Stork enamine

G. Stork, Enamine Symposium, 140th National Meeting of the American Chemical Society, Chicago, Sept. 1961. 

Exceptions to this rule may be a result of steric hindrance. However when the Stork enamine method is applied, for example with enamine 10, the less substituted a-carbon becomes connected to the Michael acceptor ... 

The Stork enamine reaction is an important and versatile method for the synthesis of a-substituted aldehydes and ketones. Such products should in principle also be... 

The Stork enamine reaction and the intramolecular aldol reaction can be carried out in sequence to allow the synthesis of cyclohexenones. For example, reaction of the pyrrolidine enamine of cyclohexanone with 3-buten-2-one. followed by enamine hydrolysis and base treatment, yields the product indicated. Write each step, and show the mechanism of each. 

How could you prepare the following cvclohexenones by combining a Stork enamine reaction with an intramolecular aldol condensation (See Problem 23.53.)... 

Sandmeyer reaction, 943 saponification. 809-810 SN1 reaction, 373-375 Sn2 reaction, 363-364 Stork enamine reaction, 897-898 transamination, 1167 Williamson ether synthesis, 655 Wittig reaction, 720-721 Wolff-Kishner reaction, 715-716 Meerwein-Ponndorf-Verley reaction, 746... 

Among other methods for the preparation of alkylated ketones are (1) the Stork enamine reaction (12-18), (2) the acetoacetic ester synthesis (10-104), (3) alkylation of p-keto sulfones or sulfoxides (10-104), (4) acylation of CH3SOCH2 followed by reductive cleavage (10-119), (5) treatment of a-halo ketones with lithium dialkyl-copper reagents (10-94), and (6) treatment of a-halo ketones with trialkylboranes (10-109). 

When enamines are treated with alkyl halides, an alkylation occurs that is analogous to the first step of 12-14. Hydrolysis of the imine salt gives a ketone. Since the enamine is normally formed from a ketone (16-12), the net result is alkylation of the ketone at the a position. The method, known as the Stork enamine reaction is an alternative to the ketone alkylation considered at 10-105. The Stork method has the advantage that it generally leads almost exclusively to monoalkylation of the ketone, while 10-105, when applied to ketones, is difficult to stop with the introduction of just one alkyl group. Alkylation usually takes place on the less substituted side of the original ketone. The most commonly used amines are the cyclic amines piperidine, morpholine, and pyrrolidine. 

When the nitrogen of the substrate contains a chiral R group, both the Stork enamine synthesis and the enamine salt method can be used to perform enantio-selective syntheses. " ... 

Formation of Enamines Investigated in Micro Reactors Organic synthesis 73 [OS 73] Stork enamine formation from cyclohexanone and pyrrolidine... 

OS 73] [R 4a] [P 54] The micro reactor yield (up to 42%) is comparable to that for batch Stork-enamine reactions using p-toluenesulfonic acid in methanol imder Dean and Stark conditions [11],... 

Stork enamine synthesis takes advantage of the fact that an aldehyde or ketone reacts with a secondciry cimine to produce an enamine. Enamines cire resonance stabilized (see Figure 15-25) and have multiple applications. In the first resonance structure, the nitrogen is the nucleophile, while in the second resonance structure, the Ccirbanion is the nucleophile. Some commonly used secondary amines, pyrrolidine, piperidine, and morpholine, are shown in Figure 15-26. 

Some secondary amines commonly used in the Stork enamine synthesis. 

Stork Enamine Synthesis A reaction leading to the formation of an a-alkyl or a-carbonyl compound from an alkyl or aryl halide reacting with an enamine. 

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