Ketones electrophilic reactions

The stmcture of the ketones produced from unsymmetrical internal perfluoroepoxides has been reported (5). The epoxide ring may also be opened by strong protic acids such as fluorosulfonic acid or hydrogen fluoride at elevated temperatures (23—25). The ring opening of HFPO by sulfur trioxide at 150°C has been interpreted as an example of an electrophilic reaction (26) (eq. 3). 

In contrast, fluorinated ketones have been used as both nucleophilic and electrophilic reaction constituents The (Z)-lithium enolate of 1 fluoro 3,3-di-methylbutanone can be selectively prepared and undergoes highly diastereoselec-tive aldol condensations with aldehydes [7] (equation 8) (Table 4)... 

There is no simple answer to this question, but the exact experimental conditions usually have much to do with the result. Alpha-substitution reactions require a full equivalent of strong base and are normally carried out so that the carbonyl compound is rapidly and completely converted into its enolate ion at a low temperature. An electrophile is then added rapidly to ensure that the reactive enolate ion is quenched quickly. In a ketone alkylation reaction, for instance, we might use 1 equivalent of lithium diisopropylamide (LDA) in lelrahydrofuran solution at -78 °C. Rapid and complete generation of the ketone enolate ion would occur, and no unreacled ketone would be left so that no condensation reaction could take place. We would then immediately add an alkyl halide to complete the alkylation reaction. 

The nucleophile adds to the e,/3-unsaturated ketone electrophile in a Michael reaction to generate a new enolate as product. 

The previous sections dealt with reactions in which the new carbon-carbon bond is formed by addition of the nucleophile to a carbonyl group. Another important method for alkylation of carbon nucleophiles involves addition to an electrophilic multiple bond. The electrophilic reaction partner is typically an a,(3-unsaturated ketone, aldehyde, or ester, but other electron-withdrawing substituents such as nitro, cyano, or sulfonyl also activate carbon-carbon double and triple bonds to nucleophilic attack. The reaction is called conjugate addition or the Michael reaction. 

Among the electrophilic reaction parmers of the enamine nucleophiles, aldehydes and ketones are arguably the most important class. The addidon of an enamine to a carbonyl compound affords aldol products after hydrolysis (Scheme 13). In this process, one or two new stereogenic centers and one carbon-carbon bond are formed. 

The use of mediators to improve reactivity or selectivity in nitrone cycloaddition chemistry begins with the nitrone generation step. As is well known, the N-alkyla-tion of oximes provides one of the most direct and convenient synthetic routes to N-alkylated nitrones from readily available aldehydes and ketones. Electrophilic mediators have been employed to activate alkenes for N-alkylation, both in intramolecular and intermolecular reactions. They include activation of the internal alkene function by the action of (a) strong nonmetallic electrophiles such as phenyl-selenenyl sulfate (159), and (b) metallic catalysts such as Ag(I) (160) and Pd(II) ions... 

The C=C bond in a 5-(alkylidene)oxazoline 644 is activated for electrophilic reactions similar to that in analogous vinyl acetates. Rohm Haas researchers exploited this property to prepare chloromethyl ketone fungicides 646 (Scheme 8.203). The overall process constitutes an indirect chlorination of a-amido ketones since the 5-(vinylidene)oxazolines were prepared from a-amido ketones. 

Addition reactions occur in compounds having n electrons in carbon-carbon double (alkenes) or triple bonds (alkynes) or carbon-oxygen double bonds (aldehydes and ketones). Addition reactions are of two types electrophilic addition to alkenes and alkynes, and nucleophilic addition to aldehydes and ketones. In an addition reaction, the product contains all of the elements of the two reacting species. 

The chemistry of cyclopropanol [7] has long been studied in the context of electrophilic reactions, and these investigations have resulted in the preparation of some 3-mercurio ketones. As such mercury compounds are quite unreactive, they have failed to attract great interest in homoenolate chemistry. Only recent studies to exploit siloxycyclopropanes as precursors to homoenolates have led to the use of 3-mercurio ketones for the transition metal-catalyzed formation of new carbon-carbon bonds [8] (vide infra). 

The electrocarboxylation of aldehydes and ketones leads to the corresponding a-hydroxycarboxylic acids that can easily be converted into carboxylic acids via a hydrogenation reaction [7]. It has been reported that the electrocarboxylation of aromatic ketones occurs through the reaction of C02 onto the activated carbon atom of the carbonyl group of the ketyl radical anion generated upon electron transfer to the ketone [7]. Otherwise, the aforementioned intermediate is likely to be a resonance hybrid (see Equation 12.23), and its electrophilic reaction with C02 may take place both at the carbon or the oxygen atom [42, 43]. 

Ketone dilithio a,ft-dianion species (74) have been generated by the tin-lithium exchange reaction of the lithium enolate of /3-tributyltin-substituted ketones.291 Reaction with carbon electrophiles gives substituted ketones. 

Exercises 15 and 17 show that rule 2 should be applied cautiously in nucleophilic reactions of unsaturated ketones. This is true also for electrophilic reactions for example, osmium tetraoxide selectively oxidizes 40 at the isolated double bond (yield -90%),52 despite the fact that its HOMO is lower in energy. 

While aliphatic aldehydes fail to react cleanly, the reaction of 21 with benzaldehyde in the presence of 1 equiv of TBSOTf gives the TBS-sub-stituted aldol adduct 49 as a 1 1 ratio of diastereomers. In addition to aldehydes and ketones, electrophilic additions can also be achieved with acetals (Figure 11). The reaction of 21 with acetaldehyde diethyl acetal promoted by TBSOTf gives 3//-pyrrolium complex 50 as a 1 1 ratio of diastereomers, a reaction that circumvents the poor results obtained with aliphatic aldehydes. 

Fig. 12.10. Mechanism of the a-oxygenation of ketones in reactions with selenium dioxide an electrophilic substitution reaction (—> —> C) is followed by a /(-elimination at the C-0 single bond.

Zirconium-benzyne complexes have been used rather extensively in organic synthesis.8 45 For this purpose, one particularly important characteristic of zirconium-aryne complexes is that olefin insertion into the Zr—C bond occurs stereospecifically. Thus, when generated in situ, the zirconium-benzyne complex (45) reacts with cyclic alkenes to give exclusively the cis-zirconaindanes (46), which upon treatment with electrophiles provide access to a variety of m-difunctionalized cycloalkanes (47-49) (Scheme 5).46 For example, carbonylation of intermediate 46 affords tricyclic ketone 49, reaction with sulfur dichloride gives thiophene 48, and reaction of 46 with tert-butylisocyanide followed by I2 gives 47 via 50 and, presumably, intermediate 51 [Eq. (12)]. 

A key reaction in the formation of alkaloids involves the formation of C-N bonds between amines and aldehydes or ketones. The reaction involves nucleophilic addition followed by the elimination of water to give an imine or Schiff base. The protonated form of this imine is believed to act as an electrophile in a Mannich... 

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