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Assembly of the Bis(imidazolyl)propene Core of Nagelamides C and S by Double Grignard Reaction
Author(s) -
Jacobi Nicolas,
Lindel Thomas
Publication year - 2010
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201000625
Subject(s) - chemistry , imidazole , nitrile , electrophile , pyrrole , grignard reaction , ketone , stereochemistry , propene , medicinal chemistry , propargyl , organic chemistry , reagent , catalysis
As characteristic structural elements of several of the non‐monomeric pyrrole‐imidazole alkaloids, 1,1‐bis(imidazolyl)propenes were assembled in a facile manner by double Grignard reaction of metalated imidazoles with saturated esters, followed by dehydration. The presence of nitrile functions or acryl esters in the electrophile component leads to competing reactions, whereas propargyl esters are tolerated. Introduction of 2‐amino groups was possible via the corresponding dimethylsulfamoyl‐protected 2‐azidoimidazoles, which had to be deprotected prior to hydrogenation. NOESY‐based analysis revealed preferred orientation of the imidazole 5‐positions towards the propenyl chain.