1141
Table 2. Addition of various ketimines to styrene 2aa
Table 3. Addition of ketimine 1a to various styrene deriva-
tivesa
CoBr2 (5 mol%)
P(4-FC6H4)3 (10 mol%)
CyMgBr (50 mol%)
PMP
N
R2
O
R2
CoBr2 (5 mol%)
P(4-FC6H4)3 (10 mol%)
CyMgBr (50 mol%)
PMP
N
H+
O
+
H+
Ph
Ph
THF, rt, 12–24 h
+
THF, rt, 24 h
R1
R1
O
1a-1m
2a
3aa-3ma
R
R
1a
2b-2l
3ab-3al
3aa (R = H), 90% (97/3)
3ba (R = Ph), 80% (99/1)
3ca (R = OMe), 90% (97/3)
3da (R = Cl), 86% (92/8)
3ea (R = F), 75% (91/9)
3fa (R = CF3), 60% (80/20)b
O
O
O
Ph
Ph
Me
3ag, 90% (93/7)
F
R
R
3ga, 66% (99/1)
3ab (R = OMe), 75% (92/8)
3ac (R = F), 55% (90/10)
3ad (R = Cl), 15% (91/9)b
O
R
O
O
O
Ph
3ae (R = SiMe3), 70% (>99/1)
3af (R = NPh2), 58% (95/5)c
3ah (R = Me), 35% (67/33)
3ai (R = OMe), 80% (>99/1)
Ph
Ph
O
Me
O
O
O
O
3ha, 78% (94/6)
3ia, 70% (>99/1)c
3ja, 92% (99/1)
OMe
OMe
Ph
O
O
O
O
O
OMe
Ph
N
Ph
3aj, 83% (96/4)
3ak, 84% (>99/1)
3al, 43% (>99/1)
O
Me
3ka, 77% (92/8)d
3la, 83% (>99/1)
3ma, 56% (>99/1)e
aThe reaction was performed on a 0.3 mmol scale. The yield
refers to the isolated yield. The b/l ratio determined by
1H NMR is shown in parentheses. See Supporting Information
for experimental details.15 bObtained as a mixture with
dechlorinated product (i.e., 3aa, ratio = 10:1). 100 mol % of
CyMgBr was used.
aThe reaction was performed on a 0.3 mmol scale. The yield
refers to the isolated yield. The b/l ratio determined by
1H NMR is shown in parentheses. See Supporting Information
for experimental details.15 bThe reaction was performed using
P(p-Tol)3 and Me3SiCH2MgCl instead of P(4-FC6H4)3 and
c
c
CyMgBr, respectively, for 48 h. The reaction time was 36 h.
dThe b/l ratio was determined by GC. The reaction time was
e
exclusively affording the corresponding branched adducts in 79
and 72% yields, respectively (data not shown).
28 h.
The scope of styrene derivatives was next explored
(Table 3). Styrenes bearing para-methoxy, -fluoro, -trimethyl-
silyl, and -diphenylamino groups participated in the reaction
with imine 1a to afford the corresponding branched adducts in
moderate-to-good yield (3ab, 3ac, 3ae, and 3af). In contrast, p-
chlorostyrene reacted sluggishly to afford the adduct 3ad in poor
yield, which was accompanied by a small amount of dechlori-
nation product (i.e., 3aa). An ortho-methyl group on styrene
made the reaction rather sluggish and significantly reduced the
regioselectivity (3ah), while o-methoxystyrene smoothly par-
ticipated in the reaction to afford the adduct 3ai with perfect
regioselectivity. Polyalkoxystyrenes and 2-vinylnaphthalene
also afforded the desired branched adducts 3aj-3al with
excellent regioselectivity. Note that the present catalytic system
also allowed (linear) for the ortho-alkylation of 1a with
vinyltrimethylsilane, norbornene, and n-hexene, albeit in a low
yield for the last case (75, 91, and 15% yields, respectively; data
not shown).18
The present hydroarylation reaction is scalable enough to
allow for further transformation of the 1,1-diarylethane product
(Scheme 2). The reaction of 1a and 2a could be performed on
a 10 mmol scale with virtually no decrease in the yield and
regioselectivity. Reductive amination of the acetyl group of the
hydroarylation product 3aa with piperidine afforded the product
4 in 70% yield (as a 1:1 mixture of diastereomers), which is
among a series of related compounds with potential serotonin
releasing activity.19 The diarylethane 3aa was also amenable to
With the CoBr2-P(4-FC6H4)3-CyMgBr catalytic system in
hand,14 we first explored the reaction of a variety of aryl
ketimines with styrene (Table 2). Imines bearing electron-
donating and neutral substituents at the para-position afforded
the desired products in good yield with high branched selectivity
(3aa-3ca). On the other hand, para-chloro and -fluoro sub-
stituents slightly lowered the regioselectivity (3da and 3ea). A
para-trifluoromethyl group made the reaction under the standard
conditions rather sluggish, presumably because it slowed the
reductive elimination step.10a Reasonable conversion was
achieved by changing the ligand and the Grignard reagent to
P(p-Tol)3 and Me3SiCH2MgCl, respectively, albeit with much
reduced regioselectivity (3fa). As has been observed for other
cobalt-catalyzed C-H functionalization reactions,10b,16,17 the
fluorine atom and methylenedioxy group at the meta-position
directed the reaction to take place at their proximal positions
(3ga and 3ha), while an imine bearing a meta-methyl group
expectedly reacted at the less hindered position (3ia). Imines
derived from propiophenone and tetralone smoothly participated
in the reaction to afford the corresponding adducts 3ja and 3ka
in good yield with high branched selectivity. Heteroaryl imines
were also amenable to the present hydroarylation reaction, as
demonstrated by the formation of functionalized indole 3la and
benzofuran 3ma with perfect (>99/1) regioselectivity. Note that
the present catalytic system was also applicable to aromatic
aldimines derived from 1-naphthaldehyde and o-tolualdehyde,
Chem. Lett. 2013, 42, 1140-1142
© 2013 The Chemical Society of Japan
Dong, Jinghua
