Pd-Catalyzed stereospecific allyl-aryl coupling of allylic alcohols with arylboronic acids

Article abstract of DOI:10.1039/c3cc45053h

An efficient method for Pd-catalyzed stereospecific allyl-aryl coupling of allylic alcohols with arylboronic acids has been described. The reactions proceeded smoothly in the presence of Pd₂(dba)₃· CHCl₃ and racemic BINAP

Full text of DOI:10.1039/c3cc45053h

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Communication
Pd-Catalyzed stereospecific allyl aryl coupling of allylic alcohols with
arylboronic acids
Jiang Ye, Jingming Zhao, Jing Xu, Yuxue Mao and Yong Jian Zhang*
Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX
5
DOI: 10.1039/b000000x
recent success in Pdꢀcatalyzed stereospecific crossꢀcoupling
50 of allylic carbonates with arylboronic acids,10 herein we
disclose corresponding stereospecific coupling reaction
directly using allylic alcohols, a greener and practical protocol
that allows rapid access to allyl aryl coupling products with
high stereospecificities.
An efficient method for Pd-catalyzed stereospecific allyl aryl
coupling of allylic alcohols with arylboronic acid has been
described. The reactions proceeded smoothly in the presence
of Pd2(dba)3•CHCl3 and racemic BINAP under mild and
10 neutral conditions, affording allyl aryl coupling products in
moderate to high yields with excellent stereospecificities.
55 Initially, we conducted the reaction of enantioenriched allylic
alcohol 1a (96% ee) as
a
standard substrate with
Transition metalꢀcatalyzed crossꢀcoupling reactions of allylic
electrophiles with aryl nucleophiles are powerful tools for the
construction of valuable allyl aryl coupling compounds by
15 the formation of a new C C bond.1,2 The allyl aryl coupling
reaction with arylboronic acid derivatives has emerged as
being advantageous in light of their availability, stability, and
phenylboronic acid (2a) under our previous conditions10 for
the coupling reaction of allylic carbonates (Table 1, entries 1
and 2). However, the reaction conditions were not effective
60 for the direct coupling of allylic alcohol 1a. Remarkably, by
Table 1 Optimization studies for Pdꢀcatalyzed stereospecific allyl aryl
coupling of (S)ꢀ1a with 2aa
ease of handling.3 Although some transition metal such as Rhꢀ
4
,
Pd(II)ꢀ5 and Cu6ꢀcatalyzed stereoselective allylic arylation
20 reactions using arylboronic acids or their derivatives have
been reported, Pdꢀcatalyzed Suzuki Miyaura coupling of
allylic electrophiles have mostly been confined to afford
linear allyl aryl coupling products.7 In contrast, the coupling
reaction of 1,3ꢀdisubstituted secondary and potentially
25 enantioenriched allylic partners have been much less explored
despite the reaction provides the coupling products with a
stereogenic center. Until recently, Uozimi,8 Tian9 and our
group10 accomplished respectively Pdꢀcatalyzed stereospecific
allyl aryl coupling reactions of enantioenriched allylic
30 electrophiles with arylboronic acids, offering allyl aryl
coupling products with high stereospecificity.
Direct crossꢀcoupling between readily available allylic
alcohols and arylboronic acids is undoubtedly an atomꢀ
economical and greener process due to avoid further
35 activation of allylic alcohols to their esters, carbonates or
phosphonates et al.11 In this context, although hydroxyl group
is a reluctant leaving group, some approaches for transition
metalꢀcatalyzed crossꢀcoupling of allylic alcohols with
arylboronic acids have been established.12 However, the
40 reactions have mostly been limited for primary allylic
alcohols. Tsukamoto and coꢀworkers investigated that Pdꢀ
catalyzed allyl aryl coupling reaction of chiral secondary
allylic alcohol with phenylboronic acid, but the reaction
afforded a racemic product.12a In spite of chiral allylic
45 alcohols are readily accessible by the numerous asymmetric
synthetic methods, to our knowledge, the corresponding
stereospecific crossꢀcoupling of enantioenriched allylic
alcohols with arylboronic acids are unknown. Based on our
entry
1
2
3
4
Pd
ligand
ꢀ
racꢀBINAP
racꢀBINAP
solvent conv. (%)b ee (%)c
Pd(OAc)2
Pd(OAc)2
[Pd(allyl)Cl]2
Pd2(dba)3•CHCl3 racꢀBINAP
Pd(PPh3)4
Pd2(dba)3•CHCl3 racꢀBINAP toluene
Pd2(dba)3•CHCl3 racꢀBINAP CyH
Pd2(dba)3•CHCl3 racꢀBINAP toluene
Pd2(dba)3•CHCl3 racꢀBINAP toluene
Pd2(dba)3•CHCl3
Pd2(dba)3•CHCl3
Pd2(dba)3•CHCl3
Pd2(dba)3•CHCl3
Pd2(dba)3•CHCl3
Pd2(dba)3•CHCl3
Pd2(dba)3•CHCl3
Pd2(dba)3•CHCl3 racꢀBINAP toluene
Pd2(dba)3•CHCl3 racꢀBINAP toluene
Pd2(dba)3•CHCl3 racꢀBINAP toluene
H2O
THFd
THF
THF
THF
10
21
0
ND
ND
ꢀ
95
5
96
96
96
62
8
86 (78)
68 (48)
99 (91)
65 (54)
85 (73)
99 (85)
79 (74)
46 (43)
0
27 (20)
45 (41)
68 (63)
44 (30)
68 (67)
99 (92)
99 (91)
5
6
ꢀ
7
8e
9f
10
11
12
13
14
15
16
17g
18h
19i
PPh3
PCy3
P(C6F5)3
DPPE
DPPB
DPPF
toluene
toluene
toluene
toluene
toluene
toluene
toluene
71
ꢀ
96
92
86
65
96
81
56
Xantphos
a
Conditions: Pd (2.0 mol%), ligand (2.0 mol% for bisphosphines; 4.0
65 mol% for monophosphines), 1a (0.4 mmol), 2a (0.6 mmol), solvent (0.8
mL), 50 oC, 18 h. b Determined by 1H NMR of the crude reaction mixture.
c
Isolated yields are shown in parentheses. Determined by chiral HPLC
analysis. The absolute configuration was determined by comparison the
sign of optical rotation with that of the reported data.10 d With 5 equiv. of
70 H2O. e The reaction was conducted at 40 oC. f The reaction was conducted
at 70 C. 1 mol% of catalyst loading. 4 mol% of catalyst loading.
mol% of catalyst loading. CyH: cyclohexane. ND: not determined.
o
g
h
i
8
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Table 3 PdꢀCatalyzed stereospecific allyl aryl coupling of various allylic
alcohols (S)ꢀ1 with 2aa
means of further screening of palladium source (entries 3 5),
we found that the reaction proceeded well in the presence of
Pd2(dba)3•CHCl3 (1 mol%) and racemic BINAP (2 mol%) in
entry
1
allylic alcohol
OH
product
Ph
yield (%)b ee (es) (%)c
o
THF at 50 C for 18 h, affording coupling product 3a in 78%
5
yield
with
complete
regioselectivity
and
high
76
94 (98)
Ph
Ph
nBu
Ph
nBu
enantiospecificity (95% ee) with inversed absolute
configuration, and no E/Z isomerization and βꢀhydride
elimination were observed (entry 4). However, the reaction
with Pd(PPh3)4 as a catalyst gave almost racemic product
(S)-1b
(R)-3i
(96% ee)
OH
Ph
2
3
68
86
91 (93)
91 (93)
Ph
OH
Me
Ph
Ph
Ph
Me
(S)-1c
(R)-3j
(98% ee)
10 (entry 5). Further investigation of solvent effect demonstrated
that toluene is a best solvent for the reaction, giving product
3a in 91% yield with complete enantiospecificity (96% ee,
entry 6). However, the reactions did not work at all in CH2Cl2,
ether, pentane, acetonitrile, methanol or pure water. We also
15 demonstrated that 50 oC is an ideal temperature for the
Me
Me
(S)-1d
(98% ee)
OH
(R)-3k
Ph
Me
4
5
82
93 (98)
Me
(S)-1e
(95% ee)
OH
o
(R)-3l
reaction. Lowering the reaction temperature to 40 C resulted
Ph
in lower conversion (entry 8), and higher reaction temperature
led to erosion of enantioselectivity (entry 9). The reaction
efficiency was also sensitive to the nature of the phosphine
20 ligand. When using PPh3 as a ligand, the reaction gave almost
racemic product (entry 10). The reaction with σꢀdonating
tricyclohexylphosphine resulted in low conversion and
enantioselectivity (entry 11), and the reaction did not proceed
at all in the presence of electronic deficient phosphine ligand,
25 P(C6F5)3 (entry 12). Bisphosphine ligands such as DPPE,
DPPB, DPPF and Xantphos promoted reaction with good to
excellent enantiospecificities, but the reactions led to low
conversions (entries 13 16). Notably, bisphosphine ligands
played an important role for high stereospecificities in the
30 coupling reaction.13 The reason can be explained that Pd(0)
complex with PPh3 acts as a nucleophile to isomerize πꢀ
allylpalladium intermediates via SN2ꢀtype attack leading to
loss of stereospecificity in allylic substitutions reported by
Bäckvall and Granberg.14 This isomerization due to PdꢀPd
35 displacement can be inhibited by the use of chelated bidentate
ligand.14 To prove this explanation, we examined the reaction
under different catalyst loading (entries 17 19). Clearly, the
stereospecificities were significantly decreased with
increasing catalyst loading; 56% ee was observed when the
91d
91d
96 (98)
97 (99)
Me
Ph
Me
Me
Ph
(S)-1f
(98% ee)
(R)-3m
Ph
Ph
(S)-3n
(R)-3m:(S)-3n = 42:58
50
a
b
c
The reaction conditions as described for Table 2. Isolated yield.
Determined by chiral HPLC analysis. d Total isolated yield of (R)ꢀ3m and
(S)ꢀ3n.
With the optimized conditions in hand, the reaction scope of
55 the allyl aryl coupling reaction with respect to substituted
arylboronic acids was evaluated. As shown in Table 2, the
coupling reaction of enantioenriced allylic alcohol 1a (96% ee)
with various substituted arylboronic acids with different
electronic or steric natures proceeded to the corresponding
60 allyl aryl coupling product (R)ꢀ3a 3h in moderate to high
level of isolated yields with complete regioselectivities and
excellent enantiospecificities, no E/Z isomerizations and βꢀ
hydride eliminations were observed for all of the examples.
The reactions with paraꢀsubstituted arylboronic acids
65 exhibited relatively low conversions.
Next, we further investigated the coupling reaction of various
allylic alcohols 1 with phenylboronic acid (2a) under our
optimized conditions (Table 3). The reactions of chiral allylic
alcohols 1b 1e with 2a gave corresponding coupling
70 products 3i 3l as single regioisomers in good yields with
excellent enantiospecificities (93 98% es, entries 1 4). The
coupling reaction of the sterically less differentiated 1f (98%
ee) with 2a furnished a mixture of the two regioisomers, 3m
and 3n with a ratio of 42:58 in 91% of total yield with
75 excellent chirality transfer for the two isomers (entry 5).
These results indicated that the regioselectivity of the
coupling reaction is controlled by the steric differences of the
1ꢀ and 3ꢀsubstituents of the allylic alcohols.2
40 reaction proceed in the presence of
4
mol% of
Pd2(dba)3•CHCl3 and 8 mol% of racemic BINAP (entry 19).
Table 2 PdꢀCatalyzed stereospecific allyl aryl coupling of (S)ꢀ1a with
various arylboronic acids 2a
entry
1
2
Ar
Ph (2a)
yield (%)b
ee (%)c
96
94
95
95
95
95
89
94
es (%)d
100
98
99
99
99
99
93
98
91
81
84
47
60
45
63
91
To gain more mechanistic information for the stereospecific
80 allyl aryl coupling process, we examined the reaction of
enantioenriched (S)ꢀ1a using both enantiomers of ligand. As
2ꢀMeC6H4 (2b)
3ꢀMeOC6H4 (2c)
4ꢀMeC6H4 (2d)
4ꢀtBuC6H4 (2e)
4ꢀMeOC6H4 (2f)
4ꢀClC6H4 (2g)
2ꢀnaphthyl (2h)
3
4e
5e
6e
7e
8
shown in Eq. 1, there were
a slight level of double
diastereodifferentiation but both reactions afforded the
product with inversed configuration as the predominant
85 outcome. These results indicated that the stereochemistry of
the reaction exclusively depended on the configuration of
allylic alcohol. On the other hand, performing the reactions of
a
b
45 Conditions: 1a (0.4 mmol), 2 (0.6 mmol), toluene (0.8 mL). Isolated
c
d
yield. Determined by chiral HPLC analysis. Enantiospecificity (es) =
eeproduct/eesubstrate × 100%. e The reactions were carried out for 24 h.
2
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DOI: 10.1039/C3CC45053H
DOI: 10.1039/b000000x/
40
45
50
55
60
65
70
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85
1
For reviews on the transition metalꢀcatalyzed crossꢀcoupling
reactions, see: (a) MetalꢀCatalyzed CrossꢀCoupling Reactions, 2nd
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J. Tsuji, Acc. Chem. Res., 1969, 2, 144.
2
racemic allylic alcohol 1a with both enantiomers of BINAP
afforded coupling product 3a with poor enantioselectivities.
Although an inꢀdepth investigation remained to be conducted,
the plausible reaction pathway for the crossꢀcoupling of
allylic alcohols with arylboronic acids can be proposed as
outlined in Figure 1.10,11,12a Firstly, hydroxyl group of allylic
alcohol 1a is activated by arylboronic acid, and then πꢀ
allylpalladium species is formed by the oxidative addition of
10 Pdꢀcomplex to the activated chiral (S)ꢀ1a from the back side
stereospecifically. Palladium intermediate II subsequently
takes place the transmatalation to form allylarylpalladium III,
which undergo reductive elimination at the sterically less
hindered side to furnish the inversed allyl aryl coupling
15 product (R)ꢀ3a with excellent stereospecificity.
3
4
For reviews on SuzukiꢀMiyaura coupling, see: (a) A. Suzuki, Angew.
Chem., Int. Ed., 2011, 50, 6723; (b) G. A. Molander and B. Canturk,
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5
6
7
Figure 1. Possible reaction pathway
8
9
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In conclusion, we have developed an atomꢀeconomical
method for Pdꢀcatalyzed stereospecific allyl aryl coupling
20 reaction directly using chiral secondary allylic alcohols with
arylboronic acids. The reactions proceeded smoothly in the
presence of Pd2(dba)3•CHCl3 and racemic BINAP under mild
and neutral conditions, affording allyl aryl coupling products
in moderate to high yields with excellent enantiospecificities
25 with inversed stereochemistry. Further studies on the
exploration of the scope and the mechanism of the reaction
are currently underway, and will be reported in due course.
We gratefully acknowledge Shanghai Pujiang Program
(11PJD012), National Key Basic Research Program of China
30 (2013CB934101) and Shanghai Jiao Tong University for
financial supports.
10 (a) J. Zhao, J. Ye and Y. J. Zhang, Adv. Synth. Catal., 2013, 355, 491;
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100
Notes and references
School of Chemistry and Chemical Engineering, and Shanghai Key
Laboratory of Electrical Insulation and Thermal Aging, Shanghai Jiao
35 Tong University, 800 Dongchuan Road, Shanghai 200240, P. R. China,
Fax: 86 21 5474 1297; Tel: 86 21 5474 0787; Eꢀmail: yjian@sjtu.edu.cn
†Electronic Supplementary Information (ESI) available: [details of any
supplementary information available should be included here]. See
105 13 The similar phenomenon was also observed in Pdꢀcatalyzed allylic
azidation, see: S. I. Murahashi, Y. Taniguchi, Y. Imada and Y.
Tanigawa, J. Org. Chem. 1989, 54, 3292.
14 K. L. Granberg and J.ꢀE. Bäckvall, J. Am. Chem. Soc. 1992, 114,
6858.
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