(R)-DM-SEGPHOS–Ag(I)-Catalyzed Enantioselective Synthesis of Pyrrolidines and Pyrrolizidines via (1,3)- and Double (1,3)-Dipolar Cycloaddition Reactions

Abstract

An efficient diastereo- and enantioselective route to access a wide range of highly substituted pyrrolidine and pyrrolizidine derivatives has been described via (1,3)- and double (1,3)-dipolar cycloaddition reactions catalyzed by the (R)-DM-SEGPHOS-Ag(I) complex. The reactions proceed smoothly at ambient temperature, affording a variety of pyrrolidines and pyrrolizidines in high yields (up to 93%) with up to 99:1 dr and excellent enantioselectivities (up to 98% ee) without any additives. The newly synthesized pyrrolidine and pyrrolizidine derivatives contain four and seven contiguous stereogenic centers, respectively. Moreover, the synthetic utility of enantioenriched products has been demonstrated by transforming them into various synthetically useful advanced intermediates.

Acid‐Catalyzed Intramolecular Imination / Nucleophilic Trapping of 4‐Aminobutanal Derivatives: One‐Pot Access to 2‐(Pyrazolyl)pyrrolidines

“…As a rule, these reactions proceed with a high degree of stereoselectivity, which is achieved by employing complex chiral metal catalysts. As a typical example, the 1,3‐dipolar cycloaddition of glycine imines to ( E )‐3‐phenyl‐1‐(1 H ‐pyrazol‐1‐yl)prop‐2‐en‐1‐one in the presence of a chiral Ag I complex can be mentioned.…”

Iodine/K2CO3-catalyzed synthesis of multisubstituted pyrrolidine-2-carboxylates via a one-pot reaction between an araldehyde, an amino acid ester, and a chalcone

“…Ethyl 4-benzoyl-3,5-diphenylpyrrolidine-2-carboxylate ( 4a ): 29 White solid (92.9 mg, 93% yield); m.p. 130–132 °C (Lit.…”

“…130–132 °C (Lit. 29 126–129 °C); 1 H NMR (500 MHz, CDCl 3 ) δ: 7.56 (d, J = 7.2 Hz, 2H), 7.41 (dd, J = 9.3, 7.4 Hz, 3H), 7.35 (m, J = 7.7 Hz, 2H), 7.26 (dd, J = 14.9, 7.3 Hz, 3H), 7.11 (m, 5H), 5.02 (d, J = 8.8 Hz, 1H), 4.60–4.51 (t, J = 8.7 Hz, 1H), 4.28 (dq, J = 10.7, 7.1 Hz, 1H), 4.21–4.16 (m, 1H), 4.13 (dd, J = 7.8 Hz, 2H), 1.19 (t, J = 7.1 Hz, 3H).…”

Synthesis of pyrrolizidines and indolizidines by multicomponent 1,3-dipolar cycloaddition of azomethine ylides

“…Sing and co-workers has recently performed a double consecutive 1,3-DC by synthesizing firstly prolinates 93 by enantiocatalyzed 1,3-DC of glycine imino esters with α,β-unsaturated pyrazolamides using the chiral complex formed by (R)-DM-SEGPHOS (92) and AgOTf (Scheme 16) [62]. Afterwards, cinnamaldehydes and maleimides were added to the reaction flask providing pyrrolizidines 94 in moderate to high endo-diastereoselectivity.…”

“…These three-component 1,3-DC took place in toluene at rt or 70 °C, depending on the dipolarophile, affording mixtures of diastereomers with de up to >99 %. In the case of cinnamaldehyde and N-methyl or N-phenyl maleimides, pyrrolizidines endo- 62 A different multicomponent 1,3-DC has been described by Sridharan and co-workers [49] using benzylic alcohols instead of aldehydes. This reaction must be carried out under Ir catalysis, so a hydrogen autotransfer generated in situ the corresponding aldehyde, which by reaction with proline and maleimide, afforded a ca.…”