Angewandte
Chemie
À
dine dearomatization processes that involve C N bond
which features a larger bite angle, was used as part of the
activation.[7]
catalyst system, product 2a was obtained in 59% yield.
Moreover, further increasing the steric bulk and bite angle of
the phosphine ligand by using Xantphos led to a substantial
increase in catalytic activity, and the desired carbonylation
product 2a was isolated in 81% yield (entry 12). When
NiXantphos, with a very similar bite angle, was used, the
desired product was formed in an almost identical yield. The
exceptionally high reactivity of the Xantphos-containing
catalyst might be due to the unique structure of the ligand,
which is capable of forming both cis and trans Pd complexes,
thus facilitating the catalytic process. The huge bite angle of
154.788 can be clearly seen in the X-ray structure of
[Pd(Xantphos)I2].[10] Screening some representative solvents
revealed that the reaction was most efficient in toluene, in
which the desired product 2a was obtained in good yield
(entry 12). The reaction reached completion in one hour to
yield the corresponding product in 87% yield (entry 20).
With optimized reaction conditions in hand, substrates
with various leaving groups were subjected to the standard
conditions. As summarized in Table 2, substrates containing
Our investigations began with the direct cyclocarbonyla-
tion of N,N-diisopropyl-3-(pyridin-2-yl)prop-2-en-1-amine
(1a) in toluene by palladium catalysis under CO atmosphere
at 1208C (Table 1). After an extensive screening of catalysts,
Table 1: Optimization of the reaction conditions.[a]
Entry
[Pd]
Ligand
Solvent
Yield[b] [%]
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20[c]
21
PdCl2
PdBr2
PdI2
[Pd(cod)I2]
[Pd(CH3CN)2Cl2]
[{Pd(allyl)Cl}2]
PdI2
PdI2
PdI2
PdI2
PdI2
PdI2
PdI2
PdI2
PdI2
PdI2
PdI2
–
–
–
–
–
–
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
xylene
<5
14
67
63
<5
<5
<5
<5
59
<5
<5
84 (81)
83
DPPE
DPPP
DPPB
DPPF
BINAP
Xantphos
NiXantphos
DPEphos
Xantphos
Xantphos
Xantphos
Xantphos
Xantphos
Xantphos
–
Table 2: Influence of the leaving group.[a]
42
83
82
84
80
70
91 (87)
0
mesitylene
benzene
PhCF3
NMP
toluene
toluene
Entry
Substrate
X
Yield[b] [%]
1 h
91
80
81
<5
<5
<5
<5
<5
24 h
PdI2
PdI2
PdI2
–
1
2
3
4
5
6
7
8
1a
1b
1c
1d
1e
1 f
N(iPr)2
NEt2
N(Cy)2
NPh2
NBn2
OH
–
–
–
16
55
15
73
13
[a] Reaction conditions: 1a (0.5 mmol), [Pd] (0.025 mmol), ligand
(0.03 mmol), solvent (2 mL), CO (10 atm), 1208C, 24 h. [b] Yields were
determined by GC analysis using n-hexadecane as an internal standard;
yields of isolated products are given in parentheses. [c] One hour.
BINAP=2,2’-bis(diphenylphosphino)-1,1’-binaphthyl, DPEphos=bis[2-
(diphenylphosphino)phenyl] ether, DPPB=1,4-bis(diphenylphosphino)-
butane, DPPE=1,2-bis(diphenylphosphino)ethane, DPPF=1,1’-bis(di-
phenylphosphino)ferrocene, DPPP=1,3-bis(diphenylphosphino)pro-
pane, NiXantphos=4,6-bis(diphenylphosphino)phenoxazine, Xant-
phos=4,5-bis(diphenylphosphino)-9,9-dimethylxanthene.
1g
1h
OAc
Cl
[a] Reaction conditions: 1 (0.5 mmol), PdI2 (0.025 mmol), Xantphos
(0.03 mmol), solvent (2 mL), CO (10 atm), 1208C. [b] Yields were
determined by GC analysis using n-hexadecane as an internal standard.
Bn=benzyl, Cy =cyclohexyl.
to our great delight, the desired product 2a was obtained in
67% yield in the presence of a catalytic amount of PdI2
(5 mol%) and CO (10 atm). [Pd(cod)I2] was also an effective
catalyst of this reaction, giving the carbonylation product in
63% yield. As expected, no carbonylation took place without
a catalyst (entry 21), and representative palladium catalysts,
such as PdCl2, PdBr2, [Pd(CH3CN)2Cl2], and [{Pd(allyl)Cl}2],
were not effective (entries 1, 2, 5, and 6). Inspired by this
promising lead, we next sought to improve the efficiency of
the reaction. Various phosphine ligands were then screened in
combination with PdI2 as the catalyst precursor, and the
transformation was found to be sensitive to the bite angle of
the bis(phosphine) ligand (entries 7–14).[9] Catalysts derived
from bis(diphenylphosphino)-type ligands, such as DPPE,
DPPP, DPPF, or BINAP, resulted in low conversion into the
desired product based on GC analysis. However, when DPPB,
different leaving groups (1a–1h) gave the desired product in
distinctly different yields. For allylamines with N(iPr)2, NEt2,
or N(Cy)2 as the leaving group, the cycloadduct 2a could be
obtained in high yields even in one hour (entries 1–3).
However, when other leaving groups, such as NPh2, NBn2,
OH, OAc, or Cl, were installed in the allylic skeleton, the
conversion was dramatically lower under identical reaction
conditions (entries 4–8). The lower activity of these substrates
might be attributed to either the difficult cleavage of the
À
corresponding C X bonds or their reluctance to undergo
a late-stage Heck reaction.[11]
On the basis of the results described above, a variety of
azaarene-substituted allylamines with N(iPr)2 as the leaving
group were submitted to the Pd-catalyzed dearomative
cyclocarbonylation reaction to investigate its substrate scope
and generality (Table 3). A series of substituents on the
Angew. Chem. Int. Ed. 2015, 54, 10912 –10916
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim