Palladium-catalyzed formal arylacylation of allenes employing acid chlorides and arylboronic acids

Article abstract of DOI:10.1039/c4cc03173c

Palladium-catalyzed formal arylacylation of allenes using acid chlorides and arylboronic acids has been achieved. The reaction afforded the corresponding α,β-unsaturated ketones regio- and stereoselectively. the Partner Organisations 2014.

Full text of DOI:10.1039/c4cc03173c

Showcasing research from the laboratory of Yasushi Tsuji,
Department of Energy and Hydrocarbon Chemistry,
Kyoto University, Japan
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Palladium-catalyzed formal arylacylation of allenes employing
acid chlorides and arylboronic acids
The palladium-catalyzed formal arylacylation of allenes using acid
chlorides and arylboronic acids has been achieved. The reaction
afforded the corresponding α,β-unsaturated ketones regio- and
stereoselectively.
See Tetsuaki Fujihara,
Yasushi Tsuji et al.,
Chem. Commun., 2014, 50, 8476.
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Palladium-catalyzed formal arylacylation of
allenes employing acid chlorides and
arylboronic acids†
Cite this: Chem. Commun., 2014,
50, 8476
Received 29th April 2014,
Accepted 20th May 2014
Kenta Tatsumi, Tetsuaki Fujihara,* Jun Terao and Yasushi Tsuji*
DOI: 10.1039/c4cc03173c
www.rsc.org/chemcomm
Palladium-catalyzed formal arylacylation of allenes using acid chlorides using acid chlorides and hydrosilanes.14 We envisioned that
and arylboronic acids has been achieved. The reaction afforded the the use of carbon nucleophiles in place of hydrosilanes would
corresponding a,b-unsaturated ketones regio- and stereoselectively.
achieve the formal carboacylation of allenes. In this paper, we
describe the palladium-catalyzed formal arylacylation of allenes
The addition of carbonyl compounds to carbon–carbon unsaturated using acid chlorides and arylboronic acids. Notably, no direct-
bonds is an efficient method to functionalize unsaturated com- ing groups were required in the present reaction and various
pounds.1 To date, the addition of aldehydes (hydroacylation),2 a,b-unsaturated ketones are obtained regio- and stereoselectively.
formamides (hydrocarbamoylation),3 formates (hydroesterification),4
First, the reaction of 3-phenylpropionyl chloride (1a), cyclo-
and acid chlorides (chloroacylation)5 to carbon–carbon unsaturated hexylallene (2a) and phenylboronic acid (3a) was carried out in
bonds has been reported. The addition of ketone, namely the presence of a catalytic amount of Pd2(dba)3 (dba = dibenzyl-
carboacylation, is also an efficient method to synthesize highly ideneacetone) and CuCl with K3PO4 and H2O in toluene/MeCN
functionalized ketones. However, the activation of acyl–carbon (9/1, v/v) at 50 1C (Table 1). Under the standard reaction
bonds of ketones has been difficult. To achieve carboacylation, conditions (entry 1), (E)-4a was obtained with high regio- and
directing groups6 or strained structures7,8 were required. There- stereoselectivity (96/4). As a side product, a small amount of
fore, formal carboacylation using a carbon nucleophile and a ketone 5, which was formed by the Suzuki–Miyaura coupling of
carbonyl electrophile as ketone equivalents is desirable as an
alternative method. The reactions of organometallic reagents
Table 1 Optimization of reaction conditionsa
with carbon–carbon unsaturated bonds followed by trapping
with acid chlorides as the electrophile have been investigated.9
However, highly reactive organometallic reagents such as organo-
magnesium or organozinc reagents or the presence of directing
groups in unsaturated compounds were indispensable to control
the reactivity and regioselectivity. There is only one precedent
to data for the acylmetalation strategy; Miura et al. reported the
Rh-catalyzed carboacylation of norbornene using acid anhydrides
and organoboron reagents.10,11
Allenes are valuable substrates in transition-metal-catalyzed
reactions.12 In particular, allenes can be easily inserted into
Pd–C bonds to form the corresponding p-allyl Pd species.12a
Cheng and co-workers reported the acylmetalation of allenes
using acid chlorides with diborane, disilane, and distannane.13
Recently, we reported the formal hydroacylation of allenes
Total yield (E)-4a: other
of 4ab (%) isomersc
Entry Changes
5c (mmol)
1
2
3
4
5
6
7
8
9
10
Standard condition
86 (80)d
0
0
96 : 4
—
—
88 : 12
—
96 : 4
88 : 12
96 : 4
—
0.034
0
0.22
0.027
0
0.014
0.005
0.040
0
Without Pd2(dba)3
e
Addition of PPh3
In toluene as a solvent 62
In MeCN as a solvent
Without CuCl
Without H2O
H2O (8.0 equiv.)
PhB(pin) f
0
31
6
66
0
PhBF3K
0
—
0.001
a
Reaction conditions: 3-phenypropionyl chloride (1a, 0.40 mmol),
cyclohexylallene (2a, 0.20 mmol, yield and equiv. are based on this
amount), PhB(OH)2 (3a, 0.30 mmol), Pd2(dba)3ꢀCHCl3 (0.010 mmol,
5.0 mol%), CuCl (0.020 mmol, 10 mol%), K3PO4 (0.40 mmol), H2O
(4.0 equiv., 0.80 mmol) in toluene/MeCN = 9/1 (v/v, 4.0 mL), at 50 1C, for
Department of Energy and Hydrocarbon Chemistry, Graduate School of Engineering,
Kyoto University, Kyoto 615-8510, Japan. E-mail: tfuji@scl.kyoto-u.ac.jp,
ytsuji@scl.kyoto-u.ac.jp; Fax: +81-75-383-2514; Tel: +81-75-383-2515
† Electronic supplementary information (ESI) available. See DOI: 10.1039/
c4cc03173c
b
c
3 h. Yield by the GC internal standard method. Determined by GC.
d
e
f
Isolated yield of pure (E)-4a. P/Pd = 2. pin = pinacolato.
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1a with 3a,15 was detected. Notably, styrene formation via the
Various acid chlorides reacted with 2a and 3a (Table 2). The
decarbonylation of 1a followed by b-hydrogen elimination was reactions of aliphatic acid chlorides (1b–g) gave the corre-
not observed. With a column chromatography, pure (E)-4a was sponding products (4b–4g) in good to high yields (entries 1–6).
isolated in 80% yield. Without Pd2(dba)3, the reaction did not Ether (entry 3) and ester (entry 4) functional groups were
proceed at all (entry 2). In this reaction, the addition of auxiliary tolerated in the reaction. In the case of cyclohexanecarbonyl
ligands such as PPh3 inhibited the formation of 4a and only 5 chloride (1f), the desired product was obtained in a moderate
was obtained in 73% yield (0.22 mmol) based on 3a (entry 3). yield in the presence of 8.0 equiv. of H2O (entry 5). In general,
When MeCN was removed from the reaction system (only less reactive acid chlorides 1 tend to require comparatively
toluene was used as the solvent), both the yield and selectivity more amounts of H2O to ensure good yields. The reaction with
decreased considerably (entry 4). In contrast, the use of MeCN pivaroyl chloride afforded the E/Z mixture of the products in
as the solvent did not afford 4a at all (entry 5). In the Suzuki– moderate yield with a ratio of E/Z = 87/13 (entry 6). Benzoyl
Miyaura coupling, it was known that the addition of a Cu salt chloride derivatives (1h–j) with electron-donating (1i) and
promotes the coupling reaction.15d,16 Thus, without CuCl, the electron-withdrawing substituents (1j) afforded the corre-
yield of 4a decreased to 31% (entry 6). The addition of H2O was sponding products in good yields (entries 7–9).
also found to be important in this reaction; the yield of 4a was
Next, various allenes were reacted with 1a and 3a in the
very low in the absence of H2O (entry 7). In contrast, when the presence of suitable amounts of H2O (Table 3). Although the
amount of H2O was increased to 8.0 equiv. (1.6 mmol), the yield reaction of 2b with a primary alkyl group gave the product (4k)
of 4a decreased and that of 5 increased (entry 8; cf. entry 1). The in moderate yield (entry 1), those of 2c and 2d bearing a
use of PhB(pin) or PhBF3K instead of PhB(OH)2 did not afford secondary and a tertiary alkyl group afforded the corresponding
4a at all (entries 9 and 10).
products (4l and 4m) in high yields (entries 2 and 3). The
reaction of phenylallene (2e) gave 4n in a low yield (entry 4).
1,1-Disubstituted (2f) and 1,3-disubstituted (2g) allenes success-
fully gave the corresponding products (4o and 4p) in high yields
(entries 5 and 6).
Table 2 Scope of acid chloridesa
Entry Acid chloride 1 Product (E)-4
H2O (equiv.) Yieldb (%)
Various arylboronic acids (3) afforded the corresponding
a,b-unsaturated ketones (4) in high yields (Table 4). In the case
1
2
3
4
5
6
6.0
4.0
4.0
4.0
8.0
6.0
80
80
84
69
60
57c
Table 3 Scope of allenesa
Entry Allene 2
Product (E)-4
H2O (equiv.) Yieldb (%)
1c
3.5
6.0
8.0
60
79
90
2
3
4
5
5.0
38
5.0
5.0
81
91
6
7
8
9
1h: R = H
1i: R = MeO
1j: R = Cl
4h
4i
4j
6.0
8.0
6.0
73
66
72
a
a
Reaction conditions: 1a (0.40 mmol), allene (2, 0.20 mmol, yield and
equiv. are based on this amount), 3a (0.30 mmol), Pd2(dba)3ꢀCHCl3
(0.010 mmol, 5.0 mol%), CuCl (0.020 mmol, 10 mol%), K3PO4
(0.40 mmol), H2O (x equiv.) in toluene/MeCN = 9/1 (v/v, 4.0 mL), at
Reaction conditions: acid chloride (1, 0.40 mmol), 2a, (0.20 mmol, yield
and equiv. are based on this amount), 3a (0.30 mmol), Pd2(dba)3ꢀCHCl3
(0.010 mmol, 5.0 mol%), CuCl (0.020 mmol, 10 mol%), K3PO4 (0.40 mmol),
H2O (x equiv.) in toluene/MeCN = 9/1 (v/v, 4.0 mL), at 50 1C, for 3 h.
b
c
b
c
50 1C, for 3 h. Isolated yield of (E)-4k-p. 3a (0.40 mmol).
Isolated yield of (E)-4b–j. Mixture of isomers (E/Z = 87/13).
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Table 4 Scope of boronic acidsa
affords an acylpalladium species B (step a). Next, the fast
insertion of an allene (2) into B instead of the transmetalation
with 3 (step b0) or decarbonylation (step b00) gives a p-allylpalladium
intermediate C (step b). The transmetalation of aryl boronic acid (3)
with C in the presence of a base and CuCl affords an arylpalladium
species D (step c). Finally, the reductive elimination of D provides
the a,b-unsaturated ketone (4) and regenerates the palladium(0)
species A (step d). Water must play an important role in activating
boronic acid and/or Pd catalyst species.15c,17 In the present
formal arylacylation, the adducts can be efficiently and selec-
tively obtained by simply adjusting the amount of H2O depend-
ing on reactivity of substrates.
Entry Boronic acid 3 Product (E)-4
H2O (equiv.) Yieldb (%)
1
2
3
4
5
6
3b: R = MeO
3c: R = F
3d: R = Cl
3e: R = Br
3f: R = CN
4q
4r
4s
4t
2.0
7.0
5.0
7.0
7.0
9.0
82
87
90
84
73
79
4u
3g: R = COOMe 4v
Notes and references
1 For a review, see: T. Fujihara, T. Iwai, J. Terao and Y. Tsuji, Synlett,
2010, 2537.
2 For reviews, see: (a) M. C. Willis, Chem. Rev., 2010, 110, 725; (b) J. C.
Leung and M. J. Krische, Chem. Sci., 2012, 3, 2202; (c) Y. J. Park,
J.-W. Park and C.-H. Jun, Acc. Chem. Res., 2008, 41, 222; (d) G. C. Fu,
in Modern Rhodium-Catalyzed Organic Reactions, ed. A. Evans, Wiley-VCH,
Weinheim, 2005, p. 79.
7
7.0
6.0
89
62
8c
3 Recent examples of hydrocarbamoylation, see: (a) T. Fujihara,
Y. Katafuchi, T. Iwai, J. Terao and Y. Tsuji, J. Am. Chem. Soc.,
2010, 132, 2094; (b) B. Li, Y. Park and S. Chang, J. Am. Chem. Soc.,
2014, 136, 1125; (c) P. A. Donets and N. Cramer, J. Am. Chem. Soc.,
2013, 135, 11772; (d) N. Armanino and E. M. Carreira, J. Am. Chem.
Soc., 2013, 135, 6814; (e) Y. Nakao, H. Idei, K. S. Kanyiva and
T. Hiyama, J. Am. Chem. Soc., 2009, 131, 5070.
a
Reaction conditions: 1a (0.40 mmol), 2a (0.20 mmol, yield and equiv. are
based on this amount), boronic acid (3, 0.30 mmol), Pd2(dba)3ꢀCHCl3
(0.010 mmol, 5.0 mol%), CuCl (0.020 mmol, 10 mol%), K3PO4 (0.40 mmol),
H2O (x equiv.) in toluene/MeCN = 9/1 (v/v, 4.0 mL), at 50 1C, for 3 h.
b Isolated yield of (E)-4q–x. c Two equiv. of 3i was used without CuCl.
4 Recent examples of hydroesterification, see: (a) Y. Katafuchi,
T. Fujihara, T. Iwai, J. Terao and Y. Tsuji, Adv. Synth. Catal., 2011,
353, 475; (b) B. Li, S. Lee, K. Shin and S. Chang, Org. Lett., 2014,
16, 2010; (c) I. Fleischer, R. Jennerjahn, D. Cozzula, R. Jackstell,
R. Franke and M. Beller, ChemSusChem, 2013, 6, 417; (d) H. Konishi,
T. Ueda, T. Muto and K. Manabe, Org. Lett., 2012, 14, 4722.
5 Recent examples of chloroacylation, see: (a) T. Iwai, T. Fujihara,
J. Terao and Y. Tsuji, J. Am. Chem. Soc., 2012, 134, 1268; (b) T. Iwai,
T. Fujihara, J. Terao and Y. Tsuji, J. Am. Chem. Soc., 2010, 132, 9602;
(c) R. Cano, M. Yus and D. J. Ramon, Tetrahedron, 2013, 69, 7056.
6 (a) A. M. Dreis and C. J. Douglas, J. Am. Chem. Soc., 2008, 131, 412;
(b) M. T. Wentzel, V. J. Reddy, T. K. Hyster and C. J. Douglas, Angew.
Chem., Int. Ed., 2009, 48, 6121.
7 For reviews, see: (a) T. Seiser, T. Saget, D. N. Tran and N. Cramer,
Angew. Chem., Int. Ed., 2011, 50, 7740; (b) M. Murakami, M. Makino,
S. Ashida and T. Matsuda, Bull. Chem. Soc. Jpn., 2006, 79, 1315;
(c) D. Bellus and B. Ernst, Angew. Chem., Int. Ed. Engl., 1988, 27, 797.
8 For recent examples, see: (a) L. Souillart, E. Parker and N. Cramer,
Angew. Chem., Int. Ed., 2014, 53, 3001; (b) T. Xu and G. Dong, Angew.
Chem., Int. Ed., 2012, 51, 7567; (c) T. Xu, H. M. Ko, N. A. Savage and
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of a reactive arylboronic acid bearing the electron-donating
substituent (3b), the corresponding product was obtained in
82% yield in the presence of a smaller amount (2.0 equiv.) of H2O
(entry 1). On the other hand, more H2O (5–9 equiv.) was beneficial to
realize high yields with less reactive 3c–g bearing electron-
withdrawing substituents (entries 2–6). Under the reaction condi-
tions, chloro (3d), bromo (3e), cyano (3f), and methoxycarbonyl (3g)
functionalities on the phenyl rings remained intact (entries 3–6).
The reaction of 1-naphtylboronic acid (3h) also afforded the
product in 89% yield (entry 7). More reactive (E)-styrylboronic
acid (3i) gave the corresponding product (4x) in a moderate yield,
even without the addition of CuCl to the catalyst system.
A plausible catalytic cycle is shown in Scheme 1. First, the
oxidative addition of an acid chloride (1) to Pd(0) species A
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alkyne, see: K. Kokubo, K. Matsumasa, M. Miura and M. Nomura,
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13 (a) F.-Y. Yang, M.-Y. Wu and C.-H. Cheng, J. Am. Chem. Soc., 2000,
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Scheme 1 Plausible mechanism.
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14 T. Fujihara, K. Tatsumi, J. Terao and Y. Tsuji, Org. Lett., 2013, 16 Examples of Pd catalyzed Suzuki coupling with Cu salts, see
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