Investigation of the Lewis acid mediated stereoselective cyclization of cationic aminyl radicals leading to substituted pyrrolidines

Copper(I) Catalysts for the Stereoselective Addition ofN-Chloroamines to Double Bonds: A Diastereoselective Radical Cyclisation

“…As the aminyl radical is coordinated to the catalyst in the addition step,9 an influence of the catalyst structure and ligand sphere on the stereochemical outcome of the reaction can be expected. This could allow an efficient radical cyclisation with a catalyst‐induced stereoselectivity 10…”

A New Method for Intramolecular Chloroamination of Unfunctionalized Olefins

“…Somfai et al. showed that, in the presence of the Lewis acid‐TiCl 3 system, chloroamines were able to undergo intramolecular free radical cyclizations at low temperature, giving the corresponding 2‐chloromethylpyrrolidines in good to excellent yields 10…”

“…The amount of 2b′ was increased when concentrating the reaction mixture at elevated temperature, and refluxing 2b in THF resulted in a complete conversion of 2b to 2b′ . A clean NMR spectrum was sometimes difficult due to the conversion of 2b to 2b′ in chlorinated solvents such as CDCl 3 10. A low temperature is advantageous to avoid any unnecessary conversion of 2b to 2b′ when handling the reaction mixture, and NMR spectra should be recorded immediately after the sample has been prepared in CDCl 3 .…”

Modulation of Pharmacologically Relevant Properties of Piperidine Derivatives by Functional Groups in an Equatorial or Axial β‐Position to the Amino Group

“…The synthesis of the epimeric N ‐methyl 3‐( tert ‐butyl)‐5‐chloropiperidines, cis ‐ 16 and trans ‐ 16 , respectively, involved essentially a five‐step synthesis starting from the readily available methyl 2‐ tert ‐butylpent‐4‐enoate 43 (Scheme ), involving reduction of the methyl ester to the primary alcohol 44 , Swern oxidation to the aldehyde 45 , and reductive amination to the N ‐methylamine 46 with good overall yield. The latter was subjected to N ‐chlorination using N ‐chlorosuccinimide providing the N ‐chloroamine 47 in nearly quantitative yield. Due to chemical instability, this compound had to be used immediately without further purification.…”

“…Due to chemical instability, this compound had to be used immediately without further purification. Cyclization to the epimeric cis‐ and trans ‐pyrrolidine derivatives cis‐ / trans ‐ 48 was then achieved at low temperature using BF 3 ⋅ OEt 2 with a catalytic amount of TiCl 3 . The pyrrolidine product mixture was used without further purification and allowed to stand in chloroform at room temperature for about 3.5 days, after which their stereospecific rearrangements to the corresponding more stable epimeric β‐chloropiperidine derivatives, cis ‐ 16 and trans ‐ 16 , were complete.…”