Ketones dienolates

The reader is referred to two reviews for numerous examples of intramolecular 7-alkyIations of ketone dienolates. Lansbury et al. have achieved some success in synthesizing 7-alkylated a,3-unsaturated ketones via the use of dienolates of 7-benzenesulfonyl enones and trilithiated derivatives of a -ben-zenesulfonyl enones as nucleophiles. 

Another preparative method for the enone 554 is the reaction of the enol acetate 553 with allyl methyl carbonate using a bimetallic catalyst of Pd and Tin methoxide[354,358]. The enone formation is competitive with the allylation reaction (see Section 2.4.1). MeCN as a solvent and a low Pd to ligand ratio favor enone formation. Two regioisomeric steroidal dienones, 558 and 559, are prepared regioselectively from the respective dienol acetates 556 and 557 formed from the steroidal a, /3-unsaturated ketone 555. Enone formation from both silyl enol ethers and enol acetates proceeds via 7r-allylpalladium enolates as common intermediates. 

For some aromatic ketones the reactive dienols can also undergo electrocycliziidoa to cyclobutenols. ... 

The dienol is unstable, and two separate processes have been identified for ketonization. These are a 1,5-sigmatropic shift of hydrogen leading back to the enone and a base-catalyzed proton transfer which leads to the / ,y-enone. The deconjugated enone is formed because of the kinetic preference for reprotonation of the dienolate at the a carbon. Photochemical deconjugation is a synthetically useful way of effecting isomerization of a,) -unsaturated ketones and esters to the j ,y-isomers. 

The formation of derivatives of this type by free-radical attack has been mentioned previously (see section E above). The most common route to vinylogous halo ketones is by halogenation of dienol acetates or ethers. Both free halogen and A -halo compounds may be employed, and this approach has frequently been used to obtain 6 (axial) halo compounds ... 

Addition of bromine to the dienol acetate (49) gives the 6j5-bromo-A -3-ketone (50). Dehydrobromination of the crude bromo compound in DMF with lithium or calcium carbonate gives the title compound (51). ... 

C—O bonding and Cl—F fission of the intermediate cw-fluoro chlorate (29a), which in turn undergoes oxidation to the fluoro ketone (25) by a concerted elimination of chlorous acid. A similar transition state (30) approximating an allylic carbonium ion could be involved in the reaction of the dienol derivatives (6) with perchloryl fluoride, which would be expected to give rise to the c/5-adduct (30a). Reaction of the latter with water leads to product and chlorate ion. 

Bertrand and Santelli (89) have investigated the hydrolysis, under apparently heterogeneous conditions, of 4,5-hexadien-2-yl tosylate, 114, and 4-methyl4,5-hexadien-2-yl tosylate, 115. After 90 min at 80°, 114 upon steam distillation yields a mixture consisting of 3% hydrocarbon 67% of cis- and rrans-2-methylcyclopropyl methyl ketone, 116 and 30% of 4,5-hexadien-2-ol, 117. When optically active 114 was treated under similar conditions, the resulting rrans-2-methylcyclopropyl methyl ketone had an inverted configuration at the reaction center, whereas the dienol 117 was found to be racemic (90). This... 

Scheme 1.8 shows some intramolecular enolate alkylations. The reactions in Section A involve alkylation of ketone enolates. Entry 1 is a case of a-alkylation of a conjugated dienolate. In this case, the a-alkylation is also favored by ring strain effects because y-alkylation would lead to a four-membered ring. The intramolecular alkylation in Entry 2 was used in the synthesis of the terpene seychellene. 

The irradiation of ortho tolyl ketones affords dienols 413) via an analogous intramolecular H-abstraction. The dienols formed usually tautomerize back to starting material, but they can also be trapped by dienophiles in inter-414a) (4.12) and intramolecular414b) (4.13) Diels-Alder reactions. This latter... 

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... 

A simple two-step protocol for the generation of a terminal diene is to add allyl magnesium bromide to an aldehyde or a ketone and subsequent acid or base catalysed dehydration (equation 34)72. Cheng and coworkers used this sequence for the synthesis of some indole natural products (equation 35)72a. Regiospecific dienones can be prepared by 1,2-addition of vinyllithium to a,/l-unsaturated carbonyl compounds and oxidative rearrangement of the resulting dienols with pyridinium dichromate (equation 36)73. 

A difference in the reactivities and selectivities between tetra-n-butylammonium borohydride and sodium borohydride in the reduction of conjugated ketones is well illustrated with A1-9 2-octalone (Scheme 11.3) [17], Reduction with the sodium salt in tetrahydrofuran is relatively slow and produces the allylic alcohol (1) and the saturated alcohol (2) in a 1.2 1 ratio whereas, in contrast, tetra-n-butylammonium borohydride produces the non-conjugated alcohol (3) (50%) and the saturated alcohol (2) (47%), with minor amounts of the ketone (4), and the allylic alcohol (1) [16]. It has been proposed that (3) results from an initial unprecedented formation of a dienolate anion and its subsequent reduction. 

Dehennin L, Scholler R. 1973. Dienol heptafiuorobutyrates as derivatives for gas liquid chromatography of steroidal A -3-ketones determination of the structure of the isomeric dienol esters. Tetrahedron 29 1591-1594. 

This enzymic conversion involves two enzymes, a dehydrogenase and an isomerase. The dehydrogenase component oxidizes the hydroxyl group on pregnenolone to a ketone, and requires the oxidizing agent cofactor NAD+ (see Box 11.2). The isomerase then carries out two tautomerism reactions, enolization to a dienol followed by production of the more stable conjugated ketone. 

Enolates may be derived from a,/l-unsaturated ketones 16 by base-catalyzed proton abstraction. Under kinetic control the a -proton is abstracted and a cross-conjugated metal dienolate is formed, whereas under thermodynamic conditions the extended dienolate is the major product3,, l. Successful alkylations of dienolates derived from cyclic a,/l-unsaturated ketones have been performed (see Section 1.1.1.3.1.1.2.1.). The related a,/ -unsaturated ester systems have also been investigated22-24. Open-chain structures 16 pose a rather complicated... 

Examples of alkylations of dienolates derived from a,/J-unsaturated ketones by base-catalyzed proton abstraction38 38" are shown for enolate 32. Here it is also evident that the presence of a 1,3-interaction greatly influences the diastereoselectivity. 

A further example stressing the effect on regiochemistry exerted by the presence of a methyl group on the dienolate moiety is given by ketone 199 in the reaction with pure... 

The reaction of potassium dienoxy borates with A-fluorobis(phenylsulfonyl)amine (la) gives y-fluoro enones in good yield. The potassium dienoxy borates are prepared by treating potassium enolates derived from unsaturated ketones with 2-phenyl-1,3,2-benzodioxaborole. This methodology offers a convenient alternative to the traditional fluorination of dienol acetates, ethers, or enamines.145 An example is given by the formation of 13.145... 

Cleavage of enol and dienol methyl ethersTreatment of these, substrates in aqueous acetonitrile at 20° for 5 minutes gives the aldehydes or ketones in quantitative yield after aqueous worje-up or treatment with alumina. 

The conjugate addition of unstabilized enolates to various acceptors was conceptually recognized by early researchers however, complications were encountered depending on the enolates and acceptors employed. Reexamination of this strategy was made possible by the development of techniques for kinetic enolate formation. This discussion is divided into three enolate classes (a) aldehyde and ketone enolates, azaenolates or equivalents, (b) ester and amide enolates, dithioenolates and dienolates and (c) a,0-carboxylic dianions and a-nitrile anions, in order to emphasize the differential reactivity of various enolates with various acceptors."7 The a-nitrile anions are included because of their equivalence to the hypothetical a-carboxylic acid anion. 

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