Organic Letters
Letter
research. Despondingly, when the reaction was conducted in
the presence of Pd(OAc)2 by using Na2CO3 as base, a stagnant
reaction was observed (Table 1, entry 1). To our delight, 9H-
Scheme 2. Substrate Scope with Respect to 2-
Iodobiphenyls
a
Table 1. Optimization of the Reaction Conditions
a
b
entry
ligand
base
solvent
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
CH3CN
1,4-dioxane
CHCl3
toluene
DMF
yield
1
2
3
4
5
6
7
8
9
10
--
PPh3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
K2CO3
K3PO4
NaOAc
Et3N
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
trace
13%
34%
10%
trace
73%
87%
69%
trace
n.r.
98%
81%
<10%
trace
n.r.
p-OMe(C6H4)3P
p-F(C6H4)3P
dppe
PCy3
PCy3
PCy3
PCy3
PCy3
PCy3
PCy3
PCy3
PCy3
PCy3
PCy3
PCy3
c
11
12
13
14
15
16
17
d
87%
38%
n.r.
e
DMF
DMF
f
18
PCy3
a
Reaction conditions: 0.2 mmol of 1a, 0.4 mmol of 2, 10 mol % of
Pd(OAc)2, 20 mol % of ligand, 2 equiv of base, 2 mL of solvent, at N2
b
c
d
for 8 h under 90 °C. Isolated yield. 3.0 equiv of K2CO3. 5 mol % of
e
f
Pd(OAc)2 + 10 mol % of PCy3. Air atmosphere. Without Pd(OAc)2.
fluoren-9-one 3a was achieved in 13% yield when triphenyl-
phosphine served as the additive. Since the ligand could
significantly enhance the reaction efficiency, we then
investigated a suite of different phosphine ligands (Table 1,
entries 2−6). Among the ligands inspected, tricyclohexylphos-
phine displayed the best catalytic partner, in which the desired
3a could be isolated in 73% yield (Table 1, entry 6).
Subsequently, a battery of bases were examined (Table 1,
entries 7−10). K3PO4, NaOAc, and Et3N were proved to be
inefficient or even ineffective. On the contrary, K2CO3 turned
out to be the optimum accelerant to deliver the 9H-fluoren-9-
one 3a in 87% yield (Table 1, entry 7). The augment of the
amount of K2CO3 was beneficial to this difluorocarbene
transfer reaction, and the yield of 3a could be increased to 98%
(Table 1, entry 11). As a follow-up optimization, we also
screened a range of solvents, and the results showed that DMF
was still the optimal reaction medium (Table 1, entries 12−
15). When the loading of catalyst was reduced, an inferior yield
of 3a was obtained (Table 1, entry 16). When the model
reaction was conducted under air atmosphere, the yield of 9H-
fluoren-9-one 3a was sharply decreased to 37% (Table 1, entry
17). The control experiment indicated that Pd(OAc)2 was
indispensable for this transformation (Table 1, entry 18).
With the optimized reaction conditions in hand, the
substrate scope of this novel Pd-catalyzed assembly of
fluoren-9-ones was then investigated (Scheme 2). The
electronic effect of the substituents installed on 2-iodinebi-
a
All reactions unless otherwise stated were carried out with 1 (0.2
mmol), 2 (0.4 mmol), Pd(OAc)2 (10 mol %), PCy3 (20 mol %), and
K2CO3 (3.0 equiv) in DMF (2 mL) under N2 at 90 °C for 8 h.
phenyls had no evident distinctions. Regardless of the 2-
iodinebiphenyls bearing the electron-withdrawing or electron-
donating groups on the aromatic ring, the 2-iodinebiphenyls
can almost be converted equivalently, enabling the formation
of the corresponding substituted fluorenones in excellent yields
(3a−3t). The structure of 3a was definitely confirmed by X-ray
single-crystal diffraction. It should be noted that a succession
of sensitive functional groups, such as chlorine, formyl, ketone,
ester, TMS, and vinyl, were well amenable to this Pd-catalyzed
C−H activation, which makes the further structural elaboration
of the fluoren-9-ones readily available. In addition to para-
substituted 2-iodinebiphenyls, meta- and ortho-substituted 2-
iodinebiphenyls were also compatible in this Pd-catalyzed
difluorocarbene transfer reaction. The targeted products (3m−
3o) were obtained in 93%−99% yields. A range of 2-
iodinebiphenyls with different substituents installed on the
ring of iodobenzene were also certified to be good candidates
to assemble the fluorenones (3p−3t) in 93%−98% yields.
Gladly, the subjection of fused 2-iodinebiaryls to this
2544
Org. Lett. 2021, 23, 2543−2547