Deployment of Aziridines for the Synthesis of Alkaloids and Their Derivatives

Abstract

Various (activated and non-activated) aziridines with diverse substitution patterns have been deployed successfully as starting materials for the synthesis of a wide variety of alkaloids via suitable functionalization and aziridine ring transformation. Alternatively, the preparation and interception of reactive aziridine intermediates has also been shown to constitute a valid approach toward alkaloid synthesis. This review summarizes aziridine-mediated syntheses of alkaloids, in which the aziridine is mobilized as either a substrate or an advanced synthetic intermediate.1 Introduction2 Alkaloids Synthesis from Aziridine Starting Materials2.1 (2R)- and (2S)-Hydroxymethyl-N-(1-phenylethyl)aziridines2.2 N-Benzylaziridine-2-carboxylates2.3 2-Substituted N-Tosyl- or N-Tritylaziridines2.4 2,3-Disubstituted N-Cbz- or N-Tosylaziridines2.5 N-DMB-aziridines3 Alkaloids Synthesis from Aziridines as Key Advanced Synthetic Intermediates3.1 Alkylative Aziridine Ring Opening3.2 Arylative Aziridine Ring Opening3.3 Ring Expansion3.4 Oxidative Aziridine Ring Opening3.5 Heteroatomic Nucleophilic Aziridine Ring Opening3.6 Reductive Aziridine Ring Opening4 Conclusion

Substrate-Directed Enantioselective Aziridination of Alkenyl Alcohols Controlled by a Chiral Cation

“…In particular, the presence of the alcohol can allow for discrimination between the two ends of the aziridine, which are in some instances sterically and electronically very similar. It is also well known that aziridines are versatile building blocks, amenable to a range of post-functionalization protocols, which have been extensively discussed elsewhere . We first turned our attention to the derivatization of the aziridines obtained from the exo -dialkyl alkenes (Scheme ).…”

Catalytic Aminium Radical-Cation Salt (Magic Blue)-Initiated SN2-Type Nucleophilic Ring-Opening Transformations of Aziridines

“…Such compounds as electrophiles, in combination with appropriate nucleophiles, generate a number of interesting molecules of immense biological relevance . Aziridines with diverse substitution patterns could be successfully employed as starting materials for the synthesis of a wide variety of alkaloids, and other bioactive compounds via nucleophilic ring-opening followed by suitable chemical transformations. The nucleophilic ring-opening of activated aziridines with various O -nucleophiles would generate the corresponding alkoxy and alkanol amines having O and N at vicinal positions, which are the key structural motifs of various biologically active molecules (Figure ) and building blocks for other new compounds .…”

Alkylative Aziridine Ring-Opening Reactions

“…Aziridine, a nitrogen-containing three-membered ring, has high ring strain similar to oxirane and cyclopropane [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 ]. However, the non-activated aziridine-bearing electron donating group at the ring nitrogen is relatively stable and inert toward almost all nucleophiles.…”