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Irreversible endo ‐Selective Diels–Alder Reactions of Substituted Alkoxyfurans: A General Synthesis of endo ‐Cantharimides
Author(s) -
Foster Robert W.,
Benhamou Laure,
Porter Michael J.,
Bučar DejanKrešimir,
Hailes Helen C.,
Tame Christopher J.,
Sheppard Tom D.
Publication year - 2015
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.201406286
Subject(s) - cycloaddition , furan , chemistry , heptane , alkoxy group , diels–alder reaction , alkyl , organic chemistry , medicinal chemistry , catalysis
Abstract The [4+2] cycloaddition of 3‐alkoxyfurans with N‐substituted maleimides provides the first general route for preparing endo ‐cantharimides. Unlike the corresponding reaction with 3 H furans, the reaction can tolerate a broad range of 2‐substitued furans including alkyl, aromatic, and heteroaromatic groups. The cycloaddition products were converted into a range of cantharimide products with promising lead‐like properties for medicinal chemistry programs. Furthermore, the electron‐rich furans are shown to react with a variety of alternative dienophiles to generate 7‐oxabicyclo[2.2.1]heptane derivatives under mild conditions. DFT calculations have been performed to rationalize the activation effect of the 3‐alkoxy group on a furan Diels–Alder reaction.