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T. Hou et al. / Tetrahedron Letters 57 (2016) 2273–2276
Table 1
Br
NR2
Ir(dtb-bpy)(ppy)2PF6 (1 mol%)
Optimization of the reaction conditionsa
CBr4 (1.5 equiv.)
amines
hv, CH2Cl2
Br
photocatalyst (1 mol%)
bromine source (1.5 equiv.)
1a
2a
morphline: 3a 90%
piperidine:
pyrrolidine:
4
5
85%
70%
hv, solvent
n-heptamine: 6 65%
1a
2a
Scheme 1. One-pot benzylic C–N bond formation.
Entry
Catalyst
Bromine source
Solvent
Yield
1
2
3
4
5
6
7
8
[Ir(ppy)2(dtb-bpy)]PF6
Ir(ppy)3
Ru(bpy)3(PF6)2
FIrpic
Rose Bengal
[Ir(ppy)2(dtb-bpy)]PF6
[Ir(ppy)2(dtb-bpy)]PF6
[Ir(ppy)2(dtb-bpy)]PF6
[Ir(ppy)2(dtb-bpy)]PF6
[Ir(ppy)2(dtb-bpy)]PF6
[Ir(ppy)2(dtb-bpy)]PF6
—
CBr4
CBr4
CBr4
CBr4
CBr4
CBr4
CBr4
CBrCl3
TBAB
CBr4
CBr4
CBr4
CBr4
CBr4
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
MeCN
CHCl3
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
42%
N.R.
N.R.
N.R.
Trace
8%
49%
41%
N.R.
12%b
26%c
N.R.
N.R.d
99%e
Table 2
Screening of substitution on the alkyl group of ethylbenzenea,b
O
N
Br
Ir(dtb-bpy)(ppy)2PF6 (1 mol%)
morpholine (20 equiv.)
R
R
CBr4 (1.5 equiv.)
R
9
hv, CH2Cl2
10
11
12
13
14
1
2
3
[Ir(ppy)2(dtb-bpy)]PF6
[Ir(ppy)2(dtb-bpy)]PF6
O
O
N
O
N
N
a
Reactions were performed with 1a (0.5 mmol), bromine source (0.75 mmol)
Ph
Ph
3c
Ph
3a
and catalyst (1 mol %) in a solvent (2 mL) under N2 atmosphere, irradiated under a
14 W CFL for 12 h. Yields were determined by GC.
a
c
, 90%
O
3b,70%c
, 82%
b
The reaction was conducted under an O2 balloon.
The reaction was conducted under an air balloon.
Reaction was conducted without light irradiation.
O
O
c
d
N
N
N
e
OMe
Reacted for 36 h.
Ph
3d, 35%d
OEt
Ph
Ph
OMe
3f, 67%d
d
3e
, 37%
O
O
O
(Table 1, entry 1). The desired product was formed in 42% yield
without the observation of dibrominated side product. This result
encouraged us to optimize the reaction conditions further. First, a
number of photocatalysts were screened. However, other iridium
complexes such as FIrpic and Ir(ppy)3, as well as ruthenium com-
plex Ru(bpy)3Cl2 were ineffective for this transformation (Table 1,
entries 2–4). Organic dye, Rose Bengal, could only afford trace of
the product (Table 1, entry 5). Various solvents were next exam-
ined. Acetonitrile afforded the desired product only in 8% yield
(Table 1, entry 6). The reaction in CHCl3 was as good as that in
CH2Cl2. The desired product was formed in 49% after 12 h in CHCl3
(Table 1, entry 7). Other bromine sources were also investigated.
CBrCl3 gave 41% yield while tetrabutylammonium bromide
afforded no product (Table 1, entry 8 and entry 9). When the reac-
tion was exposed to air or oxygen, a major side product, 2-bromo-
1-phenyethanone, was formed, which significantly lowered the
yields of the desired product (Table 1, entry 10 and entry 11).
The reaction was completely stopped in the absence of either cat-
alyst or visible light irradiation, showing that it was a visible-light-
promoted reaction (Table 1, entry 12 and entry 13). Since about
half of the ethylbenzene remained after 12 h of visible light irradi-
ation, the reaction time was prolonged to 36 h. The reaction went
to completion, and (1-bromoethyl)benzene was formed in 99%
yield (Table 1, entry 14).
With the optimized conditions in hand, we started to test the
substrate scope of the reaction. The products were found to be very
difficult to purify by column chromatography because of low
polarity. It was decided to convert the benzyl bromide product to
more polar product through nucleophilic substitution reaction. A
sequential one-pot reaction was achieved by adding amines after
the completion of photoredox bromination reaction. Clean conver-
sion of benzyl bromide to the corresponding amines was obtained.
Morpholine, piperidine, pyrrolidine, and n-heptamine were all
used to afford the desired amines in good isolated yields
(Scheme 1).
N
N
N
OCOCH3
COOEt
Ph
Ph
Ph
OCOCH3
3g, 55%d
d
d
3h
, 47%
3i
, 61%
a
Reaction conditions: substrate 1 (0.5 mmol), Ir(dtb-bpy)(ppy)2PF6 (1 mol %) and
CBr4 (0.75 mmol), in CH2Cl2 (2 mL), irradiated under 14 W CFL for 36 h. After
reaction completed, morpholine (10.0 mmol) was added into the mixture and
stirred for 8 h.
b
Isolated yield.
Reacted for 48 h.
c
d
Reacted for 72 h, CBrCl3 was used as the bromine source.
length of the aliphatic carbon chain to three or five carbons gave
70% and 82% yields of the corresponding products, respectively
(Table 2, entries 3b and 3c). Functional group tolerance on the
aliphatic chain was tested. Both (3-ethoxypropyl)benzene and
(3-methoxypropyl)benzene provided the desired products in low
yields (35% and 37%, respectively. Table 2, entries 3d and 3e).
Extending the carbon chain to three carbons increased the yield
to 65% (Table 2, entry 3f), probably due to the diminished elec-
tron-withdrawing induction effect of the alkoxy group. The trend
was reverted when the alkoxy groups were replaced by esters.
Compounds 3g and 3h were obtained in 55% and 47% yields,
respectively. In the case of 3i, the yield of the desired product
was 61%. The results showed that many functional groups were
tolerated, but the substitution groups on the alkyl chain had a pro-
found influence on the reaction.
Various substituents on the benzene ring of the ethylbenzene
were then explored. Substrates bearing halogens at different
positions of the benzene ring were examined. Para-, meta-, and
ortho-bromo ethylbenzenes afforded the corresponding products
in 91%, 80%, and 92% isolated yields, respectively (Table 3,
entries 3j–3l). para-Ethyl iodobenzene gave 60% of the corre-
sponding benzyl amine product (Table 3, entry 3m). para-Methyl
ethylbenzene was only monobrominated at the methylene posi-
tion with 63% isolated yield (Table 3, entry 3n). No bromination
The model substrate, ethylbenzene, afforded the product 3a in
excellent isolated yield (90%, Table 1, entry 3a). Prolonging the