Nucleophihc addition-elimination reactions

Acyl transfer reactions (Section 17.4) A reaction in which a new acyl compound is formed by a nucleophihc addition-elimination reaction at a carbonyl carbon bearing a leaving group. 

Because of thetr electron deficient nature, fluoroolefms are often nucleophihcally attacked by alcohols and alkoxides Ethers are commonly produced by these addition and addition-elimination reactions The wide availability of alcohols and fliioroolefins has established the generality of the nucleophilic addition reactions The mechanism of the addition reaction is generally believed to proceed by attack at a vinylic carbon to produce an intermediate fluorocarbanion as the rate-determining slow step The intermediate carbanion may react with a proton source to yield the saturated addition product Alternatively, the intermediate carbanion may, by elimination of P-halogen, lead to an unsaturated ether, often an enol or vinylic ether These addition and addition-elimination reactions have been previously reviewed [1, 2] The intermediate carbanions resulting from nucleophilic attack on fluoroolefins have also been trapped in situ with carbon dioxide, carbonates, and esters of fluorinated acids [3, 4, 5] (equations 1 and 2)... 

An alternative possibility in accord with the above labeling results is a nucleophihc addition elimination. The reaction of phenylhthium and vinyl-lithium with S-phenyldibenzothiophenium fluoroborate addresses itself to this problem. 20) This salt reacts with phenyllithium to 5deld 2-phenylthio-o-terphenyl exclusively in nearly quantitative pelds. If an addition elimina-... 

The reactions of carboxyhc acids and their derivatives are summarized here. Many (but not all) of the reactions in this summary are acyl substitution reactions (they are principally the reactions referenced to Sections 17.5 and beyond). As you use this summary, you wiU find it helpful to also review Section 17.4, which presents the general nucleophihc addition-elimination mechanism for acyl substitution. It is instructive to relate aspects of the specific acyl substitution reactions below to this general mechanism. In some cases proton transfer steps are also involved, such as to make a leaving group more suitable by prior protonation or to transfer a proton to a stronger base at some point in a reaction, but in all acyl substitution the essential nucleophilic addition-elimination steps are identifiable. 

The product of this reaction, as its sodium salt, is called a Meisenheimer complex after the German chemist Jacob Meisenheimer, who reported on their formation and reactions in 1902. A Meisenheimer complex corresponds to the product of the nucleophihc addition stage in the addition-elimination mechanism for nucleophihc aromatic substimtion. 

By carefully tuning the structure of the starting materials, Orru et al. [21] developed an efficient synthesis of imidazoline 18 by using essentially the same reaction partners (Scheme 15.8). The key to substrate design is the use of a-aryl-substituted a-isocyanoacetate (17) and the primary amine instead of the secondary amine as reaction partner of the aldehyde. The reaction was initiated by nucleophihc addition of the enolate anion of 17 onto the imine 19, generated in situ. However, the lack of an additional acidic proton a to ester in the Mannich adduct 20 made the P-elimination impossible. On the other hand, the Mannich adduct having a secondary amine remained nucleophilic and could add intramolecularly to the divalent isocyano carbon, leading, after protonation, to the imidazoline 18 in... 

In the first step, acid-catalyzed azomethine formation (113 115) takes place. In the second step, the phosphonium salt 115 is deprotonated to give the P-yhde 116, which (in analogy to an aza-WiTTic reaction) undergoes intramolecular nucleophihc addition to the imine function. The resulting phosphonium betaine 117 eliminates PPh3, thus establishing the indole system 114. 

NaOH SuAror elimination-addition A strong nucleophile used in nucleophihc aromatic substitution reactions as well as elimination-addition reactions. 

The familiar substitution reactions of derivatives of carboxylic acids with basic reagents illustrate nucleophihc substitution at aliphatic sp carbons. (Substitution reactions of carboxylic acids, and their derivatives, with acidic reagents are covered in Chapter 4.) The mechanisms of these reactions involve two steps (1) addition of the nucleophile to the carbonyl group and (2) elimination of some other group attached to that carbon. Common examples include the basic hydrolysis and aminolysis of acid chlorides, anhydrides, esters, and amides. 

Nucleophihc reactions of oxazoles can be characterized by several different outcomes. In many cases nucleophilic addition and elimination of a suitable leaving... 

The elimination-addition mechanism accounts for the substantial difference in the rates of reaction for hydroxide ion compared to amide ion. The reaction with hydroxide ion requires a very high temperature. The reaction with amide ion occurs at the temperature of hquid ammonia. The amide ion is a better nucleophile than hydroxide ion. However, the difference in nucleophihcities cannot explain the very large difference between their rates. The difference between the basicities of the amide ion and hydroxide ion accounts for the different rates. (The pA values of NHj and H2O are 35 and 15.7, respectively.) The rate of the reaction therefore depends on the ehmination step. 

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