Synthesis and unexpectedly facile dimerisation of 1-methoxycarbonylpyrrolizin-3-one

Abstract

Flash vacuum pyrolysis of the diethyl esters 2 gives 2-ethynylpyrrole via the anhydride 7; the corresponding dimethyl esters 3 give, under similar conditions, the pyrrolizinone 5, which is remarkably unstable and spontaneously dimerises to give the [2 + 21 cycloadducts 8 and 9 whose structures are proved by X-ray crystallography.

Total Synthesis of Roseophilin

“…However, our initial attempts along these lines revealed that the tricyclic enone 18 formed upon elimination of the sulfone group with t -BuOK in THF at ambient temperature exhibits a peculiar reactivity due to its highly strained character; only a mixture of two dimeric products was formed as suggested by GC/MS analysis of the reaction mixture . We hoped to circumvent this problem by effecting the crucial elimination step in the presence of an appropriate nucleophile, thereby intercepting enone 18 directly upon its formation.…”

C-Vinylpyrroles as Pyrrole Building Blocks

“…74 3-(2-Pyrrolyl)propenoate esters 237 undergo concerted elimination of alcohols under flash vacuum pyrolysis (FVP) conditions to give pyrrolizine-3ones 238, apparently via electrocyclization of the 2-pyrrolylideneketene intermediate 239 (Scheme 86). [75][76][77][78][79][80][81] FVP (700-750 °C, 10 -3 Torr) of 2-(1,2-diethoxycarbonylvinyl)pyrrole (E, Z) (240) affords 2-ethynylpyrrole (241) as the major product together with a small amount of pyrrolizin-3-one 238. Alkyne formation mechanism probably involves E-Z-isomerization of the alkene (if required), accompanied by elimination of ethylene from one (or both) of the ester functions.…”

“…No significant amounts of the parent pyrrolizinone 238 were obtained in either of these reactions, and so it probably formed from 240 by the standard route followed by ester elimination and decarboxylation (Scheme 86). 76 Under analogous conditions, the corresponding dimethyl ester 244 gives the unstable 3-oxo-3Hpyrrolizine-1-carboxylate (245), which further spontaneously dimerizes to afford two isomers of the [2+2]-cycloadduct 246 in a ratio of 2:1. The reaction likely proceeds via the intermediate stabilized diradical 247 (Scheme 88).…”

Synthetic Applications of the Pyrolysis of Meldrum's Acid Derivatives

“…121) has given an alternative approach which has considerably broadened the scope of the pyrolytic route to pyrrolizinones and related compounds. 69,72,73 Scheme 29…”