Organic Letters
Letter
transformation without the use of a directing group was
reported by Shi et al. (Scheme 1, b-2). They developed Ni-
catalyzed direct C−N borylation18 and arylation19 of tertiary
anilines. Direct C−N transformations have generally been
catalyzed by transition metal complexes via oxidative addition
of the C−N bonds to the metal center.20,21 However, metal-
free direct transformations of unreactive aromatic C−N bonds
are yet to be developed.
Based on the above research background, we focused on a
metal-free direct C−N borylation because it is a powerful
protocol for various organic syntheses. The resulting C−B
bonds can be transformed into diverse substituents and
functional groups.22 Metal-free radical borylation of aromatic
amines,23,24 including photoinduced reactions,8,25−28 have
recently been developed. However, the reactions generally
require stoichiometric amounts of additional reagents to
prepare the corresponding salts (Scheme 1, a-1). In this
study, we report the first example of a metal-free direct C−N
borylation of unreactive aromatic amines by a photocatalyst
under UV irradiation (Scheme 1c). In this reaction, readily
available pyrene served as a photocatalyst,29 and a significant
effect of CO2 on the efficient promotion of C−N borylation
was demonstrated.
in 80% yield in a slightly larger-scale reaction (entry 10). The
reaction conducted without the use of pyrene afforded 2a in
low yields in both the presence and absence of CO2 (entries 11
and 12).
Next, we investigated the substrate scope of the aromatic
amines using optimal reaction conditions (Scheme 2). To
Scheme 2. Direct Borylation of Aromatic Amines by
a
Cleavage of Unreactive C−N Bond
We began our investigation of direct C−N bond borylation
of N,N-dimethyl-4-biphenylamine (1a) with 2.0 equiv of
B2pin2 in the presence of 20 mol % of pyrene upon
photoirradiation at 365 nm under N2 atmosphere (Table 1).
a
Table 1. Optimization of Reaction Conditions
bc
,
c
entry
solvent
atmosphere
conv. (%)
yield (%)
1
2
3
4
5
6
7
8
9
CH2Cl2
DMF
MeCN
C6H6
N2 (close)
N2 (close)
N2 (close)
N2 (close)
N2 (close)
N2 (close)
N2 (close)
CO2 (close)
CO2 (balloon)
CO2 (balloon)
N2 (close)
CO2 (close)
37
49
68
59
80
71
85
90
97
90
13
15
0
0
0
a
b
B2pin2 (2.0 equiv). B2pin2 (3.0 equiv), pyrene (30 mol %), 36 h.
c
Isolated yield as pinacol ester without the treatment with KHF2 is
d
described in parentheses. 12 h.
50
58
66
67
82
93
88 (80)
13
15
THF
1,4-dioxane
CPME
CPME
CPME
CPME
CPME
CPME
simplify product purification, the resulting aryl boronic acid
pinacol esters were transformed to aryl trifluoroborates by
treating the reaction mixtures with KHF2. N,N-Dimethyl-4-
biphenylamines with an electron-donating substituent at the
para-position of the aniline ring were borylated to afford the
corresponding 4-biphenyltrifluoroborates 3b−3e in moderate
to excellent yields. The cyclopropyl group of 3d and the free
hydroxy group of 3e were tolerated under the reaction
conditions. Halogen atoms (F and Cl) were also left intact, and
the corresponding halo-4-biphenyltrifluoroborates 3f and 3g
were produced in high yields. Furthermore, the alkynyl group
was tolerated without dimerization or polymerization, and
product 3h was obtained in 72% yield. The trimethylsilyl group
was also tolerated under the reaction conditions, giving the
corresponding product 2i in 53% yield. 4-Mesityl-N,N-
dimethylaniline with fully twisted aromatic rings or N,N-
dimethyl-2-amine fluorene-fused aromatic rings were smoothly
converted to their corresponding 4-biphenyltrifluoroborate 3j
and fluorenyl trifluoroborate 3k in 78% yield and 81% yield,
respectively. The methoxycarbonyl group, which is an electron-
withdrawing group, was applied, and the corresponding
product 3l was obtained in 70% yield. In the case of
bis(dimethylamino)biphenyl, the C−N bond at the 4-position
d
e
10
11
12
f
f
a
1a (0.0600 mmol), B2pin2 (0.120 mmol), pyrene (0.0120 mmol),
CPME (0.60 mL). Conversion of 1a. Determined by GC. 1a (0.15
mmol), B2pin2 (0.300 mmol), pyrene (0.0300 mmol), CPME (1.5
mL). Isolated yield is described in parentheses. Without pyrene.
THF, tetrahydrofuran; DMF, dimethylformamide; CPME, cyclo-
pentyl methyl ether.
b
c
d
e
f
Solvent screening revealed that the desired 4-biphenylboronic
acid pinacol ester (2a) was not formed in CH2Cl2, DMF, or
MeCN (entries 1−3) but was formed in benzene and ethers
(entries 4−7). The best result was obtained with cyclopentyl
methyl ether (CPME), and the corresponding product 2a was
obtained in 67% yield (entry 7).30 Surprisingly, the CO2
atmosphere significantly improved the yield of 2a to 82%
(entry 8). Moreover, under the CO2 atmosphere in a balloon,
the yield of 2a reached 93% (entry 9). Product 2a was isolated
4775
Org. Lett. 2021, 23, 4774−4778