Nucleophilic substitution carboxylic acid derivatives

Nucleophilic Substitution Carboxylic acid derivatives Alkyl halides... 

Chemoselective SN reactions of nucleophiles with carboxylic acid derivatives are guaranteed to take place without the risk of an overreaction when the substitution mechanism of Figure 6.4 applies. This is because as long as the nucleophile is present, only one reaction step is possible the formation of the negatively charged tetrahedral intermediate. Figure 6.40 summarizes this addition in the top line as Reaction 1 (— B). 

Oxidative carbonylation of alkenes is a unique reaction of Pd(II). Three types of oxidative carbonylation to give -substituted acid derivatives 130, a, -unsaturated esters 132 and succinate derivatives 134 are known, which can be understood by the following mechanism. Palladation of alkenes with PdX2, followed by CO insertion, generates the acylpalladium intermediate 129 whose reductive elimination affords -substituted carboxylic acid derivatives 130 (path a). Reaction in alcohol in the presence of a base starts by the formation of the alkoxycarbonylpalladium 128. Carbopalladation of alkene with 128 generates 131. Then y3-H elimination of the intermediate 131 yields the a-unsaturated ester 132 (path b). Further CO insertion to 131 gives the acylpalladium intermediate 133 and its alcoholysis yields the succinate derivative 134 (path c). Formation of the jS-alkoxy ester 130 (X-OR) is regarded as nucleophilic substitution of Pd-X in 131 with alcohols. 

Extensive studies have been carried out on nucleophilic substitution of a-halocarboxylic acid derivatives containing a chiral auxiliary in the carboxylic moiety. Racemisation of the labile chiral centre in the a-position to the carbonyl—induced by additives such as polar solvents, bases or halide salts—allows a high asymmetric induction through a DKR process to be obtained. This methodology has been recently recognised as a powerful synthetic method for asymmetric syntheses of a-heteroatom-substituted carboxylic acid derivatives. 

CARBOXYLIC ACID DERIVATIVES NUCLEOPHILIC ACYL SUBSTITUTION... 

Carboxylic Acid Derivatives Nucleophilic Acyl Substitution... 

Both stages involve more than one step and these steps differ in detail among the various carboxylic acid derivatives and for different reaction conditions This chapter is organized to place the various nucleophilic acyl substitutions into a common mechanis tic framework and to point out the ways m which individual classes differ from the rest... 

Conversions of acid anhydrides to other carboxylic acid derivatives are illustrated m Table 20 2 Because a more highly stabilized carbonyl group must result m order for nucleophilic acyl substitution to be effective acid anhydrides are readily converted to carboxylic acids esters and amides but not to acyl chlorides... 

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