Journal of the American Chemical Society
Article
sodium ascorbate and photoirradiation as no product was
detected in the absence of either of them (entries 8 and 9).
Gram-scale synthesis was easily achieved by employing more
intensive light irradiation and a longer reaction time (entry
10), demonstrating the synthetic practicality of this method.
Scope of Borylation. With the optimized conditions in
hand, we examined the scope of borylation of aryl chlorides
through the ConPET process. We found that this protocol was
effective with not only activated aryl chlorides (15−25) but
also challenging nonactivated aryl chlorides (14) and electron-
rich aryl chlorides (3−13) that possess very negative reduction
potentials (up to −2.94 V, Table 2A). A number of functional
groups were well tolerated, including ethers (8−11), phenols
(12), sulfides (13), trifluoromethyl (24), and borates (25) as
well as those potentially sensitive to strongly reducing
conditions, such as aryl fluorides (16−19), nitriles (20−22),
esters (23), indoles (26), and epoxides (27). Only moderate
yields were obtained with some substrates (9 and 11−13),
which were mainly due to the competing dechlorination side
reaction and starting material recovery even with prolonged
reaction time (36 h). No obvious correlation between the
substrate reduction potential and reactivity was observed,
indicating the radical anion fragmentation and borylation steps
also played important roles to achieve an overall efficient
transformation.19 Diborylation products (25, 28, and 29),
which have found wide application in materials science, were
obtained in good to excellent yields when dihaloarenes were
employed, probably because the generated monoborylated
chloride intermediates were more reducible than dihaloarenes.
Aryl borates other than pinacolborate could be smoothly
generated by using the corresponding diboron esters (30−32,
Table 2B). However, B2(OH)4 was not compatible with our
method due to its insolubility in acetonitrile (33).
Table 2. Scope of Visible-Light-Induced Borylation of Aryl
Chlorides
a
A wide range of pharmaceutical compounds performed well
under a slightly modified borylation protocol by using DIPEA
as the electron donor, which possesses multiple Lewis basic
atoms and heterocyclic moieties that can potentially coordinate
and be problematic in transition metal catalysis (Table 2C).
Borylated derivatives of loratadine (34), meclizine (35),
indomethacin (36), carbinoxamine (37), chloropyramine
(38), cloperastine (39), chlorpromazine (40), and clofibrate
(41) were generated in moderate to good yields. Some of the
borylation products were isolated as organotrifluoroborate salts
as a part of the work-up procedure to assist product isolation.
Transformations Other than Borylation. The scope of
this carbazoyl dicyanobenzene-promoted ConPET strategy
could be extended to the formation of C−P bonds by
employing phosphines or phosphites as radical trapping agents.
Arylphosphonium salts are widely used as organocatalysts,
phase transfer reagents, ionic liquids, and so on. In addition,
they can also be used as functional handles for further C−O,
C−S, C−N, and C−C bond formation.42−45 However, existing
methods for the preparation of arylphosphonium salts from
aryl halides or pseudohalides rely on transition metal catalysis
and high-temperature processes.46−48 We herein developed a
metal-free synthesis of arylphosphonium salts under ambient
conditions using 3CzEPAIPN as the photocatalyst and
substoichiometric DIPEA as the electron donor (Figure 2A).
Notably, this reactivity enabled engagement of both electron-
rich and electron-poor aryl chlorides (42−51) as well as
various arylphosphines (52−54), delivering the desired
phosphonium salts in good to excellent yields. Moreover,
exposure of aryl exclusively in chlorides with trimethyl
a
Reaction conditions: aryl chloride (0.2 mmol), B2Pin2 (2.0 equiv), 4-
CN-Py (10 mol %), Na2C2O4 (1.5 equiv), K3PO4 (2.0 equiv), and
3CzEPAIPN (5 mol %) in MeCN (1 M) under irradiation with Kessil
light (456 nm, 2 × 40 W) at rt for 24 h under argon. Isolated yields.
b
c
See references in Table S6; potentials vs SCE. The reaction was
performed for 36 h. Only diborylation products were obtained.
e
Reaction conditions were slightly modified; see details in the
phosphite to slightly modified conditions enabled a visible
light promoted Arbuzov reaction for the generation of aryl
phosphonates (55−60, Figure 2B).49
The synthetic utility of this ConPET protocol was further
extended to dearomative hydroarylation of aryl chlorides to
produce spirocyclic cyclohexadienes (61−63), probably
through a reductive radical-polar crossover mechanism, as
reported by Jui50 (Figure 2C). The catalytic system could also
be applied to reductive defluorination of trifluoromethylarenes
to methylarenes (64, Figure 2D).51 Moreover, the developed
phosphorylation was amenable to scale-up with an operation-
ally simple continuous-flow setup, which resulted in
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J. Am. Chem. Soc. 2021, 143, 13266−13273