Ketone reactivity

With an excess of halocarbonyl reactant or a more reactive ketone like bromoketone, compounds of type 173 may result through reaction of the 2-mercaptothiazole (163a) with the excess of bromoketone (Scheme 88) (156, 199, 270, 291, 292, 519). Thus when Rj = phenyl and = hydrogen, 173 was obtained in 76% yield (292) in aqueous solution and in 20 to 40% in alcoholic solution (292, 519). 

Dimethylamino-l,3-dioxolane/cat. HOAc, CH2CI2, 83% yield. 2-Di-methylamino-l,3-dioxolane protects a reactive ketone under mild conditions it reacts selectively with a C3-keto steroid in the presence of a A -3-keto steroid. C12- and C2o-keto steroids do not react. 

This equation implies that the relative reactivity is independent of the specific nucleophile and that relative reactivity is insensitive to changes in position of the transition state. Table 8.4 lists the B values for some representative ketones. The parameter B indicates relative reactivity on a log scale. Cyclohexanone is seen to be a particularly reactive ketone, being almost as reactive as cyclobutanone and more than 10 times as reactive as acetone. 

A " -3-Ketones do not react with Girard reagents under mild conditions and thus can be separated from other reactive ketones. 

A unique method to generate the pyridine ring employed a transition metal-mediated 6-endo-dig cyclization of A-propargylamine derivative 120. The reaction proceeds in 5-12 h with yields of 22-74%. Gold (HI) salts are required to catalyze the reaction, but copper salts are sufficient with reactive ketones. A proposed reaction mechanism involves activation of the alkyne by transition metal complexation. This lowers the activation energy for the enamine addition to the alkyne that generates 121. The transition metal also behaves as a Lewis acid and facilitates formation of 120 from 118 and 119. Subsequent aromatization of 121 affords pyridine 122. 

With reactive aldehydes an early transition state is probably involved and therefore the steric demands of the aldehyde substituents are not highly influential. On the other hand, with less reactive ketones, the carbon-carbon bond formation is established further along the reaction coordinate, permitting the steric effects to play a greater role in the determination of the transition stale structure. 

The Wittig reagent (56) is best protected as an ester and reacts chemo-selectively with the aldehyde rather than the less reactive ketone in (57),... 

Si. rra(pentafluorophenyl)boron was found to be an efficient, air-stable, and water-tolerant Lewis-acid catalyst for the allylation reaction of allylsilanes with aldehydes.167 Sc(OTf)3-catalyzed allylations of hydrates of a-keto aldehydes, glyoxylates and activated aromatic aldehydes with allyltrimethylsilane in H2O-CH3CN were examined. a-Keto and a-ester homoallylic alcohols and aromatic homoallylic alcohols were obtained in good to excellent yields.168 Allylation reactions of carbonyl compounds such as aldehydes and reactive ketones using allyltrimethoxysilane in aqueous media proceeded smoothly in the presence of 5 mol% of a CdF2-terpyridine complex (Eq. 8.71).169... 

As was found for aldehydes, however, the addition of HOAc led to the alcohol product. For less-reactive ketones, lower yields were found in some cases, and loss of some of the metal hydride occurs through formation of H2 from reaction... 

We now have two possible electrophiles, i.e. one an aldehyde and the other a less reactive ketone. The preferred reaction is thus acetone as enoiate anion nucleophile, with benzaldehyde as preferred... 

Ketones cannot generally be used as acceptors, at least not directly, due to unfavorable equilibrium between the aldol product and the starting ketones. However, highly reactive ketones [87, 88], such as isatin 2 [95] (Fig. 3) and a-keto phosphonates (e.g. 112) [110] can readily be used as acceptors. 

Instead of direct halogenation of ketones, reactions with more reactive ketone derivatives such as silyl enol ethers and enamines have advantages in certain cases. 

The dioxirane epoxidation of a prochrral alkene will produce an epoxide with either one new chirality center for terminal alkenes, or two for internal aUcenes. When an optically active dioxirane is nsed as the oxidant, expectedly, prochiral alkenes should be epoxi-dized asymmetrically. This attractive idea for preparative purposes was initially explored by Curci and coworkers in the very beginning of dioxirane chemistry. The optically active chiral ketones 1 and 2 were employed as the dioxirane precursors, but quite disappointing enantioselectivities were obtained. Subsequently, the glucose-derived ketone 3 was used, but unfortunately, this oxidatively labile dioxirane precursor was quickly consumed without any conversion of the aUcene . After a long pause (11 years) of activity in this challenging area, the Curci group reported work on the much more reactive ketone... 

The desUylation strategy has been used for the cycloaddition of the parent thiocarbonyl yhde la with aldehydes and reactive ketones. The product obtained using A-methyl-3-oxoindolinone as the trapping agent corresponds to the spiro-cyclic compound 125 (168). Thioketene (5)-methylide (127) was reported to react with aromatic aldehydes and some ketones to furnish 2-methylene-substituted 1,3-oxathiolanes (128) (51) (Scheme 5.42). 

A number of ketones have been condensed with ethyl cyanoacetate by this procedure. Reactive ketones such as aliphatic methyl ketones and cyclohexanone condense with ethyl cyanoacetate much more rapidly and give better yields of alkyli-dene esters. It is advantageous with such ketones to use a lower ratio of ammonium acetate-acetic acid catalyst.1... 

The fact that the initial cleavage is reversible has been long suspected from the fact that the quantum yield for Norrish Type I products never approaches one, even for very reactive ketones. Positive evidence for the back reaction was provided by Barltrop, who showed that Type I cleavage of cis-2,3-dimethyl-cyclohexanone is accompanied by its isomerization to hmy-2,3-dimethylcyclo-hexanone.87... 

A very reactive ketone, obtained by Swern oxidation, is condensed in one-pot with MeMgBr. Other oxidation methods lead to the isolation of the ketone hydrate, which fails to react efficiently with Grignard reagents. 

For less reactive ketones where an excess of mercaptan is needed to shift equilibrium (9 b) sufficiently to the right, the measurement of the anodic mercaptan wave is not advantageous, because its height changes only slightly. In the calculation of the equilibrium constant K, the dissociation of the mercaptan according to equilibrium (9 a) must be taken into consideration. 

Since the same compounds are most easily enolised and most electrophilic, they tend to self-condense rather than react with anything else. So that, in the reaction of 2 and 3 under equlibrating conditions, the aldehyde 3 will probably self condense and ignore the less reactive ketone. This chapter looks at ways to overcome that tendency. We examined self-condensation in chapter 19 so we shall look at other cases now. 

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