Chiral P-containing palladacycle-catalyzed asymmetric ring-opening reactions of oxabicyclic alkenes with alkenyl boronic acids

Article abstract of DOI:10.1055/s-0030-1259716

An efficient palladacycle-catalyzed asymmetric ring-opening reaction of oxabicyclic alkenes with alkenyl boronic acids was developed to afford the corresponding products in good to excellent yields and enantioselectivity. Georg Thieme Verlag Stuttgart · New York.

Full text of DOI:10.1055/s-0030-1259716

LETTER
943
Chiral P-Containing Palladacycle-Catalyzed Asymmetric Ring-Opening
Reactions of Oxabicyclic Alkenes with Alkenyl Boronic Acids
R
ing-Opening Re
a
i
ctions
a
y
o
clic Alkenes
-
w
ith Alk
J
enyl Bor
o
u
nic Acids n Huang, Dong-Liang Mo, Chang-Hua Ding, Xue-Long Hou*
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences,
345 Lingling Road, Shanghai 200032, P. R. of China
Fax +86(21)54925100; E-mail: xlhou@sioc.ac.cn
Received 9 December 2010
Dedicated to Professors Xi-Yan Lu and Li-Xin Dai
ee. Encouraged by this result, a series of P-containing and
N-containing palladacycles were examined under the con-
ditions shown in Scheme 1. It can be found from Table 1
that P-containing palladacycle 5 led to the product in high
yield,13 while the enantioselectivity dropped to 8% ee (en-
try 2, Table 1). Chiral phosphapalladacycle 6 was also
tested, but it could not catalyze the reaction effectively
(entry 3, Table 1). Meanwhile, all N-containing pallada-
cycles screened afforded the corresponding product in
trace amounts (entries 4–6, Table 1), which suggested that
the presence of a P atom coordinated to a Pd atom should
be important on the catalytic activity of palladacycles in
the present reaction. With palladacycle 4, the solvent ef-
fect on the reaction was also evaluated. We can see that
the reaction proceeded smoothly to give the product in
Abstract: An efficient palladacycle-catalyzed asymmetric ring-
opening reaction of oxabicyclic alkenes with alkenyl boronic acids
was developed to afford the corresponding products in good to ex-
cellent yields and enantioselectivity.
Key words: palladacycle, asymmetric catalysis, ring-opening reac-
tion, oxabicyclic alkenes, alkenyl boronic acids.
The past two decades have witnessed significant develop-
ment in palladacycle chemistry.1 The palladacycles have
found their wide applications in a variety of fields such as
biological chemistry,2 material science,3 organic synthe-
sis,4 and ligand resolution.5,7a Palladacycles have also
been used as catalyst in asymmetric catalysis,6,7b–d,8 how-
ever, in most of these cases, palladacycles serve as Lewis
acids. In addition, racemic products were obtained in
some cases,7e,f,9 despite chiral palladacycles were used.
O
OH
On the other hand, transition-metal-catalyzed ring-open-
ing reactions of oxabicyclic alkenes have become a useful
tool for the synthesis of biologically active molecules10
and polymer components.11 Many efficient enantioselec-
tive transformations involving the oxabicyclic alkenes
were reported to afford hydroxy-dihydronapthalene
cores.12 We recently found that palladacycle should be the
real catalyst in the ring-opening reactions of oxabicyclic
alkenes with organozinc halides,9 and realized an asym-
metric ring-opening reaction of oxabicyclic alkenes with
aryl boronic acids using chiral phosphorus-containing
palladacycle as catalyst.7b As our continuing efforts to
explore the asymmetric catalysis by means of chiral palla-
dacycles, we describe herein chiral P-containing pallada-
cycle-catalyzed ring-opening reactions of oxabicyclic
alkenes with alkenyl boronic acids. The newly incorporat-
ed C–C double bond from alkenyl boronic acids enables
the resulted products flexible for further elaboration.
n-hexyl
1a
+
palladacycle (5 mol%)
base in H2O
(HO)2B
(5 M, 0.5 equiv)
solvent, 0 °C
n-hexyl
3a
2a
Cl
Cy
Pd
P
OAc
2
Cy
Pd
PPh2
Fe
4
5
O
O
O
N
P
Pd
Pd
O
Br
Cl
2
2
We commenced our study by treatment of 7-oxabicycle
alkene 1a with (E)-oct-1-enylboronic acid (2a) in dichlo-
romethane at 0 °C in the presence of palladacycle 4 and
Cs2CO3 according to our previous work.7b To our delight,
the reaction proceeded smoothly, and the desired ring-
opening product 3a was obtained in 75% yield with 76%
7
6
O
O
O
N
N
N
Pd
Br
Pd
Ph3P
Br
8
9
SYNLETT 2011, No. 7, pp 0943–0946
x
x.
x
x.
2
0
1
1
Advanced online publication: 10.03.2011
DOI: 10.1055/s-0030-1259716; Art ID: W33710ST
Scheme 1
© Georg Thieme Verlag Stuttgart · New York

944
X.-J. Huang et al.
LETTER
moderate to good yields and enantioselectivities in vari- Table 2. It can be seen that a wide range of oxabicyclic
ous nonprotic solvents (entries 7–13, Table 1). The best alkenes 1 and alkenyl boronic acids 2 are suitable sub-
solvent was still dichloromethane in terms of both yield strates for the reaction, affording ring-opening products 3
and enantioselectivity (entry 1, Table 1). The protic sol- in good to excellent yields with 53–97% ee. The length of
vent has detrimental effect to the reaction. When MeOH the chain has a slight effect on the enantioselectivity when
was used only 24% yield of 3a was obtained accompany- substituents of alkenyl were linear alkyl groups (entries 1–
ing 57% yield of the side product resulted from dehydra- 4, Table 2). The incorporation of bulkier group into alke-
tion of ring-opening product 3a (entry 14, Table 1).
nyl boronic acid led to the significant effect on stereo-
chemistry of the reaction. The enantioselectivity
decreased to 66% ee for boronic acid 2e with cyclohexyl
group, although the yield was as high as 93% (entry 5,
Table 2). It is noteworthy that the excellent enantioselec-
tivity (over 89%) was obtained in case of alkenyl boronic
acid with tert-butyl substituent (entries 6, 9, and 12,
Table 2), especially, 97% ee was achieved when it was
treated with substrate 1e (entry 12, Table 2). The same
trend was observed for oxabicyclic alkene 1b (entries 7–
9, Table 2). Substituent on the oxabicyclic alkene has a
negative effect on the reaction. Neither the presence of
electron-donating groups nor electron-withdrawing
groups could increase the enantioselectivity (entries 7, 10,
and 11, Table 2).
Table 1 Optimization of Reaction Conditions for the Reaction
Shown in Scheme 1a
Entry Palladacycle Solvent
Base
Yield (%)b ee (%)c
1
2
4
5
6
7
8
9
4
4
4
4
4
4
4
4
4
4
4
4
4
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
DME
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
CsF
75
76
8
66
d
3
trace
trace
trace
trace
52
–
d
4
–
d
5
–
d
6
–
7
70
72
66
75
70
71
74
76
81
80
74
Table 2 Substrate Scopea
8
Et2O
77
R2
OH
(HO)2B
R3
R1
R1
R3
9
MeCN
DCE
56
palladacycle 4
2
CsF in H2O (5 M)
CH2Cl2, 0 °C
10
11
12
13
14
15
16
17
18
19
62
+
R2
R2
THF
62
3
R1
R1
1a R1 = R2 = H
1b R1 = Me; R2 = H
1c R1 = H; R2 = OMe
1d R1 = F; R2 = H
1e R1 = Br; R2 = H
toluene
CHCl3
MeOH
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
65
O
63
R2
1
24
Entry
1
1
2 R3
Yield of 3 (%)b ee (%)c
93
1a
1a
1a
1a
1a
1a
1b
1b
1b
1c
1d
1e
2a n-hexyl
2b n-pentyl
2c n-Bu
2d n-Pr
2e Cy
3a 93
3b 94
3c 92
3d 95
3e 93
3f 80
3g 82
3h 87
3i 72
3j 78
3k 85
3l 70
81
76
75
78
66
91
79
68
89
53
70
97
K3PO4
KF
86
2
94
316
4
d
K2CO3
Na2CO3
trace
trace
–
d
–
a Molar ratio of 1a/2a/palladacycle/base = 1:1.5:0.05:0.5.
b Isolated yield.
5
c Determined by chiral HPLC.
6
2f t-Bu
d Starting material was recovered in >90%.
7
2a n-hexyl
2e Cy
8
Next, the impact of bases was investigated to improve the
efficiency of the reaction (entries 15–19, Table 1) as the
base usually plays an important role in the reaction in-
volving boronic reagent.14 CsF was proved to be a better
base than Cs2CO3, K3PO4, and KF, providing the product
3a in 93% yield and 81% ee (entry 15 vs. entries 1, 16, and
17, Table 1). The reaction proceeded barely when the
weak bases such as K2CO3 and Na2CO3 were used (entries
18 and 19, Table 1).
9
2f t-Bu
10
11
12
2a n-hexyl
2a n-hexyl
2f t-Bu
a Molar ratio of 1/2/4/CsF = 1:1.5:0.05:0.5.
b Isolated yields.
c Determined by chiral HPLC.
The scope of the reaction was examined under optimized
reaction conditions, and the results are compiled in
Synlett 2011, No. 7, 943–946 © Thieme Stuttgart · New York

LETTER
Ring-Opening Reactions of Oxabicyclic Alkenes with Alkenyl Boronic Acids
945
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The absolute configuration of product 3c was assigned as
1R,2R by comparison its optical rotation with that report-
ed in literature.15
In summary, we have developed an efficient palladacycle-
catalyzed asymmetric ring-opening reaction of oxabicycle
alkenes with alkenyl boronic acids to afford the corre-
sponding products in good to excellent yields and enanti-
oselectivities. Further investigations on the applications
of this method in organic synthesis as well as on the un-
derstanding of the reaction mechanism are in progress.
Acknowledgment
We are grateful for financial support from the Major Basic Research
Development Program (2011CB808700), National Natural Science
Foundation of China (20872161, 20821002, 21032007), Chinese
Academy of Sciences, and Science and Technology Commission of
Shanghai Municipality (10ZR1436800).
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(16) A Representative Procedure for Palladacycle 4
Catalyzed Asymmetric Ring-Opening Reactions of
Oxabicyclic Alkenes with Alkenyl Boronic Acids (Table
2, Entry 3)
To a mixture of 7-oxabicycle alkene 1a (28.8 mg, 0.2 mmol),
(E)-hex-1-enylboronic acid (2c, 38.4 mg, 0.3 mmol), and
palladacycle 4 (6.0 mg, 5 mol%) in CH2Cl2 (3 mL) was
added a solution of CsF in H2O (5 M, 0.1 mmol, 20 mL) at
0 °C with stirring. The reaction was monitored by TLC until
completion. The solvent was removed under reduced
pressure. The residue was purified by column chromatog-
raphy (PE–CH2Cl2 = 2:1, v/v) to afford 42 mg of oil product
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Asymmetry 2007, 18, 251. (b) Zhang, T.-K.; Mo, D.-L.; Dai,
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Synlett 2011, No. 7, 943–946 © Thieme Stuttgart · New York

946
X.-J. Huang et al.
LETTER
3c, 92% yield, ee: 75%. [a]D25 –193 (c 1.06, CHCl3). HPLC:
Chiralcel OD (250 mm × 4.6 mm), n-hexane–i-
PrOH = 98:2, 1.0 mL/min, 254 nm, tR = 8.7 min, 10.6 min.
1H NMR (400 MHz, CDCl3): d = 0.87 (t, J = 6.8 Hz, 3 H),
1.26–1.37 (m, 4 H), 1.85 (d, J = 8.0 Hz, 1 H), 2.02 (dd,
J = 6.8, 14.0 Hz, 2 H), 3.08–3.13 (m, 1 H), 4.79 (t, J = 6.8
Hz, 1 H), 5.33 (dd, J = 8.8, 15.2 Hz, 1 H), 5.69–5.76 (m, 1
H), 5.93 (dd, J = 4.8, 9.6 Hz, 1 H), 6.48 (d, J = 9.6 Hz, 1 H),
7.06 (t, J = 3.6 Hz, 1 H), 7.22–7.25 (m, 2 H), 7.43 (t, J = 4.0
Hz, 1 H). MS (EI): m/z (rel.) = 228 (45) [M+], 167 (67), 165
(30), 146 (100), 131 (53), 128 (42), 118 (69), 115 (46).
Synlett 2011, No. 7, 943–946 © Thieme Stuttgart · New York

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