Enamines, formation

There have been a number of refinements to the procedure, both in the enamine formation and in the reduction. Furthermore, the procedure can be adapted to 2-substituted indoles by introducing an acyl substituent on the enamine intermediate. 

The original flask used for the enamine formation can be used after the attachment of a Y-shape tube fitted with a dropping funnel and a reflux condenser protected with a tube packed with a drying agent such as anhydrous calcium chloride. 

The presence of 1,3-diaxial interaction between the C-2 alkyl group and the C-4 axial hydrogen atom is reflected in the rate of enamine formation of 2-substituted cyclohexanone. It has been shown by Hunig and Salzwedel (20) that even under forcing conditions, the yield of pyrrolidine and morpholine enamines of 2-methylcyclohexanone does not exceed 58%, whereas the C-2 unsubstituted ketones underwent enamine formation under rather milder conditions in better than 80 % yield. 

C. Secondary Reactions in Enamine Formation from Ketones and Amines. ... 

The primary objectives of this chapter are to detail the methods by which enamines (a,/3-unsaturated amines) (I) can be synthesized and the mechanisms of enamine formation. The enamines discussed are those in which the nitrogen is tertiary and, with the exception of a few selected examples, Contain no other functional groups. The term simple enamines might be used to describe the majority of enamines noted in this chapter. 

This innovation was exploited by Stork and his co-workers (6-8) for a study of enamine formation from a variety of ketones and secondary amines. 

C. Other Methods of Enamine Formation O. Additional Examples of Enamine Formation... 

While enamines can usually be obtained directly from ketones and secondary amines their formation by an indirect route may bo advantageous. The previously mentioned condensation of rnethyl ketones during azeotropic enamine formation has prompted the alklyation (J) or acylation and reduction (59) of Schiff s bases. A parallel method uses the formation and desulfurization of N-acylthiazolines followed by hydride reduetion (60,61). 

An enamine was obtained in the synthesis of coronaridine (648) by aluminum hydride reduction of a bridged lactam, followed by dehydration on alumina. Additional examples of enamine formation by reduction of enamides (649) and thioenamides (650) were reported. 

The long known catalyses of some ketone condensation reactions by secondary amines, can be postulated to have their basis in the reactions of enamine intermediates with ketones. The unsuitability of methyl ketones for azeotropic enamine formation is based on this phenomenon. Recent studies in cyclization reactions have added further support to this concept (354). 

S Conditions for enamine formation and various acids used in the... 

We have previously discussed that keto-aldehydes react with anilines first at the aldehyde carbon to form the aldimine. Subsequent condensation with another aniline formed a bis-imine or enamino-imine. The aniline of the ketimine normally cyclizes on the aldimine (24 —> 26). Conversely, cyclization of the aldimine could be forced with minimal aniline migration to the ketimine using PPA (30 —> 31). The use of unsymmetrical ketones has not been thoroughly explored a few examples are cited below. One-pot enamine formation and cyclization occurred when aniline 48 was reacted with dione 49 in the presence of catalytic p-TsOH and heat. Imine formation occurred at the less-hindered ketone, and cyclization with attack on the reactive carbonyl was preferred. ... 

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