Asymmetric Catalytic Aziridination of Cyclic Enones

Abstract

The first catalytic method for the asymmetric aziridination of cyclic enones is described. The presented organocatalytic strategy is based on the use of an easily available organocatalyst that is able to convert a wide range of cyclic enones into the desired aziridines with very high enantiomeric purity and good chemical yield. Such a method may very well open up new opportunities to stereoselectively prepare complex chiral molecules that possess an indane moiety, a framework that is found in a large number of bioactive and pharmaceutically important molecules.

Use of (R)-Mandelic Acid as Chiral Co-Catalyst in the Michael Addition Reaction Organocatalyzed by (1S,4S)-2-Tosyl-2,5-diazabicyclo[2.2.1]heptane under Solvent-Free Conditions

“…[34] More recent applications of the ACDC principle have been developed by Melchiorre et al, who used a salt derivative of cinchona alkaloids with different N-Boc protected amino acids to catalyze a variety of reactions with selected nucleophiles. [35][36][37][38][39] In this context, Xu and coworkers employed a combination of (S)-prolinamine and (R)-tert-leucine to catalyze the asymmetric reaction between salicylic acid and 2-cyclohexen-1-one. [40] Very recently, Jørgensen and Albrecht studied the Morita-BaylisHillman reaction catalyzed by a quinine derivative in combination with (S)-mandelic acid.…”

Enantioselective Preparation, Conformational Analysis and Absolute Configuration of Highly Substituted Aziridines

“…Due to our great interest in the study of enantioselective aziridination reactions, we decided to pursue the challenging issue represented by the construction of chiral aziridines obtained from highly encumbered linear enones. This reaction would represent a novelty not only for the use of such trivial substrates but also for the structure of the resulting aziridines that are characterized by adjacent tertiary and quaternary stereocenters.…”

“…We started our investigation using well‐established conditions for aziridination type reaction . No reaction was observed by reacting 3‐methyl‐3‐penten‐2‐one 1a in chloroform with benzyl (tosyloxy)carbamate 2a in the presence of 9‐ epi ‐9‐amino‐9‐deoxy‐dihydroquinine A in combination with d ‐ N ‐Boc‐phenylglycine F at RT for 48 h. We then increased the temperature to 50°C and were pleased to obtain 88% yield in the desired aziridine , with a 4:1 diastereomeric ratio in favor of the major syn ‐diastereoisomer 3a , and a moderate 60% enantiomeric excess (Scheme ).…”

“…21,22 For this reason it is not surprising that many research groups focused their efforts on the aminocatalytic synthesis of such important scaffolds. α,β-Unsaturated aldehydes [23][24][25] (Scheme 1a) and linear or cyclic α,β-unsaturated ketones 26,27 (Scheme 1b,c) are privileged substrates that undergo aziridination reaction with different catalytic systems. Enals are generally activated using proline-derived secondary amines catalysts, 28 while enones require the use of primary amine catalysts.…”

Asymmetric Organocatalytic Aziridination: Recent Advances

“…In 80’s Wynberg and co‐workers established the high versatility of Cinchona alkaloids as “organic chirality inducers”, a role that have been constantly endorsed by their broad application in various and different research areas. Among others, Bencivenni and Melchiorre following their pioneering work concerning catalyst primary amine salts, further assessed the feasibility of their organocatalytic aziridination strategy by broadening the reaction substrate scope to both cyclic enones 56 and α‐branched α,β‐unsaturated ketones 61 (Scheme ) . The illustrated results undoubtedly ( i ) clarified the utility of chiral primary amines 57 and 58 in the presence of proper acid additives ( 59 , ent ‐ 59 , 62 ) as organocatalysts, which gave a fascinating stereoselective access to a variety of complex N ‐Boc‐protected aziridine derivatives 60 and ent ‐ 60 (53–98%Y, 61–99% ee ), and (ii) confirmed the challenging difficulties in the activation of hindered carbonyl compounds 61 (R=Me, 60%Y, d.r.…”