tion, cycloaddition,4e-g and miscellaneous reactions.4h,i To
our surprise, transition-metal-catalyzed cross-coupling using
ZIC as an electrophile has not been reported, although 1,4-
zwitterionic structure 3 has a structural similarity to the
iodonium salt (iodonium cation is compensated by an
external anion), which has been widely used in cross-
coupling in recent years.5
As a privileged scaffold, coumarin is a ubiquitous subunit
in many natural products with remarkable biological activities
and unique physical properties.7 Methodology toward its
synthesis has attracted considerable interest during the past
decade.8 We report herein the utilization of coumarin-based
zwitterionic iodonium compounds as effective electrophiles
in the palladium-catalyzed Suzuki-type coupling with various
aryl boronic acids to generate 3-substituted coumarins.
Strategically, we would like to generate our coumarin
library by introducing diversities at C-3 and C-4 positions-
(Figure 1), which would be more efficient than the construc-
ing 4-hydroxycoumarin derivatives.9e,f However, methods for
the synthesis of 3-substituted coumarins from coumarin
scaffolds are limited to a few examples, such as ligand
coupling reaction10 and transition-metal-catalyzed cross-
coupling reaction of 3-bromocoumarins with some organo-
metallics.9a Neverheless, the above-mentioned methods are
either less efficient or associated with toxic reagents.11
Although compound 4 was prepared more than twenty
years ago, its synthetic application was limited to a few
examples of diversified coumarin scaffolds.10 Since the vinyl
or diaryl iodonium salts are remarkable substituents for vinyl
or aryl halides or triflates in the transition-metal-catalyzed
cross-coupling,5 we anticipated that the coumarin-based
phenyl iodonium zwitterion 4 (Scheme 2) may have a similar
Scheme 2
property. Considering its pronounced thermoinstability,12 we
preferred to select the palladium-catalyzed Suzuki-type
coupling reaction to test our hypothesis, since this reaction
can be carried out at room temperature.
Figure 1. Retrosynthetic analysis of coumarin library.
Initially, we evaluated the Suzuki reaction by coupling of
compound 4 with 4-methoxyphenylboronic acid using 10 mol
% of Pd(PPh3)4 as a catalyst (Scheme 2).5 Gratifyingly, this
reaction indeed proceeded to give compound 5, albeit in a
low yield (10%), concurrent with the starting material
recovered.
tion of the diversified lactone moiety by condensation of the
preassembled acyclic precursors.9
We have previously developed the chemistry for diversi-
fication of coumarin at the C-4 position from its correspond-
We then focused on improving the reaction yield. Pro-
longing the reaction time gave no improvement of the yield
at all. Increasing the loading level of Pd(PPh3)4 resulted in
an even poorer yield of desired compound 5. On the contrary,
increased concentration of Pd(PPh3)4 led to a significant
amount of a side product, which was finally identified as
the phosphonium ylide 6 (Scheme 2), derived from transyli-
dation of triphenylphosphine from catalysts Pd(PPh3)4 with
iodonium ylide 4.13
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