532985-81-2Relevant academic research and scientific papers
Diastereoselective preparation of 2,4,6-trisubstituted-2'-cyanopiperidines: application to the construction of the carbon framework of perhydrohistrionicotoxin.
Malassene, Richard,Vanquelef, Enguerran,Toupet, Loic,Hurvois, Jean-Pierre,Moinet, Claude
, p. 547 - 551 (2003)
The anodic cyanation of methanolic solutions of the 2-alkyl-N-phenylpiperidines 6b-d was performed in a flow cell equipped with a graphite felt anode. The reaction led to the formation of the 2-cyano-6-alkyl-N-phenylpiperidines 2b-d and proceeded with a high degree of regioselectivity. The 1H NMR spectra of the aminonitriles 2b-d showed an epimeric mixture at C-6. The major isomer has a trans configuration in which the cyano group is axial and the alkyl substituent is equatorial. Conversely, electrochemical oxidation of the 4-methyl-6-pentyl-N-phenylpiperidine 6e afforded the trisubstituted aminonitrile 2e as a single diastereomer (> 98% de). The 4-cyanobutyl side chain was incorporated in a two-step procedure to yield dinitrile 4e. This latter compound was directly converted into spiropiperidine 5e by using the Thorpe-Ziegler annulation procedure. The overall sequence (4 steps, 43%) allows the construction of the basic carbon framework of perhydrohistrionicotoxin.
N-phenyl-substituted pyrrolidines, piperidines and azabicyclics by a tandem reduction-double reductive amination reaction
Bunce, Richard A.,Herron, Derrick M.,Lewis, Jason R.,Kotturi, Sharadsrikar V.
, p. 113 - 120 (2007/10/03)
N-Phenyl-substituted pyrrolidines and piperidines have been synthesized by catalytic reduction of nitrobenzene in the presence of 4- and 5-oxoaldehydes, respectively. The process involves reduction of the aromatic nitro group to give the N-phenylhydroxylamine or aniline followed by reductive amination with the two carbonyl functional groups. Monocyclic systems are generally formed in high yield and are easily purified. The method has also been extended to the synthesis of fused N-phenylazabicyclics from 2-(3-oxopropyl)cycloalkanones. A high degree of diastereoselectivity for the trans-fused product is observed in substrates having an ester group α to the cycloalkanone carbonyl. Bicyclic precursors lacking this ester group give mixtures of cis and trans products. Finally, contrary to previous reports, we have demonstrated that aniline can be substituted for nitrobenzene in these reactions.
