Phenyl-substituted monocarboxylic acids

FIGURE 2.9 Mixed linear/cyclic dimers of phenyl-substituted monocarboxylic acids (coupled together through the carboxyl groups and the aromatic 7t-electrons). 

The most strongly pronoimced anti-Langmuir behavior (when comparing the three classes of carboxylic acids) was observed for phenyl-substituted monocarboxylic acids (Figure 2.9). 

Monocyclic piperidine or pyrrolidine alkaloids are also accessible in a Robinson-Schbpf-type condensation if substituted acetone monocarboxylic acids are used as reactive acetone equivalent. For example, the reaction of glutardial-dehyde, methylamine, and two equivalents 3-keto-3-phenyl-propionic acid (194) under slightly acidic conditions (pH=4) afforded ( )-lobelanine (53) in 90% yield (Scheme 11.44). Here, the reaction presumably proceeds via intermediate 195, which is formed in an initial intermolecular Mannich reaction between glutardialdehyde, methylamine, and one equivalent 194. Under the applied reaction conditions, water is eliminated. The formed iminium ion 196 is prone to nucleophilic attack by a second equivalent 194 to furnish the piperidine alkaloid ( )-lobelanine [132,134]. 

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