An efficient route to the pyrrolizidine ring system via an N-acyl anion cyclisation process

Facile Synthesis of Diastereoisomerically and Optically Pure 2-Substituted Hexahydro-1H-pyrrolizin-3-ones

“…Only a few examples of diastereoisomerically pure 2,5-disubstituted derivatives have been reported in the literature [4]. A larger number of 2-substituted pyrrolizidinones have been prepared [5], although often as inseparable mixtures of diastereoisomers [6 ± 11]. Here, we describe a versatile new synthesis of diastereoisomerically and optically pure 2-substituted pyrrolizidinones starting from l-proline.…”

“…Treatment of (À)-2 with LDA (for abbreviations, see Scheme captions), followed by addition of bromide 3, afforded diastereoisomers (À)-4 and (À)-5 in a disappointingly low total yield of 27%, which could not be increased upon variation of the reaction conditions (Scheme 2). Analogous alkylations with more-potent electrophiles, such as MeI [5], PhCH 2 Br, and allyl bromide [13], or aldehydes [7], had previously given good results. But to install our functionalized substituents in reasonable yield, another strategy would be required.…”

“…Results and Discussion. ± In analogy to the synthesis of 2-methyl derivatives described in the literature [5], we envisioned preparing compound (À)-1 by alkylation Scheme 1. Synthesis of 2-Mono-and 2,5-Disubstituted Hexahydro-1H-pyrrolizin-3-ones Starting from l-Proline Helvetica Chimica Acta ± Vol.…”

Short Syntheses of (-)-( R )-Pyrrolam A and (1S)-1-Hydroxyindolizidin-3-one

“…2 As distinguished from the more common and structurally more complex necine bases, the pyrrolams exhibit only moderate biological activity. In the wake of this paper, several total syntheses of pyrrolam A (1) ( Figure 1) were reported, e.g., by the groups of Ohta, 3 Murray, 4 Palmisano, 5 Huang, 6 and Snyder. 7 We now contribute another, short one, based upon the generation of the 1-azabicyclo [3.3.0]oct-3-en-2-one moiety of 1 from benzyl prolinate (2) in one step.…”

Synthesis of Polysubstituted Pyrrolizidines from Proline Derivatives and Conjugated Nitroolefins

“…Murray et al. [3] recently reported on the enantioselective ring closure of an N,N-disubstituted N-acetylprolinamide via its N-acyl anion. A stereocontrolled synthesis has been proposed by Pilli and Russowski [4] by using the addition of a chiral boron enolate to cyclic N-acyliminium ions.…”