Premium
Cyclopropyl Carbinol Rearrangement for Benzo‐Fused Nitrogen Ring Synthesis
Author(s) -
Kothandaraman Prasath,
Huang Chuhui,
Susanti Dewi,
Rao Weidong,
Chan Philip Wai Hong
Publication year - 2011
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.201101363
Subject(s) - hydroamination , cyclopropane , chemistry , moiety , ring (chemistry) , intramolecular force , catalysis , trifluoromethanesulfonate , medicinal chemistry , stereochemistry , aniline , organic chemistry
A synthetic method that relies on gold‐catalysed cyclopropyl carbinol rearrangement of 2‐tosylaminophenyl cyclopropylmethanols to prepare 2,3‐dihydro‐1 H ‐benzo[ b ]azepines and 2‐vinylindolines efficiently is reported. The reactions were shown to be chemoselective, with secondary and tertiary alcohol substrates exclusively providing benzo‐fused five‐ and seven‐membered ring products, respectively. The ring‐forming process was also found to proceed in moderate to excellent yields under mild conditions only in the presence of the gold and silver catalyst combination. The mechanism is thought to involve activation of the alcohol by the ( p ‐CF 3 C 6 H 4 ) 3 PAuCl/AgOTf (Tf=triflate) catalyst, resulting in ionization of the starting material. The tertiary carbocationic intermediate generated in situ in this manner then triggers ring‐opening of the cyclopropane moiety and trapping by the tethered aniline group to give the 2,3‐dihydro‐1 H ‐benzo[ b ]azepine. Cyclopropane ring fragmentation of the secondary carbocationic analogue, on the other hand, results in diene formation followed by subsequent intramolecular hydroamination to afford the 2‐vinylindoline.