Total synthesis of both enantiomers of (−)-(2S,3R,6S)- and (+)-(2R,3S,6R)-microgrewiapine A along with (+)-microcosamine A and (−)-6-epi-microgrewiapine A from chiral 1-(α-methylbenzyl)-aziridine-2-carboxylate was accomplished for the first time. Key steps involved in this synthesis include one-pot reductive ring-opening of aziridine, debenzylation, intramolecular N-alkylation to obtain the key piperidine ring, and Julia–Kociensky olefination. The absolute configuration of natural microgrewiapine A is assigned as (+)-(2R,3S,6R), which is opposite to the originally proposed structure by comparing optical rotation data of both synthetic enantiomers.

The synthetic methods to build the 2,6-disubstituted piperidine structural motif were described focusing on stereochemical control of two substituents at C2 and C6 with specific examples of natural products.

This is the first report on an intramolecular C-N bond formation of an amide-tethered benzylic/allylic system using DDQ under neutral conditions which has been successfully applied to the total synthesis of naturally occurring pyrolidine alkaloids. The key steps for the synthesis of corresponding precursors involve Julia-Kociensky olefination/cross-metathesis and dihydroxylation reactions, and this methodology is also extended to the ω-unsaturated N-sulfanilamide to furnish piperidines.

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