Persistent free radicals have become indispensable in the synthesis of organic materials by living radical polymerization. However, examples of their use in the synthesis of small molecules are rare. Herein, we report the application of persistent radical and quinone methide intermediates to the synthesis of the resveratrol tetramers nepalensinol B and vateriaphenol C. The spontaneous cleavage and reconstitution of exceptionally weak carbon-carbon bonds has enabled a stereoconvergent oxidative dimerization of racemic materials in a transformation that likely coincides with the biogenesis of these natural products. The efficient synthesis of higher-order oligomers of resveratrol will facilitate the biological studies necessary to elucidate their mechanism(s) of action.
The
total synthesis of lundurines A–C has been accomplished
in racemic and enantiopure forms in 11–13 and 12–14
steps, respectively, without protection/deprotection of functional
groups, by a novel tandem double condensation/Claisen rearrangement,
a gold(I)-catalyzed alkyne hydroarylation, a cyclopropanation via
formal [3 + 2] cycloaddition/nitrogen extrusion, and a remarkable
olefin migration through a vinylcyclopropane retro-ene/ene reaction
that streamlines the endgame.
The intermolecular gold(I)-catalyzed
reaction between arylalkynes
and alkenes leads to cyclobutenes by a [2 + 2] cycloaddition, which
takes place stepwise, first by formation of cyclopropyl gold(I) carbenes,
followed by a ring expansion. However, 1,3-butadienes are also formed
in the case of ortho-substituted arylalkynes by a
metathesis-type process. The corresponding reaction of alkenes with
aryl-1,3-butadiynes, ethynylogous to arylalkynes, leads exclusively
to cyclobutenes. A comprehensive mechanism for the gold(I)-catalyzed
reaction of alkynes with alkenes is proposed on the basis of density
functional theory calculations, which shows that the two pathways
leading to cyclobutenes or dienes are very close in energy. The key
intermediates are cyclopropyl gold(I) carbenes, which have been independently
generated by retro-Buchner reaction from stereodefined 1a,7b-dihydro-1H-cyclopropa[a]naphthalenes.
Chiral gold(I) catalysts
have been designed based on a modified
JohnPhos ligand with a distal C
2-2,5-diarylpyrrolidine
that creates a tight binding cavity. The C
2-chiral element is close to where the C–C bond formation takes
place in cyclizations of 1,6-enynes. These chiral mononuclear catalysts
have been applied for the enantioselective 5-exo-dig
and 6-endo-dig cyclization of different 1,6-enynes
as well as in the first enantioselective total synthesis of three
members of the carexane family of natural products. Opposite enantioselectivities
have been achieved in seemingly analogous reactions of 1,6-enynes,
which result from different chiral folding of the substrates based
on attractive aryl–aryl interactions.
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