Piperideine aldol reactions

Isotripiperideine and a-tripiperideine structures differ from each other in a new C—C bond formed in is otripiperideine by an aldol reaction (296, 297). In aqueous media at pH 2-13, two molecules of -piperideine yield tetrahydroanabasine (297). 

The last isomer, the so-called aldotripiperideine (185), is obtained by the action of acid catalysts on a-tripiperideine at its boiling point (298,299), or in aqueous solution at pH 9.2 and 100°C. Further aldol reaction between tetrahydroanabasine and A -piperideine obviously occurs. Hydrogenolysis of this compound gives dihydroaldotripiperideine (186) which is convertible into matridine (187), a reduction product of the alkaloid matrine. 

The dimer of 1-methyl- -pyrroline (39) was obtained by reduction of N-methylpyrrole with zinc and hydrochloric acid (132) and, together with the trimer, by mercuric acetate dehydrogenation of N-methylpyrrolidine (131). J -Pyrroline-N-oxides form dimers in a similar manner (302). Treatment of 1,2-dimethyl-zl -piperideine with formaldehyde, producing l-methyl-3-acetylpiperidine (603), serves as an example of a mixed aldol reaction (Scheme 18). 

As predicted, l,2,3,4-13C-labeled acetone dicarboxylate (15) provided an intact three-carbon chain into lycopodine. It also helped to explain why two molecules of pelletierine (12) were not incorporated (Scheme 6.3) [12]. As before, lysine (6) is converted to piperideine (8) via a decarboxylation. Then a Mannich reaction of labeled 15 with 8 provides pelletierine 12. The other half of the molecule to be incorporated must be pelletierine-like (12-CC>2Na), still containing one of the carboxylates. An aldol reaction of the two pelletierine fragments and a series of transformations leads to phlegmarine 9. Oxidation of 9 involving imine formation between N-C5, isomerization to the enamine and then cyclization onto an imine (at N-C13), provides lycopodine 10. Phlegmarine 9 and lycopodine 10 are proposed as... 

Condensation of A pyrroline with pyrrole readily affords a stable compound, 2-(2-pyrrolidyl)pyrrole.97 The pyrrole trimer345> 848 and indole dimer347 are formed by analogous aldol reactions. The dimerizations of some derivatives and analogs of J1-pyrroline and Zl -piperideine, e.g. J1-pyrroline-2-carboxylic acid and 4-thia-J1-piperideine-2-carboxylic acid, take a similar course.348... 

Curiously, neither J -piperideine nor tetrahydroanabasine undergo aldolization in strongly acidic or strongly alkaline media the reaction occurs only at pH 2-13, when both the free base and its salt are present (295). This relation between the rate of aldolization and pH indicates that aldolization occurs by condensation of the methylene group of the immonium salt with the free base. 

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