2
C.-H. Shen et al. / Journal of Organometallic Chemistry xxx (2015) 1e5
Scheme 1. Initial design.
affording the corresponding [1,4]oxazino[3,2-b]indoles and 1H-pyr-
azino[2,3-b]indoleingoodtoexcellentyields.
Finally, a plausible mechanism to rationalize the catalytic
transformation is proposed, as depicted in Scheme 2. Taking sub-
strate 1a for example, the reaction probably starts with the coor-
dination of the gold catalyst to the alkyne, which would then
undergo the concomitant nucleophilic attack of the azide nitrogen
to generate intermediate A. The gold-carbenoid intermediate B is
expected to be formed at this stage via the release of molecular
nitrogen. Target compound 2a should thus be obtained via the
Results and discussion
We began our studies by choosing 1a as the model substrate to
examine the reaction and selected results are summarized in
Table 1. The influence of various gold catalysts bearing different
phosphine ligands was first screened (Table 1, entries 1e6). Pleas-
ingly, all the gold catalysts, such as [Ph3PAuNTf2, IPrAuNTf2, (4-
CF3C6H4)3PAuNTf2, Cy-JohnPhosAuNTf2, XPhosAuNTf2 and Brett-
PhosAuNTf2], did promote this transformation, leading to the target
compound 2a in good to excellent yields, and XPhosAuNTf2 was
best suited for this reaction to afford 2a in 91% yield (Table 1, entry
5). Importantly, no background oxazolidine formation via a gold-
catalyzed 5-exo-dig cyclization was observed in all cases. Of note,
non-noble metals such as Zn(OTf)2 and Cu(OTf)2 cannot catalyze
such a cascade cyclization and only hydration product was isolated
as the main product (Table 1, entries 7 and 8). In addition, the use of
other solvents such as THF and toluene led to a significantly
decreased yield (Table 1, entries 9 and 10).
intramolecular trapping of the a-imino gold carbenoid by the OH
moiety and the subsequent aromatization/deauration.
Conclusions
In summary, we have developed a facile and efficient solution
for the synthesis of [1,4]oxazino[3,2-b]indoles and 1H-pyrazino
[2,3-b]indoles via a gold-catalyzed tandem transformations of
(azido)ynamides. Importantly, in comparison with the related
oxidation approach to the generation of gold carbenes [4,5], this
strategy provides a more atom-economic way for the generation of
gold carbenes. The use of readily available substrates, a simple
procedure, and mild reaction conditions and, in particular, no need
With the optimal reaction conditions in hand (Table 1, entry 5),
the scope of the transformation was then explored. As shown in
Table 2, ynamide substrates 1 bearing electron-withdrawing or
electron-donating substituents such as Cl, Br, Me and MeO on the
phenyl ring were well compatible with this transformation, leading
to the efficient formation of the corresponding products [1,4]oxa-
zino[3,2-b]indoles in 89e93% yields (Table 2, entries 1e6). To
further illustrate the validity of our current methodology, an
experiment using 1g as the substrate was also carried out. Grati-
fyingly, the expected product 1H-pyrazino[2,3-b]indole 2g could
also be obtained in 80% yield (Table 2, entry 7). Thus, this cascade
cyclization provides a highly efficient and convenient route for the
construction of six-membered heterocycle-fused indole de-
rivatives, which may have applications in drug development and
chemical biology.
to exclude moisture or air (“open flask”) render these methods
potentially useful in organic synthesis. Further investigations into
the synthetic applications of the current reaction are in progress in
our laboratory.
Experiment section
Gold-catalyzed cascade cyclization of (azido)ynamides to [1,4]
oxazino[3,2-b]indoles
XPhosAuNTf2 (14.3 mg, 0.015 mmol) was added to a solution of
the ynamide 1 (0.30 mmol) in DCE (6.0 mL) at room temperature.
The reaction mixture was stirred at room temperature and the
progress of the reaction was monitored by TLC. The reaction typi-
cally took
6 h. Upon completion, the mixture was then
j.jorganchem.2015.01.029
Shen, Cang-Hai
