The Synthesis of 1,(7)-Substituted Pyrrolizidin-3-ones

Stereoselective synthesis of novel tetrahydroxypyrrolizidines

“…Several types of processes, for example, radical and ionic cyclizations, carbene insertions and acylimmnium cyclizations have been reviewed. 4 Other procedures such as Claisen-like intramolecular acylation involving a-pyrrolidinyl sulfones, 5 ring-closing metathesis of disubstituted ethenyl pyrrolidines, 6 or intramolecular titanium-mediated coupling reactions of a-substituted succinimides 7 have been described. Other processes include the cis-allylation of a chiral lactam skeleton derived from D D -malic acid, 8 cyclizations of acetylenic sulfones with b-chloroamines, 9 cyclizations of N-propargylaminyl radicals 10 and cycloaddition processes including tandem inter[4+2]/inter[3+2], 11 hetero DielsAlder reactions, 12 and [2+2], 13 and 1,3-dipolar cycloadditions.…”

Tandem Double‐Michael‐Addition/Cyclization/Acyl Migration of 1,4‐Dien‐3‐ones and Ethyl Isocyanoacetate: Stereoselective Synthesis of Pyrrolizidines

“…[1,2] The formation of the pyrrolizidine framework generally involves building a second five-membered ring onto a preformed pyrrolidine moiety. [1][2][3] Therefore, the development of a new strategy for the efficient construction of the azabicyclic skeleton from simple acyclic starting materials in a single step is highly desirable. [3,4] Herein, we report an organocatalytic domino reaction of 1,4-dien-3-ones 1 with ethyl isocyanoacetate (2; Scheme 1).…”

“…[1][2][3] Therefore, the development of a new strategy for the efficient construction of the azabicyclic skeleton from simple acyclic starting materials in a single step is highly desirable. [3,4] Herein, we report an organocatalytic domino reaction of 1,4-dien-3-ones 1 with ethyl isocyanoacetate (2; Scheme 1). This new general approach allows, in a single reaction, the formation of three C À C and one CÀN bonds in a regio-and diastereoselective manner, which provides efficient access to the azabicyclic compounds 3-the motif in pyrrolizidine alkaloids.…”

“…This new general approach allows, in a single reaction, the formation of three C À C and one CÀN bonds in a regio-and diastereoselective manner, which provides efficient access to the azabicyclic compounds 3-the motif in pyrrolizidine alkaloids. [1][2][3] In general, the one-pot tandem strategy is used to improve the efficiency of a chemical reaction whereby multiple bonds and stereocenters are formed in a single reaction without the need to isolate intermediates. [4] Our research in this area [5,6] has shown that 1,4-dien-3-ones of the type 1 can be used as versatile building blocks for the efficient construction of a wide variety of carbo-and heterocycles.…”

Asymmetric syntheses of functionalized pyrrolizidin-3-ones

“…6 The synthesis of pyrrolizidin-3-ones mono-or disubstituted at positions 1 or 7 was reviewed in 2000. 7 We have been interested in the preparation of such systems, in particular the (1R,7aS)-and (1S,7aS)-1-hydroxypyrrolizidin-3-ones (1 and 2) on one hand, and in a second line of study the O-protected (7S,7aS)-and (7R,7aS)-7-hydroxypyrrolizidin-3-ones (3 and 4) ( Figure 1). After treatment of 8 with TFA, the intermediate pyrrolidine was treated with potassium carbonate to give the expected (1S)-hydroxypyrrolizidin-3-one 2 (94% for the 2 steps) (Scheme 2).…”