Reactions involving alkyl-oxygen bond formation

1 Reactions involving alkyl-oxygen bond formation 

The reverse of the Aal1 cleavage of an ester is the reaction of a neutral carboxylic acid with a carbonium ion, viz. 

Only carbonium ions and alkylating agents of similar high reactivity, such as trialkyloxonium cations133, will attack the very weakly nucleophilic carboxylic acid group at a useful rate under normal conditions. Ester formation by alkylation of the carboxyl oxygen atom normally involves the carboxylate anion, viz. 

This is formally the reverse of the BA1,1 cleavage of an ester, and is the only one-stage mechanism for ester formation available for the ionized carboxyl group. Numerous methods are, of course, available which involve initial electrophilic attack on the carboxylate group, followed by a displacement at the carbonyl carbon atom of the intermediate formed, which is often an anhydride. An example134 is the esterification of carboxylic acids in the presence ofp-toluenesulphonyl chloride in pyridine, viz- 

Simple alkylations of carboxylate anions, by such alkylating agents as alkyl halides, dialkyl sulphates, and quaternary ammonium compounds, are generally straightforward SN2 reactions, and will not be discussed here. 

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The possibility of the enolate anion acting as if its charge were effectively concentrated on carbon or on oxygen was discussed previously in connection with aldol addition (Section 17-3B). However, the situation there was quite different from the one here, because aldol addition is easily reversible, whereas alkylation is not. Furthermore, while the aldol reaction involving C-O bond formation is unfavorable (AH° = + 20 kcal mole-1) compared to C-C bond formation (AHn = —4 kcal mole-1), both O- and C-alkylation of the anion have AH° < 0 (see Exercise 17-64). 

From the recent advances the heteroatom-carbon bond formation should be mentioned. As for the other reactions in Chapter 13 the amount of literature produced in less than a decade is overwhelming. Widespread attention has been paid to the formation of carbon-to-nitrogen bonds, carbon-to-oxygen bonds, and carbon-to-sulfur bonds [29], The thermodynamic driving force is smaller in this instance, but excellent conversions have been achieved. Classically, the introduction of amines in aromatics involves nitration, reduction, and alkylation. Nitration can be dangerous and is not environmentally friendly. Phenols are produced via sulfonation and reaction of the sulfonates with alkali hydroxide, or via oxidation of cumene, with acetone as the byproduct. 

The first, and fundamental, piece of evidence necessary for a discussion of the detailed mechanism of any chemical change is the identification of the covalent bonds formed and broken this may or may not be the same thing as the identification of the products of the reaction. In the case of ester hydrolysis or formation the alternatives involve the cleavage or formation of bonds from oxygen to the carbon atom of either an alkyl or an acyl group, and it is in principle, and generally also in practice, a simple matter to distinguish between these alternatives. 

Catalytic C-C bond formation via sp- C-H bond cleavage represents the ultimate reaction in organic synthesis. A relatively ideal catalytic reaction system involves the use of sp3 C-H bonds adjacent to a heteroatom such as nitrogen and oxygen atoms. Recently, Jim et al. [69] succeeded in the Ru3(CO)12-catalyzed alkylation of an sp3 C-H bond a to the nitrogen atom in benzyl-(3-methyl-2-pyridinyl)amine by means of chelation assistance (Eq. 43). In this case, the coordination of the pyridine nitrogen to the ruthenium complex followed by C-H... 

Disilylalkyllithiums. A reaction scheme for C-C bond formation that involves umpolung of an oxygenated carbon atom may exploit a gem-disilyl compound as starting material, although its availability is the primary consideration. Alkylation and oxidation protocols are routine. 

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