Communication
led to product with a relatively low yield (Table 2, entry 10). It
is notable that this chemistry could also be extended to the
synthesis of disubstituted 3-coumaranones 4m–4o with rea-
sonable yields (Table 2, entries 12–14).
with 3,4-dimethoxybenzaldehyde in basic conditions, followed
by demethylation with BBr3, provided the natural product sul-
furetin 10, which exerts diverse biological activities, such as
anti-nociceptive, anti-oxidant, anti-mutagenic, and anti-diabetic
activities.[1a,18]
We then considered the possibility of extending the reaction
to internal alkynes. However, no formation of the desired 3-
coumaranone was observed under the above optimized reac-
tion conditions. As shown in Equation (2) and Equation (3), the
treatment of substrate 3p only led to the isolation of a,b-unsa-
turated ketone 7[15] in 85% yield while only diketone com-
pound 8 was formed upon treatment of substrate 3q.[16] In
spite of this, these alkylated or arylated 3-coumaranones might
be readily achieved from the 3-coumaranone 4a according to
the known procedures.[17]
The mechanism[19] accounting for the oxidative formation of
3-coumaranones is depicted in Scheme 3, based on experimen-
tal observations and DFT computations (Figure 1, see the Sup-
porting Information for details). Initially, coordination of sub-
strate 3a to the catalytic gold(I) species forms the gold-alkyne
complex IA. This allene-like intermediate is subject to nucleo-
philic attack of the N-oxide, forming the alkenyl gold inter-
mediate II. Subsequent NÀO bond cleavage was noteworthily
found by DFT computations to give directly the oxonium ylide
intermediate IV,[20,21] thus bypassing the presumed a-oxo gold
carbene intermediate III.[22] Proto-demetallation and demethy-
lation from intermediate IV would furnish the final 3-coumara-
none 4a. The accompanying MsOMe could be detected from
1
the crude H NMR in all cases. Competitively, an N-oxide-free
pathway (Scheme 3) could be initiated by 1,5-cyclization within
the gold-alkyne complex IB, followed by protodemetallation
and demethylation of the as-formed benzofuran-3-yl gold in-
termediate V to afford benzofuran 2a as side product. Howev-
er, preliminary DFT computations showed that starting from
the gold-alkyne intermediates, the formation of oxonium ylide
intermediate IV is quite exothermic (À28.3 kcalmolÀ1) and irre-
versible, while formation of benzofuran-3-yl gold intermediate
3-Coumaranones have been demonstrated well as key pre-
cursors in the synthesis of aurones, which exist in a number of
natural products and bioactive molecules. As outlined in
Scheme 2, for example, condensation of 3-coumaranone 4k
V
is endothemic (13.9 kcalmolÀ1
) and highly reversible
(Scheme 3). That is, the N-oxide-involving pathway affording 3-
coumaranone 3a (with an acti-
vation barrier of ~14.4 kcal
molÀ1) is both thermodynamical-
ly and kinetically favored over
the N-oxide-free pathway that
affords byproduct benzofuran
2a (with an activation barrier of
18.0 kcalmolÀ1).
Scheme 2. Synthetic applications.
In summary, we have devel-
oped a practical and general so-
lution for the synthesis of vari-
ous 3-coumaranones via a gold-
catalyzed intermolecular oxida-
tion of alkynes. The utility of this
methodology is demonstrated
by the synthesis of the natural
product sulfuretin. Moreover,
theoretical investigations on the
reaction pathways for this oxida-
tive cyclization were also per-
formed. The high flexibility,
broad substrate scope, and mild
nature of this reaction and, in
particular, the absence to ex-
clude moisture or air (’open
flask’) render it a viable alterna-
Scheme 3. Mechanistic proposal for the gold-catalyzed synthesis of 3-coumaranones (left) and benzofuran (right).
Relative free energies (in kcalmolÀ1, in DCE at 298 K) of key intermediates and transition states given in parenthe-
ses were computed at the SMD-M06/6-31+G*&SDD(Au) level of theory with L=PH3 and [N]=pyridine.
tive for the synthesis of syntheti-
cally useful 3-coumaranones.
[23]
Chem. Asian J. 2014, 9, 1 – 6
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