/ -unsaturated ketones, as shown by the examples 321125 and 351126. 

Note the usefulness of this reaction information of the six-carbon ring. It is also a stereospecific process, but its stereospecificity is not evident in the product, since the proton adjacent to the carbonyl group is lost in the subsequent tautomerization of the 1,2-diketone to form the a-hydroxy-a, 3 unsaturated ketone. 

Conia has developed an intramolecular version of Alder ene reaction of unsaturated ketones, where the carbonyl group functions as the ene component via the tautomerization and the olefinic moiety serves as the enophile This kind of Alder ene reaction is generally known as a Conia reaction. ... 

Irradiation of the a,6-unsaturated ketone 92 produced the dienol 93, which tautomerized to the 6,y-unsaturated ketone 94 (equation 12.69). The notable aspect of this reaction is that it converts a more stable, conjugated enone to a less stable, nonconjugated enone. The reactant, being more conjugated, absorbs UV-vis radiation at longer wavelength than does the product, so the reaction can be driven by radiation that the reactant absorbs but that the product does not absorb efficiently. 

In contrast, tertiary propargylic alcohols with an expellable proton such as 3 will instead proceed via the Rupe rearrangement. Following dehydration to propargylic cation 10, elimination occurs to give enyne 11. Subsequent hychation of the alkyne gives 13, which tautomerizes to the a,P-unsaturated ketone 4. 

Methoxy-3,6-bicyclo[3,2,0]heptadien-7-one is readily available from the photo-chemically induced valence tautomerism and skeletal reorganization of the methyl ether of tropolone. The double bond of the ap-unsaturated ketone can be selectively reduced to give (375). Ozonolysis of (375) in methanol-methylene chloride at low temperature, followed by treatment of the ozonide with liquid sulphur dioxide, gives the substituted cyclopentanone (376X which has been used in yet another prostaglandin synthesis. ... 

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