Pinacolone enolate ion

For a given aryl moiety, there is a rough correlation between the reduction potential and its reactivity in SRN1 reactions [12]. The order of reduction potential in liquid ammonia, Phi >PhBr >PhNMe3I >PhSPh > PhCl >PhF >PhOPh coincides with the reactivity order determined under photoinitiation. By competition experiments of pairs of halobenzenes toward pinacolone enolate ions under photoinitiation, the span in reactivity from PhF to Phi was found to be about 100,000 [13]. 

When the photoinduced reaction of pinacolone enolate ion with bromobenzene is carried out in DMF as solvent, it leads to the formation of benzene (28%), while in liquid ammonia this byproduct is almost precluded. The reaction in DMSO produces little benzene. On the other hand, THF... 

The photostimulated reactions of vie aminohalo pyridines with acetone or pinacolone enolate ions lead to azaindoles in high yields (75-95%) [67]. When the amino group is protected as pivaloylamino derivative, (as in 17, Sch. 20), the analogs of substitution compounds 18 obtained by the photoinduced reaction of 2-amino-3-iodo-, 3-amino-4-iodo- and 4-amino-3-iodopyridines with acetone or pinacolone enolate ions, afford 5-, 6- and 7-azaindoles in almost quantitative yields by cyclization upon deprotection of the amino group and dehydration under acidic conditions (for example, see Sch. 20) [67]. 

The factors affecting the relative reactivity of aryl halides in SrnI reactions have been analysed and compared645. Competition experiments of pairs of substrates, in photo-stimulated reactions with pinacolone enolate ion in liquid ammonia, reveal a spread of reactivity exceeding three powers of ten. The ease of formation of the radical anion of the substrate appears to dominate the overall reactivity. The rate of dehalogenation of the radical anion may become important when its stability exceeds a certain threshold. When the fragmentation rate of the radical anion intermediate is fairly slow, the overall reactivity diminishes. 

Acetone enolate ion did not react with 66, whereas pinacolone enolate ion reacted to give 18% of 67d145. However, good yields of the substitution product were obtained in the photostimulated reaction of 7-iodonorcarane (68) with acetophenone enolate ion in DM SO (87%). This reaction is inhibited by p-D NB and it is sluggish in the dark (equation... 

Disubstitution product (46%) was the only product obtained in the photostimulated reaction of 70 with pinacolone enolate ion while n-butanethiolate ion led to the monosubstitution product in a relatively low yield (22%) 145. 

The dark reaction of pinacolone enolate ion and Phi in DMSO was described167. The same reaction is stimulated by light and inhibited by radical scavengers. This system was used to study the reactivity of different ketone enolate ions with Phi. In competition experiments, the following reactivity order was determined 2-acetylcyclohexanone (unreactive) < phenylacetone (0.39) < cyclohexanone (0.67) < pinacolone (1.00) < acetone (1.09) < 2-butanone (1.10) < 3-pentanone (1.40)168. 

Carbanions occasionally react with aryl halides spontaneously, mostly under irradiation, or by supplying electrons either from dissolved metals or from a cathode. However, certain Fe+2 salts catalyse the S l reactions with carbanions. That was the case for the reaction of PhBr or Phi with acetone or pinacolone enolate ions in liquid ammonia or DMS0172a, as well as for the reaction of the enolate ion of several carbanions with several aryl and hetaryl halides in DMS0172b. Since these reactions are inhibited byp-DNB andp-cymene, and the relative reactivity of nucleophiles is similar to that determined in photo-stimulated or spontaneous reactions, it seems that FeCl2 initiates the S l process. 

The reaction of carbanions with hetaryl halides has been reported. Thus, pinacolone enolate ion reacts with 2-halothiazoles (127) affording the substitution product 128 in good yields (44-67%) (equation 87)176. 

Ethyl phenylacetate and even the tertiary carbanion methyl diphenylacetate gave 84 and 42%, respectively, of the disubstitution product in their reaction with 2,6-dibromopy-ridine179. However, only monosubstitution product at position 4,134 was obtained in 70% yield in the reaction of 4,7-dichloroquinoline (133) with pinacolone enolate ion (equation 90)179. 

The substitution reaction of o-iodonitrobenzene (135) with pinacolone enolate ion in liquid ammonia has been reported to afford 136 (66%) (equation 91). 

An interesting approach to the synthesis of indoles is the combination of directed orr/w-lithiation followed by an S l reaction324. Thus, the selective or o-lithiation of 2-fluoropyridine (262) by LDA followed by iodination afforded 2-fluoro-3-iodopyridine (263) in high yield (75%). Substitution of the 2-fluorine atom under S Ar conditions is a convenient synthesis of 2-substituted 3-iodopyridines (264) (equation 169), which can react with acetone or pinacolone enolate ions in liquid ammonia, followed by acidic treatment, to give the corresponding substituted 7-azaindoles (265) [R = H, R = Me (75%), R = t-Bu (78%) R = Me, R = f-Bu (70%), R = Me (95%)] (equation 170). 

These iodo(pivaloylamino)pyridines underwent photostimulated S l reaction with acetone or pinacolone enolate ions in liquid ammonia to give, after acidic treatment, the azaindoles 269-271 in good yields324. 

It is interesting to note that the chlorine atom in position 5 did not react under these conditions. Also, 5,7-dichloro-8-/-propoxyquinoline gave only 276 (R = f-Bu) when irradiated with pinacolone enolate ion. However, 5,7-dibromo-8-methoxyquinoline gave the disubstitution product (60%)326. 

The substitution products, formed in the reaction of acetone or pinacolone enolate ions with aromatic substrates bearing a F3C group either ortho or para to the halogen, undergo reactions in which fluoride ions are eliminated. In the case of the ortho-isomer 310, a ring closure product 311 is formed by intramolecular reaction (equation 186)334. 

Recently, evidence for the vinylic nucleophilic substitutions suggests the occurrence of an ionic elimination-addition along with the originally proposed S l route352. Thus, the reaction of /Lbromostyrene with pinacolone enolate ions and FeCl2 as catalyst in DMSO gave a mixture of products 362-366 in yields that depend on the reaction time, 10 min or (3 h). 

Scamehorn, R. G. and Bunnett, J. F., Dark reactions of halobenzenes with pinacolone enolate ion evidence for a thermally induced aromatic Spjjl reaction, /. Org. Chem., 42,1449,1977. 

Transformation of a substrate into its ion radical enhances the species reactivity. Sometimes, this can overcome steric encumbrance of the substituent to be removed. Thus, l,4-di-iodo-2,6-dimethybenzene expels only one, sterically congested, iodine from position 1 upon the action of the tributylstannyl radical. Upon the action of the enolate ion of pinacolone (Me3CCOCH2) in the photoinitiated SrnI process, both iodines (from positions 1 and 4) are substituted (Branchi and co-authors 2000). 

The enolate ions from acyclic and cyclic aliphatic ketones, and mainly those derived from acetone and pinacolone, are the carbanions most extensively studied so far. In general, the substitution products are obtained in good yield under irradiation in both liquid ammonia and dimethylsulfoxide (DMSO). For example, the anti-inflammatory drug fluorobiprophen 1 can be synthesized by the reaction of... 

The anion of nitromethane (31) failed to react with Phi under irradiation in DMSO, as was the case with 1-AdI. However, when the reaction was carried out in the presence of acetone (27a) or pinacolone (27b) enolate ions, l-phenyl-2-nitroethane (161) was formed as major product, together with small amounts of benzene and toluene (equation 104). No products from the coupling with the ketone enolate ions were found169... 

The carbonyl-carbon kinetic isotope effect (KIE) and the substituent effects for the reaction of lithium pinacolone enolate (112) with benzaldehyde (equation 31) were analyzed by Yamataka, Mishima and coworkers ° and the results were compared with those for other lithium reagents such as MeLi, PhLi and AllLi. Ab initio (HF/6-31-I-G ) calculations were carried out to estimate the equilibrium isotope effect (EIE) on the addition to benzaldehyde. In general, a carbonyl addition reaction (equation 32) proceeds by way of either a direct one-step polar nucleophilic attack (PL) or a two-step process involving electron transfer (ET) and a radical ion intermediate. The carbonyl-carbon KIE was of primary nature for the PL or the radical coupling (RC) rate-determining ET mechanism, while it was considered to be less important for the ET rate-determining mechanism. The reaction of 112 with benzaldehyde gave a small positive KIE = 1.019),... 

The solvents and the reaction conditions of choice are usually Hquid ammonia or DMSO and irradiation. The enolate ions of acyclic ahphatic ketones such as acetone, pinacolone, " Z-butanone,"" 3-methyl-2-butanone, > 3-pentanone, - 4-heptanone, and 2,4-dimethyl-3-pentanone > - - react through the Sr I mechanism with aryl and heteroaryl hahdes to afford the a-arylation products under photoinitiation. An example is shown in Eq. (47.6) ... 

If alkenes are used instead of silanes, the intermediate oxocarbenium ion undergoes an acetal -ene reaction. An example is the reaction of acetal 11 with methylenecy-clohexane to give the cyclohexenylmethyl-substituted product 12 (Scheme 8.4) [20]. Silenol ethers are electron-rich alkenes particularly suited for addition to cationic species. Pinacolone-derived enol ether 13, for example, adds to an thioxocarbenium ion generated in situ from S,S-acetal 14 to give thioether 15 (Scheme 8.4) [21]. 

Further examination of the fluoride ion-catalyzed asymmetric aldol reaction of the enol silyl ethers prepared from acetophenones and pinacolone with benzaldehyde using 4b and its pseudoenantiomer 4c revealed the dependence of the stereochemistry of the reactions on the hydroxymethyl-quinudidine fragment of the catalyst (Table 9.3) [10,15]. 

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