Biomimetic Approach toward the Total Synthesis of rac-2-(Acylmethylene)pyrrolidine Alkaloids

Abstract

2-(Acylmethylene)pyrrolidine derivatives were synthesized via intermolecular decarbonylative Mannich reaction from various methyl ketones and 1-alkyl-1-pyrroliniums, generated in situ from 1-alkylprolines. This approach mimics the biosynthetic pathway and provides a direct access to a series of 2-(acylmethylene)pyrrolidine alkaloids, including hygrine, N-methylruspolinone, dehydrodarlinine, and ruspolinone.

A Potentially Limitless Chiral Pool via Conglomerate Crystallisation: Unidentified Spontaneous Resolution in the CSD.

“…Within this list are C2 symmetrical pyrimidine (OBIPAR [76] ), phosphine (LUSZOO [77] ) and imidazole (ROJPOW [78] ) ligands, an atropsiomeric quinoline (TUWFAT [79] ), an α-methylpyridine (DOBWUN [80] ), and a chiral salen ligand (TUNMOF [81] ). Potential types of organocatalysts such as the C2 symmetrical diol (NULZEA [82] ), a PTC (phase transfer catalyst) crown ether (NOCNIC [83] ), and chiral phosphoric acid (CUVGAB [84] ), chiral ureas (RIPBUN, [85] AZUDAB [86] ), benzotetramisole (YAMBAS [87] ), amino-alcohol (HARFEN [88] ), and imidazole (PURJUJ [89] ) may also find use in asymmetric synthesis. These are only selected examples, and we would encourage the community to view our full list of structures they may deem useful to their research.…”

Copper-catalyzed aerobic decarboxylative coupling between cyclic α-amino acids and diverse C–H nucleophiles with low catalyst loading

“…16204 | RSC Adv., 2018,8,[16202][16203][16204][16205][16206] This journal is © The Royal Society of Chemistry 2018…”

“…1e ). 8 In addition, significant progress has been achieved in visible-light-induced radical decarboxylative functionalization of α-amino acids including proline derivatives ( Fig. 1f ).…”

Norhygrine Alkaloid and Its Derivatives: Synthetic Approaches and Applications to the Natural Products Synthesis

“…The advantage of the proposed method is that the synthesis proceeded only in three stages and resulted in a high yield of the enantiomerically pure product with the use of commercially available tert-butyl pyrrolidine-1-carboxylate (3) as a starting compound. [28] In 2015, Tun-Cheng Chien and collaborators [29] reported the synthesis of a wide range of 2-(acylmethylene)pyrrolidine derivatives 8, including hygrine and ruspolinone. The proposed method involves decarboxylation of a carboxylic acid 7 followed by the reaction with various ketones, resulting in pyrrolidines 8 as a mixture of enantiomers (Scheme 3,a).…”