Enamines structurally characterized

Enamine (Section 17.11) Product of the reaction of a secondary amine and an aldehyde or a ketone. Enamines are characterized by the general structure... 

In 1904, Jocelyn Field Thorpe and co-workers conducted the first studies of the intermolecular dimerization of nitriles. A short time later, the first example of a dinitrile cyclization was described by Moore and Thorpe. Initially, all products of dinitrile cyclization reactions were characterized as imines. However, in 1955, it was determined that the product of the cyclization of adiponitrile was in actuality an enamine. The enamine structure for the product of dinitrile cyclizations has since been confirmed through numerous other studies, and makes sense chemically. The conjugated enamine would be expected to be more stable than the corresponding nonconjugated P-iminonitrile. 

Figure 17.3 Selected examples of structurally characterized enamines.

Elimination unimolecular (El) mechanism (Section 5 17) Mechanism for elimination characterized by the slow for mation of a carbocation intermediate followed by rapid loss of a proton from the carbocation to form the alkene Enamine (Section 17 11) Product of the reaction of a second ary amine and an aldehyde or a ketone Enamines are char actenzed by the general structure... 

An equilibrium has been shown to exist between the enamine-ketimine form of the iminoacyl group (Scheme 4) by the addition of DzO, which effected deuteration of the methyl group, and by the addition of Me02C=CC02Me, which gave 78 (R = C6H4Me-/>). This cyclized product was characterized structurally. The intermediate 79 in this reaction was characterized by H NMR and by additions of HBF4 which formed 80 (409). 

Vinylamine (R1 = R2 = R3 = H) is the simplest primary enamine. It was prepared by gas-phase pyrolysis of ethylamine and characterized by its microwave spectrum which led to a crude determination of its molecular geometry56. The interesting question refers to the extent of planarity or tetrahedral geometry of the amino group and this is discussed in the section on calculations of molecular structures. 

Vilsmeier formylation of 2-benzylisoindole gives the 1-formyl derivative (61%).25 With 1-phenylisoindole reaction occurs at the unsubstituted a-position the intermediate iminium salt on neutralization gives the cross-conjugated enamine system 78, which has been isolated and characterized. X-Ray analysis confirms the assigned structure.95 On hydrolysis, the formyl derivative, which has also been the subject of X-ray crystal analysis (Figs. 4 and 5), is formed. As expected from the analogy with pyrrole chemistry, the aldehyde does not readily form typical carbonyl derivatives. 

Another excellent example from the MacMillan laboratory using enamine-catalyzed key-transformations to accomplish a complex total synthesis was the first total synthesis and structural revision of the cytotoxic marine macrolide callipeltoside C (206) 184). Callipeltosides A-C were isolated and characterized in 1996 and 1997 by Minale et al. They were found to be cytotoxic against the human bronchopulmonary NSCLC-N6 cell line (/C50 values ranging from 11.3 to 30.0 pg/cm ) (185,186). MacMillan s synthesis of 206 takes advantage of three highly selective organocatalytic key transformations to obtain the target in 20 steps and a very... 

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