Enamines 1-Enamino carbonyl

An interesting application to the synthesis of a-diketones, a-ketoesters and a-ketoa-mides, starting from ketones, esters and amides, was achieved by Wasserman and Ives . The method involves conversion of the starting carbonyl compound to the corresponding enamino carbonyl compound, followed by oxidative cleavage of the enamine double bond by singlet oxygen (Scheme 7). 

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. ... 

A Piperidine acts both as a nucleophile and as a base. First it combines with the pyrylium cation at C-2, forming an adduct which then ring opens, deprolonates and tautomerizes to an enamino ketone (Schema 4.3), This product cyclizes through an intramolecular reaction between the enamine unit and the carbonyl group, followed by dehydration to form the phenylpiperidine. 

The alkylation of caclohexanone has been studied as a model reaction in detail. Generally, enamino compounds (126) are allowed to react with alkyl halides or a, 3-unsaturated carbonyl compounds. The enamine (126a) is prepared directly from the ketone and a chiral secondary amine (route A). A metalloenamine (126b) can be synthesized from chiral azomethine, derived from the model ketone and a primary chiral amine (route B). The primary amine used for the formation of (126b) must possess an oxygen function. This oxygen function plays a key role in the coordination of the lithium ion in the complex (126b). 

Another synthetically useful carbon bond-forming reaction involves reaction of diiron nonacarbonyl with halo-carbonyl compounds. Noyori found that a,a -dibromoketones (498) react with diiron nonacarbonyl [Fe2(CO)9] to give an iron stabilized alkoxy zwitterion (499). The intermediate Jt-allyl iron species reacts with alkenes in a stepwise manner (initially producing 500) to give cyclic ketones such as 501, 23 and the product is equivalent to the product of a [3-t2]-cycloaddition with an alkene (sec. 11.11). This cyclization method is now known as Noyori annulation. This reaction is related to the Nazarov cyclization previously discussed in Section 12.3.C. Enamines can react with 498, but the initially formed enamino ketone product eliminates the amino group to form cyclopentanone derivatives. Intermediates such as 499 may actually exist as cations hound to a metal rather than as the alkoxide-iron structures shown.323b-d noted that Zn/B(OEt)3 is... 

The reaction of P-keto acid derivatives and ammonia or amines relies on initial reaction with an aldehyde or ketone moiety. The carbonyl must be P- to the carboxyl group, however, in order to obtain the enamino acid or enamino-ester derivative (an enamine is a "vinyl amine," first used synthetically by Stork, and they are well known). These enamino derivatives are actually 3-aminopropenoic... 

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