Pyrrolizidine 3.5- dioxo

A number of syntheses of pyrrolizidine derivatives are based on cyclization of amino acids such as /3-(pyrrolidin-2-yl)propionic acid, 4-aminopimelic acid, and their homologues to give 3-oxo- and 3,5-dioxo-pyrrolizidines. Reduction of these cyclic amides leads to pyrrolizidines. 

Sorm and Beranek39 used an intramolecular acylation in their synthesis of l-azoniumtricyclo[3.3.3.0]undecane (66). Condensation of nitromethane with acrylonitrile in the presence of an alkaline catalyst resulted in the formation of tris-(2-cyanoethyl)nitromethane (60), which afforded the triethyl ester 61 on hydrolysis followed by esterification. The ester was reduced catalytically to give a pyrrolidone (62). The derivative (62) gave rise to 8-(j8-carboethoxyethyl)-3,5-dioxo-pyrrolizidine (63) on heating. Reduction of 63 resulted in the formation of 8-(y-hydroxypropyl)pyrrolizidine (64). Replacement of the hydroxy group by bromine (65), followed by cyclization, afforded the tricyclic compound 66. 

Oxo- and 3,5-dioxo-pyrrolizidines can be regarded as mono- and di-lactams, respectively, and hence exhibit typical amide properties. They are readily reduced to amines electrochemically (see, e.g. refs. 29 and 31) or with lithium aluminum hydride (see, e.g., refs. 30 and 33). 

Hydrogenation of nitropimelates under drastic conditions has been widely used for the construction of simple alkyl-substituted pyrrolizidines. Colonge and PouchoP have developed a milder route to 3,5-dioxopyrrolizidines starting from 4-nitropimelate esters [Eq. (10)]. Raney nickel reduction of the nitroester gave a pyrrolidone that afforded the 3,5-dioxo compound (18) on distillation. 

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