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Mechanistic Study on Rearrangement Cascades Starting from Annulated 2‐Aza‐hepta‐2,4‐dienyl‐6‐ynyl Anions: Formation of Aniline and Azepine Derivatives
Author(s) -
Lyaskovskyy Volodymyr,
Fröhlich Roland,
Würthwein ErnstUlrich
Publication year - 2007
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200601491
Subject(s) - chemistry , lithium diisopropylamide , deprotonation , imine , benzonitrile , medicinal chemistry , nucleophilic addition , azepine , allylic rearrangement , intramolecular force , transmetalation , nitrile , iminium , enamine , quinoline , stereochemistry , organic chemistry , ion , catalysis
Deprotonation of benzothiophene‐derived alkynyl imine 11 with lithium diisopropylamide (LDA) and subsequent transmetalation with ZnCl 2 etherate furnished azepine 12 upon aqueous workup. Similarly, alkynyl benzaldimine 1 a gave a mixture of benzazepine 13 and naphthylamine 14 . Allylic benzonitriles 15 a , b reacted to produce naphthylamine 16 upon deprotonation with LDA at room temperature. In an analogous manner, imino benzonitrile 17 may be converted into 4‐amino isoquinoline 18 by means of an intramolecular nucleophilic attack on the nitrile function upon treatment with LDA. The allylic benzonitriles 19 a , b were prepared by LDA treatment of alkynyl imine 11 . They were further converted to amino dibenzothiophene 20 by LDA deprotonation and aqueous workup. These various transformations represent the key steps of a multistep reaction cascade, which was previously postulated on the basis of quantum chemical calculations. Thus, all features of this complex rearrangement mechanism could now be confirmed experimentally. DFT calculations support the lower reactivity of zinc species in the ring‐opening step compared to the lithium intermediates. All new compounds were completely characterized by spectroscopic data, including X‐ray diffraction studies for the key compounds 12 , 19 a , and 20 .