A novel catalytic decarbonylative Heck-type reaction and conjugate addition of aldehydes to unsaturated carbonyl compounds

Article abstract of DOI:10.1016/j.tetlet.2010.08.040

A novel rhodium-catalyzed decarbonylative reaction of aldehydes with unsaturated carbonyl compounds was discovered to generate Heck-type reaction product and conjugate addition product.

Full text of DOI:10.1016/j.tetlet.2010.08.040

Tetrahedron Letters 51 (2010) 5486–5489
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
A novel catalytic decarbonylative Heck-type reaction and conjugate addition
of aldehydes to unsaturated carbonyl compounds
⇑
Luo Yang, Camille A. Correia, Xiangyu Guo, Chao-Jun Li
Department of Chemistry, McGill University, 801 Sherbrooke Street West, Montreal, Quebec, Canada H3A 2K6
a r t i c l e i n f o
a b s t r a c t
Article history:
A novel rhodium-catalyzed decarbonylative reaction of aldehydes with unsaturated carbonyl compounds
was discovered to generate Heck-type reaction product and conjugate addition product.
Ó 2010 Elsevier Ltd. All rights reserved.
Received 13 June 2010
Revised 4 August 2010
Accepted 12 August 2010
Available online 17 August 2010
Keywords:
Decarbonylative coupling
Decarbonylative addition
Rhodium-catalyzed
Aldehyde
The transition metal-catalyzed Heck-type reactions1 and conju-
gate addition reactions2 are among the most important reactions in
modern synthetic organic chemistry. Numerous biological com-
pounds, natural products, and fine chemicals have been synthe-
sized by these reactions.3 However, an archetypical requirement
of such reactions is the pre-generation of organic halides or orga-
nometallic reagents. Recently, through the work of Gooben,4
Myers,5 Tunge6 and others including us,7 decarboxylation reactions
which utilize pre-existing carboxylic acid as readily available and
convenient functional group amenable for various C–C bond for-
mation reactions have been developed. On the other hand, the
alternative decarbonylation of aldehydes, which has been fre-
quently used for the removal of aldehdye,8 has never been used
for C–C bond formation purposes until our recently reported
decarbonylative addition of aldehyde to alkyne,9 providing a novel
olefin synthesis. The success of this reaction encouraged us to ex-
plore the potential application of decarbonylation for the Heck and
conjugate additions. Herein, we will report the preliminary success
of such reactions catalyzed by rhodium (Scheme 1).
During the past decade, rhodium-catalyzed conjugate additions
of organoboron, tin, silicon, bismuth, lead, titanium, zinc, and zir-
conium reagents have been shown to be highly effective by us10
and others11 even under aqueous conditions. Furthermore, through
the work of Hayashi and many others12 various highly efficient
asymmetric conjugate addition of organoboronic acids has also
been developed. To begin our study, we examined the reaction be-
tween 4-methoxybenzaldehyde and butyl methacrylate by using
(CO)2RhI(acac), which has been shown to be a robust catalyst for
the conjugate additions of organometallic compounds. However,
only a trace amount of the Heck-type reaction product 3a was de-
tected after 24 h in toluene (Table 1, entry 1). Since the presence of
water was crucial for some rhodium-catalyzed coupling reac-
tions,10,13 water was added as a cosolvent and the yield was in-
creased to 12% (entry 2).
Based on these initial results, a detailed optimization was car-
ried out. We found that a small amount of NiII(acac)2 was beneficial
to the reaction, and the yield was improved further from 24% to
72% after the addition of 10 mol % K2CO3 (entries 3 and 4). Other
bases such as Na2CO3 and cesium pivalate were also tested but
were not as effective as K2CO3 (entries 5–7). Fe, Co, and Cu salts
bearing acetylacetonate anion were also examined; only CoIII-
(acac)3 provided a moderate yield (entries 8–10). Notably, this
decarbonylative coupling occurred in a common solvent system
composed of toluene and water (15:1). Other solvent such as chlo-
robenzene, dichloroethane, and benzene lead to decreased yields
and 1,4-dioxane was not viable in this reaction (entries 11–14).
The substrate concentration was also examined and the best yield
was obtained when the concentration of the aldehyde was ca.
0.33 M (entries 4, 15 and 16). Finally, the relatively high reaction
R1
R1
R1
-CO
[Rh]
Ar
OR2
OR2
ArCHO
+
Ar
OR2
+
O
O
O
⇑
Corresponding author. Tel.: +1 514 398 8457; fax: +1 514 398 3797.
E-mail address: cj.li@mcgill.ca (C.-J. Li).
Scheme 1. Rhodium-catalyzed decarbonylative coupling reaction of aldehyde with
acrylate.
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.08.040

L. Yang et al. / Tetrahedron Letters 51 (2010) 5486–5489
5487
Table 1
Optimization for the Rh-catalyzed decarbonylative coupling reactiona
CHO
H3CO
H3CO
10 mol% [Rh], additive
base, solvent, O2, 24 h
OnBu
OnBu
+
OnBu
+
O
O
O
OCH3
1a
2a
4a
3a
Entry
Rh catalyst
Additive (mol %)
Base (mol %)
Solvent
Yield (%) 3a + 4a
Ratiob 3a/4a
1
2
3
4
5
6
7
8
(CO)2RhI(acac)
(CO)2RhI(acac)
(CO)2RhI(acac)
(CO)2RhI(acac)
(CO)2RhI(acac)
(CO)2RhI(acac)
(CO)2RhI(acac)
(CO)2RhI(acac)
(CO)2RhI(acac)
(CO)2RhI(acac)
(CO)2RhI(acac)
(CO)2RhI(acac)
(CO)2RhI(acac)
(CO)2RhI(acac)
(CO)2RhI(acac)
(CO)2RhI(acac)
(CO)2RhI(acac)
(CO)2RhI(acac)
(PPh)4RhIH
—
—
—
—
—
Toluene
Toluene + H2O
Toluene + H2O
5%
ND
ND
12%
24%
72%
63%
28%
24%
Trace
50%
22%
9%
NiII(acac)2 (20)
NiII(acac)2 (20)
NiII(acac)2 (20)
NiII(acac)2 (20)
NiII(acac)2 (20)
FeIII(acac)3 (20)
CoIII(acac)3 (10)
CuII(acac)3 (20)
NiII(acac)2 (20)
NiII(acac)2 (20)
NiII(acac)2 (20)
NiII(acac)2 (20)
NiII(acac)2 (20)
NiII(acac)2 (20)
NiII(acac)2 (20)
NiII(acac)2 (20)
NiII(acac)2 (20)
NiII(acac)2 (20)
60:40
65:35
56:44
41:59
62:38
ND
60:40
36:64
54:46
ND
66:34
67:33
56:44
73:27
44:56
ND
K2CO3 (10)
K2CO3 (20)
Na2CO3 (10)
CsOPiv (20)
K2CO3 (10)
K2CO3 (10)
K2CO3 (10)
K2CO3 (10)
K2CO3 (10)
K2CO3 (10)
K2CO3 (10)
K2CO3 (10)
K2CO3 (10)
K2CO3 (10)
K2CO3 (10)
K2CO3 (10)
K2CO3 (10)
Toluene + H2O
Toluene + H2O
Toluene + H2O
Toluene + H2O
Toluene + H2O
Toluene + H2O
Toluene + H2O
PhCl + H2O
9
10
11
12
13
14
15
16
17
18
19
20
Dioxane + H2O
DCE + H2O
0
45%
40%
63%
49%
16%e
14%f
23%
50%
Benzene + H2O
Toluene + H2Oc
Toluene + H2Od
Toluene + H2O
Toluene + H2O
Toluene + H2O
Toluene + H2O
34:66
55:45
(COD)2RhI(BF4)
a
b
c
d
e
f
Conditions: 1a (0.1 mmol), 2b (0.4 mmol), 10 mol % [Rh], additive, solvent (0.3 mL), H2O (0.02 mL), 150 °C, 24 h, under O2 atmosphere, unless otherwise noted.
Yields and the ratios were determined by 1H NMR analysis of the crude reaction mixture using an internal standard.
Toluene, 0.2 mL.
Toluene, 0.4 mL.
Reacted at 140 °C.
Reacted under argon.
temperature was important, decreasing the reaction temperature
gave a much lower yield (entries 4 and 18). Besides (CO)2RhI(acac),
this decarbonylative coupling reaction can also be catalyzed by
(PPh)4RhIH and (COD)2RhI(BF4), providing the target products in
23% and 50% total yields, respectively. It is worth noting that an ex-
cess of butyl methacrylate was required to serve as a sacrificial
hydrogen acceptor13c (Scheme 2, proposed mechanism).
Having established the standard reaction conditions, the sub-
strate scope of this novel decarbonylative coupling reaction was
explored. As shown by the results in Table 2, various aromatic
aldehydes reacted with butyl methacrylate 2a smoothly. Elec-
tron-rich aromatic aldehydes, with an alkoxyl or dimethylamino
substituent at the para-position, decarbonylatively coupled with
2a efficiently to furnish the corresponding Heck-type and conju-
gate addition products in 71% and 56% total yields, respectively
(Table 2, entries 1 and 2). 4-Phenylbenzaldehyde was also applica-
ble to this reaction and provided 3c and 4c in moderate yields (en-
try 3). Fluorinated aryl groups are highly useful building blocks in
biomedical studies.14 Thus, 4-fluoro benzaldehyde was tested and
low yields of the corresponding products were obtained (entry
4). Furthermore, both
a- and b-naphthaldehydes could take part
in this decarbonylative coupling reaction (entries 5 and 6). Under
the same reaction conditions, the decarbonylative coupling reac-
tion of aliphatic aldehydes such as hydrocinnaldehyde 1f and butyl
methacrylate were examined (entry 7), and only a trace amount of
the corresponding coupling products can be detected by GC–MS.
Apart from butyl methacrylate 2a, both ethyl methacrylate 2b
and tert-butyl acrylate 2c could also undergo decarbonylative cou-
pling with aromatic aldehyde smoothly, to give the corresponding
products (entries 7 and 8).
A tentative mechanism to explain the product formation is
illustrated in Scheme 2. First, low valent rhodium catalyst under-
goes oxidative addition with the aromatic aldehyde C–H bond to
produce acylrhodium hydride 5, which decarbonylates to give aryl-
rhodium hydride 6. Second, coordinated carbon monoxide is re-
placed by acrylate as a ligand to rhodium catalyst to form
complex 7. Subsequently, insertion of C@C into complex 7 gener-
ates 8, which undergoes reductive elimination to yield the conju-
gate addition product and regenerates the low valent rhodium
catalyst or b-hydride elimination to yield the Heck-type product
and rhodium complex 9. Rh(I) active catalyst is regenerated from
O
O
CO2R
or H2O
H
Ar
H
LRhI
Ar
Ar
RhIII
5
L
CO2R
or O2
L
H
L
CO2R
RhIII
OC Ar
RhIII
6
H
H
reductive
elimination
9
CO2R
Ar
CO2R
β-hydride
elimilation
CO
L
L
H
RhIII
RO2C
RhIII
Ar
RO2C
H
7
Ar
8
Scheme 2. Tentative mechanism for the rhodium-catalyzed decarbonylative cou-
pling reaction.

5488
L. Yang et al. / Tetrahedron Letters 51 (2010) 5486–5489
Table 2
Rh-Catalyzed decarbonylative coupling reaction of aldehydes with acrylatesa
10 mol% (CO)2RhI(acac)
R1
R1
R1
20 mol% Ni (acac)2
OR2
Ar
OR2
Ar
OR2
+
+
ArCHO
10 mol% K2CO3, O2, toluene
O
2a-c
O
4a-h
O
3a-h
1a-g
Entry
1
Aldehyde
Acrylate
Product
Yieldb (%)
MeO
MeO
OnBu
MeO
CHO
71
OnBu
OnBu
1a
2a
3a/4a = 65:35
O
3a
4a
O
O
(Me)2N
(Me)2N
(Me)2N
Ph
CHO
2
3
4
56
OnBu
3b
OnBu
4b
2a
2a
2a
1b
3b/4b = 82:18
O
O
Ph
F
Ph
F
CHO
51
OnBu
OnBu
1c
3c/4c = 74:26
3c
4c
O
O
O
F
CHO
38
OnBu
OnBu
1d
3d/4d = 70:30
3d
4d
O
CHO
OnBu
OnBu
5
73
2a
3e/4e = 87:13
3e
O
O
4e
1e
CHO
CHO
OnBu
OnBu
6
7
63
2a
2a
3f/4f = 60:40
O
3f
O
4f
1f
—
—
Trace
1g
MeO
MeO
OEt
2b
8
9
54
OEt
OEt
4g
1a
1a
O
O
3h/4h = 60:40
O
O
O
O
3g
OtBu
2c
MeO
MeO
52
OtBu
3h
OtBu
4h
3h/4h = 65:35
a
Conditions15: 1 (0.2 mmol), 2 (0.8 mmol), 10 mol % (CO)2RhI(acac), 20 mol % Ni(acac)2, 10 mol % K2CO3, toluene (0.6 mL), H2O (0.04 mL), 150 °C, 24 h, under O2
atmosphere.
b
Isolated yields after flash silica gel chromatograph and the ratios were determined by 1H NMR analysis of the crude reaction mixture.
complex 9 assisted by the excessive acrylate13c or dioxygen. Alter-
natively, the activation of aldehyde and subsequent decarbonyla-
tion were catalyzed by rhodium and the arylrhodium hydride 6
undergoes transmetalation to produce the corresponding arylnick-
el species to take part in the Heck-type reaction and conjugate
addition reaction.
In conclusion, we have discovered the first decarbonylative
Heck-type reaction and conjugate addition of aldehyde with unsat-
urated carbonyl compounds. Efforts to increase the efficiency of
the reaction as well as to further tune the reaction into selective
Heck-type or conjugate addition is undergoing in our laboratory.
fellowships (Bill and Christina Chan Fellowship and Principle’s
Graduate Fellowship).
References and notes
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We thank the Canada Research Chair (Tier 1) foundation (to
CJL), CFI, FQRNT and NSERC for their support of our research.
C.A.C. would also like to thank McGill University for post-graduate

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5489
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following: An oven-dried reaction vessel was charged with 4-methoxybenz-
aldehyde 1a (29.8 mg, 0.2 mmol), butyl methacrylate 2a (0.8 mmol, 114 mg,
4 equiv), (CO)2RhI(acac) (5.1 mg, 0.02 mmol, 10 mol %) and Ni(acac)2 (10.2 mg,
0.04 mmol, 20 mol %), K2CO3 (2.8 mg, 0.02 mmol, 10 mol %), vacuumed, and
refilled with argon. Then toluene (0.6 mL) and water (0.04 mL) were added by
syringe and the vessel was sealed and heated at 150 °C (oil bath temperature).
After 24 h, the resulting mixture was cooled to rt, transferred to silica gel
column directly, and eluted with hexanes and ethyl acetate (95:5) to give pure
products 3a and 4a.
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Compound 3a: oil; 1H NMR (500 MHz, CDCl3, TMS) d (ppm) 7.63 (s, 1H), 7.38
(d, J = 9.0 Hz, 2H), 6.92 (d, J = 9.0 Hz, 2H), 4.21 (t, J = 6.5 Hz, 2H), 3.84 (s, 3H),
2.13 (s, 3H), 1.68–1.73 (m, 2H), 1.41–1.49 (m, 2H), 0.97 (t, J = 7.5 Hz, 3H); 13C
NMR (75 MHz, CDCl3, TMS) d (ppm) 169.2, 159.8, 138.5, 131.7, 130.1, 114.0,
113.9, 64.9, 55.5, 31.0, 19.5, 14.3, 14.0. HRMS (ESI) m/z: [M+1]+ calcd for
C15H21O3, 249.1485; found: 249.1480.
Compound 4a: oil; 1H NMR (500 MHz, CDCl3, TMS) d (ppm) 7.08 (d, J = 8.5 Hz,
2H), 6.81 (d, J = 8.5 Hz, 2H), 4.03 (t, J = 6.5 Hz, 2H), 3.78 (s, 3H), 2.95 (dd, J = 7.0,
13.0 Hz, 1H), 2.59–2.70 (m, 2H), 1.51–1.57 (m, 2H), 1.28–1.33 (m, 2H), 1.14 (d,
J = 6.5 Hz, 3H), 0.90 (t, J = 7.5 Hz, 3H); 13C NMR (75 MHz, CDCl3, TMS) d (ppm)
176.5, 158.3, 131.6, 128.7, 126.7, 64.4, 55.4, 42.0, 39.1, 30.8, 19.3, 17.0, 13.9.
HRMS (ESI) m/z: [M+1]+ calcd for C15H23O3, 251.1642; found: 258.1635.