Journal of the American Chemical Society
Communication
a
zinc plate as cathode and anode, respectively, in MeCN with
an applied cell voltage of 3.2 V under blue LED irradiation. A
set of control experiments revealed that current, light, and
DCA are all necessary for reactivity (entries 2−4). Pyridine,
which is known to coordinate to B2pin2 and promote the
formation of a B-centered persistent radical intermediate,13a,14
was beneficial to reaction efficiency (entry 5).
Table 2. Scope of Electrophotocatalytic Borylation
We found that the use of white CFL was also productive
(entry 6), albeit with slightly reduced efficiency relative to the
blue LEDs. Changing the sacrificial anode from Zn to Al did
not significantly affect the reaction yield (entry 7). The
reaction, in principle, can be conducted in an undivided cell,
which indeed provided the desired product in 37% yield.
However, the reaction was prematurely terminated due to the
formation of a zinc bridge between the cathode and anode that
short-circuited the electrochemical setup (entry 8). Anthra-
quinone (AQ), which exhibits similar light-induced redox
reactivities,9 was also an effective catalyst, albeit with
diminished yield (entry 9). Importantly, this reaction was
also applicable to the reductive borylation of 4-chloroanisole
(3), which has a highly negative reduction potential (Ered
=
−2.90 V vs SCE)15 (entry 10). This result highlights the
extreme reducing power that this catalytic system can provide.
Notably, this substrate has not been successfully engaged in
high yielding reductive functionalizations using photoredox
catalysis.
We have found that this reaction is capable of borylating a
wide range of aryl halides. A number of functional groups
potentially sensitive to strongly reducing conditions, such as
ester (2 and 5), ketone (6), amide and carbamate (7 and 12),
thiophene (14), and N-Boc indole16 (15) groups, were well
tolerated (see Table 2). Notably, substrate 16 with an acidic
C−H bond α to the ester group underwent desired
transformation without epimerization of the stereogenic center.
These results showcase that, although our catalytic strategy
grants access to extremely reducing potentials, it does so under
catalyst control with a high level of chemoselectivity that is
typically uncommon in reactions promoted by potent reducing
metals. In principle, the same types of products could be
obtained using Pd-catalyzed borylation. Nevertheless, this
metal-catalyzed method17 provided substantially lower yield
for substrates bearing multiple Lewis basic coordinating groups
(e.g., 16−18).18 When applied to the functionalization of
indomethacin methyl ester, a pharmaceutical agent, 35% of the
desired borylate was isolated (18).
We note that certain aryl chlorides were poorly reactive and
returned the majority of the starting material, despite the fact
that their reduction potentials suggest that they would be
suitable substrates. We reason that in these cases, back electron
transfer from intermediate [Ar−Cl•−] to DCA is sufficiently
fast to outcompete scission of the C−Cl bond. This hypothesis
led us to investigate the corresponding aryl bromides. As
expected, the reductive borylation activity was restored. An
intramolecular competition experiment revealed that the
mesolytic cleavage of a C−Br bond is indeed substantially
faster than that of a C−Cl bond, as 1-chloro-4-bromobenzene
(19) was selectively transformed to borodebrominated product
20.
a
Isolated yields are reported. Optimal conditions from Table 1 used.
b
c
Calculated Ered values for aryl chlorides (see SI). 10 mol% DCA.
d
e
Yield determined by 1H NMR. Ered could not be accurately
f
determined. Aryl halide (0.25 mmol, 1 equiv), Pd(dppf)Cl2 (5 mol
%), KOAc (3.0 equiv), B2pin2 (1.2 equiv) in DMSO (0.85 mL) under
110 °C for 12 h.
highly challenging substrates for single electron reduction,8 yet
were productive under the optimal conditions.
The synthetic utility of this electrophotocatalytic protocol
was further expanded to the formation of C−Sn and C−C
bonds by employing different radical trapping agents (Table
3). For example, using hexamethylditin as a coupling partner,
we developed metal-free stannylation of aryl halides (22−26).
Using N-methylpyrrole or 1,4-difluorobenzene, C−H arylation
products (27−30) were isolated in moderate to high yields.
A mechanistic rationale is shown in Figure 2A (pathway A).
Thus, the DCA catalyst undergoes cathodic reduction to
generate DCA•−, which is then photoexcited to generate
DCA•−*.8e This highly reducing species can then donate an
electron to the π-system of the aryl halide9 to furnish
intermediate 31 and to regenerate the DCA catalyst. Aryl
halide radical anions 31 are known to undergo mesolytic
cleavage to form aryl radicals 32,19 which can then proceed to
the functionalized products.
Notably, in addition to haloanisoles, several other electron-
rich arenes and hetereoarenes (11−15) were found to be
suitable substrates. Some of these aryl halides (e.g., 10, 11, 12,
15) display very negative reduction potentials and represent
C
J. Am. Chem. Soc. XXXX, XXX, XXX−XXX