Palladium-catalyzed asymmetric coupling cyclization of terminal γ-allenols with aryl iodides

Article abstract of DOI:10.1039/c3cc40892b

A Pd-catalyzed asymmetric coupling cyclization of γ-allenols has been developed. Styrenyl derivatives can be prepared in 60-86% yields with ee values ranging from 85-92%.

Full text of DOI:10.1039/c3cc40892b

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Palladium-catalyzed asymmetric coupling cyclization of
terminal c-allenols with aryl iodides†
Xi Xiea and Shengming Ma*ab
Cite this: Chem. Commun., 2013,
49, 5693
Received 2nd February 2013,
Accepted 14th April 2013
DOI: 10.1039/c3cc40892b
www.rsc.org/chemcomm
A Pd-catalyzed asymmetric coupling cyclization of c-allenols has 94–98% ee7a and the 3-substitued pyrazolidines with 92–95% ee,7b
been developed. Styrenyl derivatives can be prepared in 60–86% respectively. Thus, we have a strong interest in the application of
yields with ee values ranging from 85–92%.
readily commercially available bidentate phosphine ligands to the
cyclization of functionalized allenes. In this communication, we
Transition metal-catalyzed asymmetric allylic substitution of allylic report the palladium-catalyzed asymmetric coupling cyclization of
acetates or carbonates is a powerful and versatile method for the g-allenols with aryl iodides using bisphosphine ligand (R,R)-L1
construction of optically active chiral organic molecules in a non- developed by Trost et al. with the observation of a very unique effect
racemic form. This reaction has been well-established and the of mixed solvents.
nucleophile scope has been expanded to allow for the use of carbon,
We started our investigation on the reaction of 4,5-hexadien-1-ol
nitrogen, oxygen, sulfur, and phosphorus nucleophiles to construct 1a with iodobenzene and K3PO4 as the base in CH3CN catalyzed by
C–C, C–N, C–O, C–S, and C–P bonds.1 It is known that the Pd(dba)2 and a chiral ligand. The chiral diphenylphosphinobenzoic
carbometallation of allenes would result in the formation of
2-substituted allylic metallic intermediates,2 which could, in principle, Table 1 The effect of catalyst and ligand on the Pd(0)-catalyzed enantio-
selective cyclization of 1a with iodobenzenea
also undergo the asymmetric allylic substitution reaction. However,
successful reports on this reaction with a 2-substitued p-allylic
palladium intermediate are very limited.3 Hiroi et al. reported
that the carbopalladation of 1-phenyl-1,2-butadiene with sodium
malonate using (R)-(S)-bppfOAc4a afforded allylic malonate with 96%
ee although we have not been able to reproduce this result; the
carbopalladation of 2-(N-allenyl)-aminophenyl iodides and subse-
quent intramolecular amination using (S)-Tol-BINAP afforded cyclic
indole derivatives up to 88% ee.4b Larock and Zenner developed
the palladium-(R,R)-Bn-Box-catalyzed asymmetric hetero- and carbo-
annulation of allenes using functionally substituted aryl or vinyl
iodides in 21–95% yields and 46–88% ee.5 Our group has also used
the same chiral ligand to synthesize other heterocycles such as
butenolides6a and pyrazolidines6b with 80–84% ee. In 2009, this
Entry L (X mol%)
t (h) Yieldb (ee) of 2a (%) Recovery of 1a b (%)
group reported the development of two new ligands, i.e., a- or
b-naphthylmethyl spiro-Box, which has been demonstrated for the
enantioselective Pd-catalyzed cyclization of 2-iodoanilines with
allenes and the enantioselective cyclization of 3,4-allenyl hydrazines
with organic halides affording 2H-indolines in good yields with
1c,d
2
(R,R)-L1 (5.5) 72
(R,R)-L2 (7.5) 48
(R,R)-L3 (7.5) 24
38 (80)
71 (20)
0
41 (2)
80 (88)
87 (88)
84 (79)
81 (80)
44
0
71
42
5
3
4c,d,e (R,R)-L4 (5.5) 67
5d
6
(R,R)-L1 (6.5) 51
(R,R)-L1 (7.5) 45
(R,R)-L1 (7.5) 31
(R,R)-L1 (7.5) 31
0
0
4
7f
8g
a Shanghai Key Laboratory of Green Chemistry and Chemical Process, Department of
Chemistry, East China Normal University, 3663 North Zhongshan Road,
Shanghai 200062, P. R. China. E-mail: masm@sioc.ac.cn; Fax: +86-21-6260-9305
b State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic
Chemistry, Chinese Academy of Sciences, 345 Lingling Lu, Shanghai 200032,
P. R. China
a
The reaction was carried out with 1a (0.2 mmol), iodobenzene (1.5 mmol),
Pd(dba)2 (5 mol%), (R,R)-L1 (X mol%) and base (1.5 equiv.) in 2 mL of
CH3CN at 90 1C. b Determined by NMR analysis. c The reaction occurred at
80 1C. d 1.2 mmol of iodobenzene was used. e 3 mL of CH3CN was used.
f 2.5 mol% Pd2(dba)3ꢀCHCl3 was used. g 2.5 mol% [(C3H5)PdCl]2 was used.
† Electronic supplementary information (ESI) available. See DOI: 10.1039/c3cc40892b
c
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Table 3 Effect of mixed solvent and molecular sieves on the Pd(dba)2-(R,R)-L1
catalyzed asymmetric coupling cyclization of 1a with iodobenzenea
acid-based ligand (R,R)-L1 (Table 1, entry 1) provided the
desired product 2a in 80% ee. Use of other commonly employed
Trost ligands (Table 1, entries 2–4) offered no improvements in
terms of stereocontrol and yield. Gratifyingly, the ee value
reached 88% when the amount of ligand (R,R)-L1 was increased
to 6.5 mol% (Table 1, entry 5). Because of the observation of not-
easily-reproducible enantioselectivity under these conditions,
the amount of ligand was further increased to 7.5 mol%
(Table 1, entry 6). Examination of the palladium source showed
that both Pd2(dba)3ꢀCHCl3 and [(C3H5)PdCl]2 had no positive
influence on the ee value (Table 1, entries 7 and 8).
With Pd(dba)2 and (R,R)-L1 being identified as the optimized
catalyst system, a systematic examination of bases and solvents was
conducted (Table 2). Bases, suchas Na3PO4,K2CO3,Et3NandKOAc,all
failed to improve the enantioselectivity and yield (Table 2, entries 1–4).
Only K2CO3 gave a decent ee value with a lower conversion
(Table 2, entry 2). Several solvents were also tested. Reactions in
polar solvents such as dioxane and DMF gave moderate enantios-
electivities (Table 2, entries 5 and 7). In a less polar solvent such as
toluene, enantioselectivity was almost the same (Table 2, entry 6).
CH3CN resulted in the full conversion and best enantioselectivity.
CH3CN/solvent
(volume ratio)
Yieldb (ee)
of 2a (%)
Recovery of
Entry
MS
t (h)
1a b (%)
1
2
3
4
5
6
7
8
9
Dioxane(1 : 1)
Toluene(1 : 1)
n-BuCN(1 : 1)
Me3CCN(1 : 1)
/
/
/
/
24
26
26
25
22
24
21
24
22
72 (87)
55 (88)
24 (88)
72 (89)
81 (90)
76 (91)
47 (91)
78 (84)
79 (92)
12
21
34
5
0
0
31
0
3
Me3CCN(1 : 1)
4 Å
4 Å
4 Å
4 Å
3 Å
Me3CCN(1.2 : 0.8)
Me3CCN(1.5 : 0.5)
Me3CCN(0.8 : 1.2)
Me3CCN(1.2 : 0.8)
a
The reaction was carried out with 1a (0.2 mmol), iodobenzene
(0.3 mmol), Pd(dba)2 (5 mol%), (R,R)-L1 (7.5 mol%), base (1.5 equiv.),
b
MS (80 mg) in 2 mL of solvent at 90 1C. Determined by NMR analysis.
With the optimized reaction conditions in hand, a range of aryl
iodides were investigated. The results are listed in Table 4. Aryl iodides
bearing electron-withdrawing (Table 4, entries 4–9) and electron-
donating groups (Table 4, entries 1–3) proceeded smoothly to afford
the corresponding 2-alkenyltetrahydrofurans in moderate to good
yields and enantioselectivities at 90 1C within 24–67.7 h. The substitu-
tion pattern and electronic property of the phenyl ring has an obvious
effect on the enantioselectivity, the reaction time and the concen-
tration needed for the reaction to reach completion: those bearing
electron-donating groups usually required less reaction time and
lower concentration as compared to the electron-withdrawing ones.
Table 2 Base and solvent effects on the Pd(dba)2-(R,R)-L1-catalyzed asymmetric
coupling cyclization of 1a with iodobenzenea
Yieldb (ee)
of 2a (%)
Recovery of
Entry
Solvent
Base
t (h)
1a b (%)
1
2
3
4
5
6
7
CH3CN
CH3CN
CH3CN
CH3CN
Dioxane
Toluene
DMF
Na3PO4
K2CO3
KOAc
27
33
10
35
39
42
37
7 (76)
12 (87)
85 (35)
10 (25)
53 (80)
74 (77)
18 (67)
66
67
0
49
28
8
Table 4 Coupling cyclization of 1a with different aryl halidesa
Et3N
K3PO4
K3PO4
K3PO4
18
a
The reaction was carried out with 1a (0.2 mmol), iodobenzene
(0.3 mmol), Pd(dba)2 (5 mol%), (R,R)-L1 (7.5 mol%) and base (1.5 equiv.)
b
in 2 mL of solvent at 90 1C. Determined by NMR analysis.
Entry R
t (h) Conc. (mol Lꢁ1) Yield of 2b (%) ee of 2 (%)
We then examined some binary solvent systems and addi-
tives in this reaction. When CH3CN was mixed with other
solvents (1/1 by volume), for instance, dioxane, toluene,
CH3(CH2)3CN, the ee value remained the same as that obtained
with CH3CN (Table 3, entries 1–3). But when (CH3)3CCN was
used, the ee value was increased to 89% (Table 3, entry 4). By
considering the effect of water on this reaction, fortunately, the
addition of 4 Å molecular sieves into the mixed solvent CH3CN–
(CH3)3CCN further improved the ee value to 90% (Table 3, entry 5).
After screening the volume ratio of these two solvents, it
showed that the best ee value was realized when the ratio of
CH3CN/(CH3)3CCN was 1.5 : 1 (Table 3, entry 6) with full con-
version of the starting material. After replacing the 4 Å mole-
cular sieves with 3 Å molecular sieves, the ee value was
1
2
3
4
C6H5
4-MeOC6H4
3,5-Me2C6H3 32 0.125
4-Et2NCOC6H4 40 0.167
3-Et2NCOC6H4 67.7 0.167
4-IC6H4
4-BrC6H4
26 0.100
24 0.125
78
82
76
75
86
60
78
72
67
(R)-92 (2a)
(R)-88 (2b)
(R)-89 (2c)
(R)-90 (2d)
(R)-91 (2e)
(R)-88 (2f)
(R)-85 (2g)
(R)-87 (2h)
(R)-89 (2i)
5
6c
7
45 0.250
43 0.250
8
4-CH3COC6H4 47 0.167
4-EtOCOC6H4 39 0.167
9d
a
The reaction was carried out with 1a (1.0 mmol), aryl iodide
(1.5 mmol), Pd(dba)2 (5 mol%), (R,R)-L1 (7.5 mol%), 3 Å molecular
sieves (400 mg) and K3PO4 (1.5 equiv.) in CH3CN–(CH3)3CCN (1.5/1 by
b
c
volume). Isolated yield. 1.2 equiv. of 1,4-diiodobenzene were used.
d
The reaction was carried out on a 0.5 mmol scale.
We next examined the scope of the g-allenols with the reaction of
improved slightly to 92% (Table 3, entry 9). Overall, the best iodobenzene. Methyl groups were well tolerated at several positions,
results were obtained by using 1.5 equiv. of K3PO4 as the base in including the a, b and g positions of the allenols (Table 5, entries 1–3).
CH3CN–(CH3)3CCN in the presence of 3 Å molecular sieves The closer the methyl substituents to the allene moieties, longer
under the catalysis of 5 mol% Pd(dba)2 and 7.5 mol% (R,R)-L1. reaction time and higher concentration were required.
c
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Table 5 Reaction of phenyl iodide with different allenolsa
Conc.
Yield of
ee of
2 (%)
Entry R1
R2
R3
Time (h) (mol Lꢁ1
)
2b (%)
1
2
3
CH3
H
H
H
CH3
H
H
H
50
22
0.250
0.167
0.149
78((R)-2j)
81((R)-2k) 85
79((R)-2l) 86
88
CH3 27.5
a
The reaction was carried out with g-allenol (0.5 mmol), iodobenzene
(0.75 mmol), Pd(dba)2 (5 mol%), (R,R)-L1 (7.5 mol%), 3 Å molecular
sieves (200 mg) and K3PO4 (1.5 equiv.) in CH3CN–(CH3)3CCN (1.5/1 by
b
volume). Isolated yield.
The one gram-scale of this reaction has also been demonstrated
(Scheme 1), affording the desired product in 85% yield with 90% ee.
Scheme 3 Proposed mechanism and prediction of the absolute configuration
of the product.
Scheme 1 One gram-scale synthesis of (R)-2-(1-(40-bromobiphenyl-4-yl)-
vinyl)tetrahydrofuran.
Financial support from the National Natural Science Foun-
dation of China (21232006) and the National Basic Research
The absolute configuration of 2a was determined to be R by Program of China (2009CB825300) is greatly appreciated. We
comparison of the tR and specific rotation of the authentic thank Qiankun Li in this group for reproducing the results of
(S)-2a (Scheme 2), which was prepared in situ by the Wittig the preparation of 2d, 2i, 2k.
methenylation of (S)-phenyl(tetrahydrofuran-2-yl)methanone8
derived from the reaction between (S)-tetrahydrofuran-2-
Notes and references
carboxylic acid and phenylmagnesium bromide.9
1 For reviews, see: (a) B. M. Trost, Acc. Chem. Res., 1996, 29, 355;
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(c) Z. Lu and S. Ma, Angew. Chem., Int. Ed., 2008, 47, 258;
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Substitution in Organic Synthesis, Springer-Verlag, 2012.
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of Organopalladium Chemistry for Organic Synthesis, Wiley-Inter-
science, New York, 2002, p. 1491; (e) S. Ma, Acc. Chem. Res., 2003,
36, 701; ( f ) N. Krause and A. S. K. Hashmi, Modern Allene Chemistry,
Wiley-VCH, Weinheim, Germany, 2004, vol. 1–2; (g) S. Ma, Chem. Rev.,
2005, 105, 2829; (h) T. Ryoichi, S. Misa, S. Fumie and U. Hirokazu,
Tetrahedron Lett., 2005, 46, 329; (i) S. Ma, Pure Appl. Chem., 2006, 78, 197;
( j) T. Bai, S. Ma and G. Jia, Coord. Chem. Rev., 2009, 253, 423;
(k) M. Jeganmohan and C. Cheng, Chem. Commun., 2008, 3101.
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Scheme 2 Preparation of (S)-2-(1-phenylvinyl)tetrahydrofuran.
A mechanistic proposal for the prediction of the absolute
configuration10 in the products with the Trost ligand is shown in
Scheme 3. The regioselective carbopalladation of PhPdI, which is
formed in situ from the oxidative addition of Pd(0) with iodo-
benzene, with g-allenols at the center carbon atom forms the
p-allylic palladium complex syn-C, not syn-B due to the unfavorable
steric interactions between the (CH2)3OH and the coordinated
palladium as well as the chiral ligand. Subsequent nucleophilic
attack of the hydroxyl group leads to the product with the
observed absolute configuration along with regeneration of
Pd(0) catalyst A.
4 (a) K. Hiroi, F. Kato and A. Yamagata, Chem. Lett., 1998, 397;
(b) K. Hiroi, Y. Hiratsuka, K. Watanabe, I. Abe, F. Kato and
M. Hiroi, Tetrahedron: Asymmetry, 2002, 13, 1351.
In summary, we have successfully developed a facile access to
enantioenriched tetrahydrofurans via Pd(0)-catalyzed asymmetric
coupling cyclization of terminal g-allenols with aryl iodides in
60–86% yields with 85–92% ee with the observation of a unique
solvent effect. Further investigations in this area, especially the
scope of different organic halides and nucleophiles, as well as the
development of new chiral ligands for such reactions are ongoing
in our laboratory.
5 (a) R. C. Larock and J. M. Zenner, J. Org. Chem., 1995, 60, 482;
(b) J. M. Zenner and R. C. Larock, J. Org. Chem., 1999, 64, 7312.
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10 B. M. Trost, M. R. Machacek and A. Aponick, Acc. Chem. Res., 2006,
39, 747.
c
This journal is The Royal Society of Chemistry 2013
Chem. Commun., 2013, 49, 5693--5695 5695