1,3‐Dipolar cycloadditions of azomethine ylides with dipolarophiles. II. Synthesis of pyrrolizidines

Abstract

Substituted pyrrolizidines have been synthesized by 1,3‐dipolar cycloaddition of various dipolarophiles with the azomethine ylide generated by treatment of proline with benzaldehyde in dimethylsulfoxide. The regio‐ and stereochemical outcome of the reaction as well as the stability of the isomers obtained are discussed.

1,3-Dipolar Cycloaddition Reactions of Azomethine Ylides with Carbonyl Dipolarophiles Yielding Oxazolidine Derivatives

“…Minor amounts of the corresponding oxazolidine cycloadducts have also been isolated as side products from reactions involving (a) sarcosine, phenylglyoxal and N-ethylmaleimide [98]; and (b) (S)-(−)-2-azetidinecarboxylic acid, phenylglyoxal and dimethyl fumarate [99].…”

“…Minor amounts of the corresponding oxazolidine cycloadducts have also been isolated as side products from reactions involving (a) sarcosine, phenylglyoxal and N-ethylmaleimide [98]; and (b) (S)-(´)-2-azetidinecarboxylic acid, phenylglyoxal and dimethyl fumarate [99]. An intramolecular variant that involves the generation of non-stabilized azomethine ylides from the condensation of α-amino acids with aldehydes bearing a tethered carbonyl group has also been reported.…”

Synthesis of benzopyranopyrrolidines via 1,3-dipolar cycloaddition of nonstabilized azomethine ylides with 3-substituted coumarins

“…In the case of trans-fusion in the pyrrolizidine 10c, this proton was observed at a 0.65 ppm higher magnetic field than that of 9c with cis-fusion, probably due to a shielding effect of the benzene ring. 4,7 In addition, a strong NOE cross-peak was observed between H(11a)eH(11b) in isomer 9c. The structures of products 8e11 were confirmed by elemental analyses, HRMS, 13 C NMR spectra as well as 2D 1 He 13 C HMQC and HMBC experiments.…”

“…Alternatively, major diastereomers were purified by crystallization of the crude mixture of oxalates from acetone or ethanolewater. 6-oxo-6,6a,6b,7,8,9,11,11a- 7,25.5,28.0,40.0,55.9,60.3,62.9,69.6,116.6,118.8,125.2,129.5,129.6,150.0,163.4 (CO) -6-oxo-6,6a,6b,7,8,9,11,11a-octahydrochromeno[3,4-a]pyrrolizine-6a-carboxamide oxalate (8d). Yield 60%, a pale yellow powder, mp 147e152 C (ethanol).…”

“…4.4.5. Diethyl ((6aR*,6bR*,6a,6b,7,8,9,11, 4.4.6. Diethyl ((6aR*,11aR*,11bS*)-6-oxo-6,6a,7,9,10,11,11a,11b-octahydrochromeno [4,3-a] C,63.22;H,5.19;N,3.21.…”