Synthesis Stork enamine

The total synthesis of the phenolic sesquiterpene (+)-parviflorine was accomplished by L.A. Maldonado and co-workers. The key step in the synthetic sequence was the reaction of an enamine with acrolein to form a bicyclic intermediate, which was subjected to a Grob fragmentation to afford the eight-membered ring of the natural product. The bicyclic ketone substrate was refluxed in benzene using a Dean-Stark trap and the resulting enamine was taken to the next step as crude material. 

An intramolecular variant of the Stork enamine synthesis was utilized during the asymmetric total synthesis of (-)-8-aza-12-oxo-17-desoxoestrone by A.I. Meyers et al.  

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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. " ... 

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. 

Enamines like enolates are alkylated when treated with reactive alkylating agent, a-Substituted enamines can be converted into aldehydes and ketones by acid-catalyzed hydrolysis. Thus, in the three-step process, alkylation of aldehydes and ketones may be carried out via enamines (Stork enamine synthesis) (Scheme 3.19). 

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 enantiose-lective syntheses. The use of A-proline can generate a chiral enamine in situ, thus allowing alkylation to occur, giving alkylated product with good enantioselec-tivity,. The reaction has been done intramolecularly. ... 

Stork enamine synthesis Alkylation of enamines with alkyl halides to afford a-alkylated aldehydes or ketones. 444... 

The reaction of electrophiles with tertiary enamines can be formulated as having several stages and is illustrated by equation 1. The fact that C-substitution can be forced, even when initial reaction occurs at the enamine nitrogen, is one of the synthetic virtues of the Stork enamine synthesis . 

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