%0 Journal Article
%A Padwa, Albert
%A Kappe, C. Oliver
%A Cochran, John E.
%A Snyder, James P.
%D 1997
%T Studies Dealing with the Cycloaddition/Ring Opening/Elimination
Sequence of 2-Amino-Substituted Isobenzofurans†
%U https://acs.figshare.com/articles/journal_contribution/Studies_Dealing_with_the_Cycloaddition_Ring_Opening_Elimination_Sequence_of_2-Amino-Substituted_Isobenzofurans_sup_sup_/3705462
%R 10.1021/jo962358c.s001
%2 https://acs.figshare.com/ndownloader/files/5795910
%K amine vs amide influence
%K amido carbonyl group
%K Diel
%K DFT
%K isobenzofuran
%K intramolecular cycloaddition
%X The α-thiocarbocation generated from the Pummerer
reaction of an o-amido-substituted sulfoxide
is intercepted by the adjacent amido carbonyl group to produce a
2-amino-substituted isobenzofuran
as a transient intermediate. In the presence of an
electron-deficient dienophile, the reactive
isobenzofuran undergoes a Diels−Alder cycloaddition followed by ring
opening to furnish a
vinylogous C-acyliminium ion that readily aromatizes.
The one-pot intramolecular cascade process
only occurs either if the olefinic tether is activated by an ester or
if a carbonyl group is located
adjacent to the nitrogen atom of the 2-amino-substituted isobenzofuran.
To examine the amine vs
amide influence on the course of intramolecular cycloaddition, density
functional theory (DFT)
calculations have been carried out for both ground and transition
states. The results strongly
suggest that the amide-substituted isobenzofurans are destabilized by
steric effects between the
aromatic ring and the nitrogen-containing side chain. Raising of
the ground-state amide energies
thereby reduces the activation energy for internal cycloaddition and
leads to Diels−Alder adducts
more rapidly than for the corresponding amines. Amide tethers
emerge as remote-site promoters
of intramolecular cycloaddition for tandem processes yielding products
with multiple fused rings.
%I ACS Publications