Organic Letters
Letter
To probe the reaction mechanism, we performed several
control experiments. When 2.5 equiv of butylated hydrox-
ytoluene (BHT) was added to the reaction system, the yield of
3aa dropped to 46%, and the reaction was notably sluggish
(Scheme 4a). 3aa was not detected as 2.5 equiv of 2,2,6,6-
EDA complex between 1a and B(C6F5)3. By comparing the
spectra of 1a + B(C6F5)3 and 1a + 2a + B(C6F5)3, the
formation of the three-component EDA complex (1a + 2a +
B(C6F5)3) was excluded. The overlapping spectra of 2a and 2a
+ B(C6F5)3, 1a and 1a + 2a revealed that the other two-
component EDA complexes were not formed. Job’s plot
experiment supported the 1:1 stoichiometric ratio of the EDA
complex between 1a and B(C6F5)3. Light on/off experiments
showed that continuous visible-light irradiation is a necessity
On the basis of the control experiments, a possible
mechanism is proposed using 1a and 2a as model substrates
(Scheme 5). The reaction starts with the formation of an EDA
Scheme 4. Mechanistic Experiments
Scheme 5. Plausible Mechanism
a
Yields were determined by GC with n-hexadecane as an internal
b
standard. Isolated yield.
tetramethyl-1-piperidinyloxy (TEMPO) was added, and
compound 4 was obtained in 11% yield (Scheme 4b),
indicating that the reaction probably proceeds through a
free-radical process. However, when disulfide 5 was used as the
substrate instead of thiophenol, only a small amount of
product 3aa was obtained, indicating that the S−H proton of
thiol substrates is essential for the reaction (Scheme 4c). When
heated to 80 °C in the dark, the reaction cannot proceed,
indicating that the reaction is probably not thermally promoted
(Scheme 4d). In the presence of H2O2, the reaction could give
the desired product 3aa in 35% yield in the dark and under a
N2 atmosphere, whereas only a trace amount of product 3aa
was obtained without B(C6F5)3 (Scheme 4e,f). H2O2 also
progresses the reaction, especially in the presence of B(C6F5)3
as a background reaction in which light is not involved, but the
background reaction is not a major process under the
photocatalytic conditions.
complex between indole 1a and B(C6F5)3. Upon irradiation by
visible light, a SET process occurs in the EDA complex,
generating a radical ion pair, which can also undergo back-
electron transfer (BET)14a to regenerate the ground-state EDA
complex. B reacts with oxygen to generate intermediate C,
which abstracts a hydrogen atom from 2a to deliver
intermediate D and sulfur radical E. Hydrogen peroxide is
obtained by the protonation of complex D, and B(C6F5)3 is
released to accomplish the catalytic cycle. Hydrogen peroxide
oxidizes 2a and can also generate sulfur radical E and water.
Intermediate A reacts with E to give intermediate F, which is
directly deprotonated to furnish the final product 3aa.
In summary, we have developed a B(C6F5)3-catalyzed
photochemical reaction via an EDA complex for the
sulfenylation of indoles. The reaction does not require
transition metals and successfully realizes the cross-coupling
under aerobic conditions. The substrate scope is broad, and a
variety of functional groups are compatible. Mechanism studies
showed that the SET process in the EDA complex plays an
important role in the catalytic cycle of B(C6F5)3. Further
mechanistic studies and the application of this EDA complex
strategy in organic synthesis are currently under way in our
laboratory.
Because the color changed upon the mixing of B(C6F5)3
with indoles, UV−vis absorption spectroscopy analysis was
conducted (Figure 1). Upon mixing 1 equiv of recrystallized 1a
with a catalytic amount of B(C6F5)3 (5 mol %), a significant
color change was observed, accompanied by a bathochromic
shift in the UV−vis spectra, indicating the formation of an
ASSOCIATED CONTENT
■
sı
* Supporting Information
The Supporting Information is available free of charge at
Detailed experimental procedures, spectroscopic data,
copies of 1H NMR and 13C NMR spectra for all isolated
Figure 1. (a) UV−vis absorption spectra measured in DCE (0.1 M).
(b) Visual appearance of reaction components.
C
Org. Lett. XXXX, XXX, XXX−XXX