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One‐Pot Synthesis of Metastable 2,5‐Dihydrooxepines through Retro‐Claisen Rearrangements: Method and Applications
Author(s) -
Zhang Wei,
Baudouin Emmanuel,
Cordier Marie,
Frison Gilles,
Nay Bastien
Publication year - 2019
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.201901675
Subject(s) - claisen rearrangement , sigmatropic reaction , chemistry , metastability , bicyclic molecule , selectivity , natural product , stereochemistry , combinatorial chemistry , medicinal chemistry , organic chemistry , catalysis
A one‐pot methodology to synthesize metastable bicyclic 2,5‐dihydrooxepines from cyclic 1,3‐diketones and 1,4‐dibromo‐2‐butenes through the retro‐Claisen rearrangement of syn ‐2‐vinylcyclopropyl diketone intermediates is reported. DFT calculations were performed to understand the reaction selectivity and mechanisms towards [1,3]‐ or [3,3]‐sigmatropic rearrangements, highlighting the crucial influence of the temperature. The reaction was successfully applied to a short protecting group‐free total synthesis of radulanin A, a natural 2,5‐dihydrobenzoxepine. Moreover, the strong herbicidal potential of this natural product is demonstrated for the first time.