Communication
Table 1. Optimization of the reaction conditions.[a]
Table 3. Substrate scope.[a]
Entry
Precursor
L*
Yield [%]
ee [%]
Entry
R
R’ Ar
Yield [%]
ee [%]
1
2
3
4
5
6
7[b]
8
[Rh(nbd)2](ClO4)
[Rh(nbd)2](BF4)
[Rh(nbd)2](PF6)
[Rh(nbd)2](SbF6)
[Rh(nbd)2](NTf2)
Rh(acac)(coe)2
[Rh(nbd)2](BF4)
[Rh(nbd)2](BF4)
[Rh(nbd)2](BF4)
[Rh(nbd)2](BF4)
[Rh(nbd)2](BF4)
(R,R)-N-Me-BIPAM
(R,R)-N-Me-BIPAM
(R,R)-N-Me-BIPAM
(R,R)-N-Me-BIPAM
(R,R)-N-Me-BIPAM
(R,R)-N-Me-BIPAM
(R,R)-N-Me-BIPAM
(R,R)-Me-BIPAM
(R,R)-S-Me-BIPAM
(R)-BINAP
69
73
71
71
66
60
81
48
45
n.r.
28
98
99
99
97
98
97
98
68
86
–
1
2
3
4
PhCH2CH2 (1a) Ts C6H5 (2a)
81 (3aa)
76 (3ba)
58 (3ga)
63 (3ha)
74 (3ia)
66 (3ja)
79 (3ka)
77 (3la)
79 (3ab)
81 (3ac)
66 (3ad)
70 (3ae)
61 (3af)
74 (3ag)
98
96
96
95
97
94
97
95
93
89
96
97
89
86
Et (1b)
Ts C6H5 (2a)
Ts C6H5 (2a)
Ts C6H5 (2a)
Ts C6H5 (2a)
Ts C6H5 (2a)
Ns C6H5 (2a)
Ns C6H5 (2a)
Me (1g)
n-Pent (1h)
iBu (1i)
iPr (1j)
iPr (1k)
Cy (1l)
5
6[b]
7
8
9
9
10
11
PhCH2CH2 (1a) Ts 4-MeOC6H4 (2b)
PhCH2CH2 (1a) Ts 4-PhOC6H4 (2c)
PhCH2CH2 (1a) Ts 4-MeSC6H4 (2d)
PhCH2CH2 (1a) Ts 4-MeC6H4 (2e)
PhCH2CH2 (1a) Ts 4-HOC6H4 (2 f)
PhCH2CH2 (1a) Ts 4-PhC6H4 (2g)
PhCH2CH2 (1a) Ts 4-ClC6H4 (2h)
PhCH2CH2 (1a) Ts 4-BrC6H4 (2i)
PhCH2CH2 (1a) Ts 4-FC6H4 (2j)
PhCH2CH2 (1a) Ts 4-CF3OC6H4 (2k)
PhCH2CH2 (1a) Ts 4-CF3C6H4 (2l)
10
11
12
13
14
15
16[c]
17[c]
18[c]
19[c]
20
21
22
23
(R)-monophos
7
[a] Reaction conditions: 1a (0.5 mmol), 2a (1.5 equiv), rhodium cat.
(3 mol%), and (R,R)-N-Me-BIPAM (1.1 equiv to Rh) in DME (2 mL) was
stirred for 16 h at 508C. [b] The reaction was conducted at 808C.
56 (57[c]) (3ah) 69 (97[c])
59 (3ai)
49 (3aj)
65 (3ak)
47 (3al)
97
96
92
92
97
78
88
99
a moderate yield was obtained in the case of Me-BIPAM or S-
Me-BIPAM (entries 8 and 9). Other typical asymmetric ligands,
such as 2,2’-bis(diphenylphosphino)-1,1’-binaphthyl (BINAP) or
Monophos, gave the corresponding product in low yields (en-
tries 10 and 11). Unfortunately, under our reaction conditions,
aldimine 1a decomposed to give an alcohol as a byproduct by
arylation of aldehydes in all cases.
PhCH2CH2 (1a) Ts 3-MeOC6H4 (2m) 74 (3am)
PhCH2CH2 (1a) Ts 2-MeOC6H4 (2n)
PhCH2CH2 (1a) Ts 2-naphthyl (2o)
59 (3an)
76 (3ao)
PhCH2CH2 (1a) Ts 3,5-MeOC6H3 (2p) 70 (3ap)
[a] Reaction conditions:
1
(0.5 mmol),
2
(1.5 equiv), rhodium cat. (3
mol%), and (R,R)-N-Me-BIPAM (1.1 equiv to Rh) in DME (2 mL) was stirred
for 16 h at 808C. [b] Reaction was conducted at 508C. [c] [Rh(acac)(coe)2]
(3 mol%) was used instead of [Rh(nbd)2]BF4.
We also examined arylation of substrates bearing various
protecting groups on the nitrogen atom of imine (Table 2). The
The reaction of the simplest substrate 1g showed a high enan-
tioselectivity to give 3ga in 58% yield with 96% ee, a high
enantioselectivity that has never been achieved by catalytic ar-
ylation (Table 3, entry 3). Although some catalytic systems are
known to promote asymmetric arylation of alkyl aldimines,
there is only one report for the arylation of 1g with insufficient
results,[5d] despite their structural potential including the NPS R-
568 and Cinacalcet. When the R group was changed from
methyl to other primary alkyl groups, the reactions also pro-
ceeded smoothly to afford the corresponding chiral products
in good yields and with high enantioselectivities (entries 4 and
5). Substrates possessing a substituent at the a-position effec-
tively underwent arylation to give products with high enantio-
selectivities (entries 6–8). In the case of these imines, Ns-aldi-
mine was more suitable than Ts-aldimine (entries 7 and 8).
Next, asymmetric arylation of 1a with various arylboronic acids
was examined under optimized conditions (entries 9–23). Aryl-
boronic acid containing an electron-donating group could be
effectively added to imine 1a with good to high enantioselec-
tivities (entries 9–13). It is noteworthy that a non-protected hy-
droxyl group did not affect the reaction (entry 13). However,
a strongly electron-deficient substituent, such as a Cl, Br, F, or
a OCF3 or CF3 group reduced the reactivity of the substrate
(entries 15–19). In these reactions, [Rh(acac)(coe)2] (acac=acet-
ylacetonate; coe=cyclooctene) showed higher enantioselectiv-
ities than [Rh(nbd)2](BF4). Arylboronic acids 2m–p were also
Table 2. Optimization of the protecting group of imines.[a]
Entry
PG
Yield [%]
ee [%]
1
2
3
4
5
Ts (1b)
Ns (1c)
Bn (1d)
Boc (1e)
OBn (1 f)
76 (3ba)
73 (3ca)
n.r. (3da)
n.r. (3ea)
n.r. (3 fa)
96
97
–
–
–
[a] Reaction conditions:
1 (0.5 mmol), 2a (1.5 equiv), rhodium cat.
(3 mol%), and (R,R)-N-Me-BIPAM (1.1 equiv to Rh) in DME (2 mL) was
stirred for 16 h at 808C.
type of protecting group of imines noticeably affected the re-
activity, and no reaction occurred when N-Bn (1d), N-Boc (1e)
(Boc=tert-butoxycarbonyl), and N-OBn (1 f) aldimines were
used as substrates because of the instability or low electrophi-
licity of imines. According to the results of the screening, N-sul-
fonyl-type aldimines, such as Ts (1b) and Ns (1c), are most ef-
fective in our developed catalytic arylation.
With the optimized reaction conditions in hand, various aldi-
mine substrates and boronic acids were examined (Table 3).
Chem. Eur. J. 2016, 22, 7739 – 7742
7740
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