Prolines enaminone

The activation of carbonyl compounds via enamine intermediates is an important part of organocatalysis. List and coworkers analyzed crystal structures of several proline enaminones and compared them with density functional theory-calculated structures of the ground and transition states. ... 

The most convincing evidence on the existence of a proline enamine came in late 2010 from List s group, who elucidated the structure of both aldehyde and ketone-derived proline enaminones (7 and 8 in Figure 17.3) using X-ray crystallography. The enamines were found to remain in an ( )-configuration around the double bond, which maintains an exclusive anti-conformation with respect to the carboxylic acid group [15]. 

Condensation of cyclohexanone with ethyl prolinate 199 under Dean-Stark conditions gave the enaminone 200, which was reduced in three stages to pyrrolizidine 201, Scheme 53 (76CJC1512 78CJC320). 

FIGURE 2.13. Proline-derived enaminones prepared by List. 

Similar peptide dendrons from the 2.2.2.2 series prepared in a library format were screened, while still on the beads, for potential aldolase activity.Probes forming colored enaminones or releasing fluorescent fragments via enolization or retro-aldol reactions were used for the screening. Lysine- and proline-rich sequences were identified with the enaminone-forming and enolization-sensitive probes. 

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