Rhodium-catalyzed reductive allylation of conjugated aldehydes with allyl acetate

Article abstract of DOI:10.1021/jo902706p

Reductive allylation of aryl and alkenyl aldehydes with allyl acetate catalyzed by the ionic diamine carbonyl rhodium complex, [Rh(TMEDA)(CO) ₂][RhCl₂(CO)₂], under a carbon monoxide atmosphere afforded the corresponding homoallylic alcohols in good isolated yields.

Full text of DOI:10.1021/jo902706p

pubs.acs.org/joc
of reductants (e.g., SnCl2) assisting in the formation of a
Rhodium-Catalyzed Reductive Allylation of
Conjugated Aldehydes with Allyl Acetate
transition metal allyl complex.4 The excellent Lewis acid-free
alternatives to these methods are described in recent reports
on ruthenium-catalyzed nucleophilic carbonyl allylation5a-c
and enantioselective iridium-catalyzed carbonyl allylation
with allyl acetate.6 To our knowledge, the only report on
Rh-catalyzed carbonyl allylation with allyl alcohol involves
the use of more than a stoichiometric amount of SnCl2.7
We, therefore, initiated research to address the rhodium-
catalyzed allylation of carbonyls to determine whether the
reaction is possible with allyl acetate under Lewis acid-free
conditions.
Maksym Vasylyev and Howard Alper*
Centre for Catalysis Research and Innovation, Department of
Chemistry, University of Ottawa, 10 Marie Curie, Ottawa,
Ontario, Canada K1N 6N5
howard.alper@uottawa.ca
Received December 22, 2009
We now describe a rhodium-catalyzed Lewis acid-free
reductive allylation of conjugated aldehydes using allyl
acetate as a source of the allyl group, furnishing the corre-
sponding homoallylic alcohols in good isolated yields.
In our initial experiment, the allylation reaction of ben-
zaldehyde 1a was carried out with the [Rh(COD)Cl]2 cata-
lyst, potassium iodide, and 2 equiv of allyl acetate 2 under
35 bar of carbon monoxide in THF at 120 °C and gave none
of the desired 1-phenylbuten-1-ol 3a (Table 1, entry 1).
TABLE 1. Reductive Allylation of Benzaldehyde by Use of
[Rh(COD)Cl]2/KI as the Catalytic System
Reductive allylation of aryl and alkenyl aldehydes with
allyl acetate catalyzed by the ionic diamine carbonyl
rhodium complex, [Rh(TMEDA)(CO)2][RhCl2(CO)2],
under a carbon monoxide atmosphere afforded the cor-
responding homoallylic alcohols in good isolated yields.
Cs2CO3
(equiv)
2
(equiv)
t
(h)
T
(°C)
conversion
(mol %)a
yield
(mol %)a
entry
b
1
2
3
4
2
2
2
4
24
24
72
48
120
120
100
100
-
48
84d
87d
94d
A typical carbonyl allylation reaction is usually stoichio-
metric in nature and involves the use of allyl boron, allyl
silane, or allyl metal reagents (e.g., allyl tin), which are either
not simple to prepare, moisture and air sensitive (e.g., allyl
Mg or Li), or toxic.1 Some of the available catalytic methods
such as Umani-Ronchi-Keck2 or Lewis base-catalyzed
allylation3 also require similar types of reagents. It is quite
apparent, therefore, that a catalytic method that employs
readily available allyl alcohol or its corresponding acetate as
a source of the allyl fragment is more desirable. On the other
hand, most of the existing methods for catalytic allylation
with palladium or nickel catalysts and allyl alcohol or allyl
acetate require the use of more than stoichiometric amounts
1
0.6
0.6
75
80 (74)c
aDetermined by GC. bNo reaction occurred. cIsolated yield after
purification by column chromatography. dAccompanied by some un-
identified products.
However, addition of 1 equiv of an inorganic base, cesium
carbonate, resulted in the formation of 3a in 48% conversion
and 84% selectivity (Table 1, entry 2). Carrying out the
reaction with 0.6 equiv of Cs2CO3 at 100 °C for 72 h afforded
3a in 75% conversion and 87% selectivity (Table 1, entry 3).
The use of 4 equiv of allyl acetate decreased the reaction time
from 72 to 48 h and the reaction occurred affording slightly
higher conversion than that realized when effecting the
reaction with 2 equiv of 2 (Table 1, entry 3 vs 4).
To determine whether the nature of the base has any
influence on the reaction, and to investigate the possibility
of decreasing the reaction time to 24 h with no loss in
conversion and selectivity, we carried out the allylation
(1) For excellent reviews on the subject see: (a) Denmark, S. E.; Almstead,
N. G. In Modern Carbonyl Chemistry; Otera, J., Ed.; Wiley-VCH: Weinheim,
Germany, 2000; Chapter 10, pp 299-402; (b) Rouch, W. R. In Comprehensive
Organic Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon Press: Oxford, UK,
1991; Vol. 2, Chapter 1.1, p 1. (c) Yamamoto, Y.; Asao, N. Chem. Rev. 1993, 93,
2207.
(2) Costa, A. L.; Piazza, M. G.; Tagliavini, E.; Trombini, C.; Umani-
Ronchi, A. J. Am. Chem. Soc. 1993, 115, 7001.
(3) Denmark, S. E.; Fu, J. J. Am. Chem. Soc. 2001, 123, 9488.
(4) See for example: (a) Masuyama, Y.; Takahara, J. P.; Kurusu, Y.
J. Am. Chem. Soc. 1988, 110, 4473. (b) Masuyama, Y.; Ito, T.; Tachi, K.; Ito,
A.; Kurusu, Y. Chem. Commun. 1999, 1261. (c) Hirashita, T.; Kambe, S.;
Tsuji, H.; Omori, H.; Araki, S. J. Org. Chem. 2004, 69, 5054. (d) Jang, T.-S.;
Keum, G.; Kang, S.-B.; Chung, B.-Y.; Kim, Y. Synthesis 2003, 5, 775.
(e) Fontana, G.; Lubineau, A.; Scherrmann, M.-C. Org. Biomol. Chem. 2005,
3, 1375. (f) Masuyama, Y.; Hayashi, R.; Otake, K.; Kurusu, Y. J. Chem. Soc.,
Chem. Commun. 1988, 44. (g) Kimura, M.; Tomizawa, T.; Horino, Y.;
Tanaka, S.; Tamaru, Y. Tetrahedron Lett. 2000, 41, 3627.
(5) (a) Tsuji, Y.; Mukai, T.; Kondo, T.; Watanabe, Y. J. Organomet.
Chem. 1989, 369, C51. (b) Kondo, T.; Ono, H.; Satake, N.; Mitsudo, T.-a.;
Watanabe, Y. Organometallics 1995, 14, 1945. (c) Denmark, S. E.; Nguyen,
S. T. Org. Lett. 2009, 11, 781.
(6) (a) Kim, I. S.; Ngai, M.-Y.; Krische, M. J. J. Am. Chem. Soc. 2008,
130, 6340. (b) Kim, I. S.; Ngai, M.-Y.; Krische, M. J. J. Am. Chem. Soc. 2008,
130, 14891.
(7) Masuyama, Y.; Kaneko, Y.; Kurusu, Y. Tetrahedron Lett. 2004, 45,
8969.
2710 J. Org. Chem. 2010, 75, 2710–2713
Published on Web 03/16/2010
DOI: 10.1021/jo902706p
r
2010 American Chemical Society

Vasylyev and Alper
JOCNote
TABLE 2. Investigation of the Influence of the Base on the Allylation of
Benzaldehyde Effected by the [Rh(COD)Cl]2/KI Catalytic System
TABLE 4. Optimization of the Allylation Reaction Conditions
t
(h)
conversion
(mol %)a
80(74)b
85
yield
(mol %)a
yield
(mol
%)a
88c
95c
93c
91c
92c
entry
base (equiv)
catalyst
(mol %)
Cs2CO3
(equiv)
CO
(bar)
conversion
(mol %)a
77(65)b
92(87)b
90
1
2
3
4
5
6
7
Cs2CO3 (0.6)
Cs2CO3 (2)
SrCO3 (2)
K2CO3 (2)
KHCO3 (2)
Ba(OH)2 (2)
DBU (2)
48
48
24
24
24
24
24
94
91
entry
c
1
2
3
4
5
5
5
7.5
7.5
7.5
0.6
1
1.25
1.25
1.25
35
10
35
20
10
-
56
37
62d
64d
c
98
95
-
-
c
aDetermined by GC. bIsolated yield after purification by column
aDetermined by GC. bIsolated yield after purification by column
chromatography. cAccompanied by some unidentified products.
chromatography. No reaction occurred. dAccompanied by some un-
identified products.
c
TABLE 5. Rh-Catalyzed Allylation of Aromatic Aldehydesa
TABLE 3. Allylation of Benzaldehyde Catalyzed by Different Rh
Complexes
yield
(mol
%)a
94d
85d
80d
69d
73d
88d
entry
product
Ar
isolated yield (%)
conversion
(mol %)a
entry
Rh source (mol %)
t (h)
1
2
3
4
5
6
7
8
9
3a
3b
3c
3d
3e
3f
3g
3h
3i
Ph
87
80
83
85
62
88
92
83
77
89
78
4-methylphenyl
4-isopropylphenyl
2-methoxyphenyl
2-methylphenyl
2-chlorophenyl
2-bromophenyl
4-bromophenyl
4,40-biphenyl
1
2
3
4
5
6
[Rh(COD)Cl]2 (5)b
RhCl(PPh3)3(CO) (5)
RhCl(PPh3)3 (5)
[Rh(COD)]OTf (5)
[Rh(dppb)(COD)][BF4] (5)
[Rh(TMEDA)(CO)2]
[RhCl2(CO)2] (5)
48
24
24
24
24
24
80(74)c
50
60
48
36
77(65)c
f
7
[Rh(TMEDA)(CO)2]
[RhCl2(CO)2] (5)e
24
-
11
12
3j
3k
naphthyl
4-carbamoylphenyl
aDetermined by GC. bKI (15 mol %). cIsolated yield after purification
by column chromatography. dAccompanied by some unidentified pro-
ducts. eN2 (35 bar) was used instead of CO. fNo reaction occurred.
aReaction conditions: substrate, 2 mmol; [Rh(TMED)(CO)2][RhCl2-
(CO)2], 5 mol % ; Cs2CO3 nH2O, 2 mmol; allyl acetate, 8 mmol; THF,
10 mL; CO, 10 bar; 100 °C.
3
reaction in the presence of a range of bases. As the results in
Table 2 show, the use of SrCO3, Ba(OH)2, and DBU was not
effective for the production of 3a (Table 2, entries 3, 6, and 7);
on the other hand, the use of K2CO3 and KHCO3 produced
3a in low conversion and selectivity (Table 2, entries 4 and 5).
When the allylation reaction was carried out with 2 equiv of
Cs2CO3 for 48 h, 3a was formed in slightly higher conversion
(Table 2, entry 2).
Although the allylation of benzaldehyde can be effected
in 48 h with the conditions outlined in Table 1, entry 4,
we thought that we could shorten the reaction time by using
a complex other than the initially chosen [Rh(COD)Cl]2 as
the catalyst. The influence of the rhodium source on the
allylation of benzaldehyde was tested by employing several
Rh(I) complexes listed in Table 3. The results presented
in Table 3 indicate that the most effective catalyst for
the reaction was the ionic diamine carbonyl rhodium com-
plex, [Rh(TMEDA)(CO)2]þ[Rh(Cl)2(CO)2]-, which gave
conversions and selectivities similar to those obtained with
[Rh(COD)Cl]2 for a shorter reaction time of 24 h (Table 3,
entry 6 vs entry 1). Allylation carried out under N2 instead of
CO gave no product. It is evident, therefore, that although
the carbon monoxide fragment does not appear in the
reaction product, the presence of CO is necessary for the
reaction.
The reaction conditions outlined in Table 3, entry 6, were
further optimized by varying the catalyst and the base
concentration, and by changing the pressure of CO. The
results in Table 4 indicate that the most optimal conditions
are those presented in entry 2, affording 1-phenylbuten-1-ol
3a in 92% conversion, 95% selectivity, and 87% isolated
yield.
Using the optimal reaction conditions, a range of aryl
aldehydes were tested for the allylation reaction. The results
presented in Table 5 demonstrate that substrates 1a-d and
1f-k afford the corresponding homoallylic alcohols 3a-d
and 3f-k in good isolated yields. 1-(2-Methylphenyl)buten-
1-ol 3e was isolated in a somewhat lower yield of 62%. The
location and the nature of the halogen substituent have
little effect on the performance of the reaction (Table 5,
entries 6-8).
To determine whether the Rh-catalyzed reductive allyla-
tion reaction can be extended to R,β-unsaturated aldehydes,
J. Org. Chem. Vol. 75, No. 8, 2010 2711

Vasylyev and Alper
JOCNote
TABLE 6. Reductive Allylation of Alkenyl Aldehydes
SCHEME 1. The Suggested Mechanism for Rh-Catalyzed
Allylation
t
(h)
conversion
(mol %)a
yield
(mol %)a
entry
solvent
1b
2b
3b
4b
5b
6e
THF
THF
THF
benzene
acetonitrile
[CH3(CH2)13P(C6H13)3]PF6
24
72
96
24
24
24
60
78
85
95
91
53c
d
-
41
38c
f
d
-
aDetermined by GC. bR = H. cSelectivity decreased due to the oxy-
Cope rearrangement of 5a. dNo reaction occurred. eR = Me. fCYPHOS
IL 110.
TABLE 7. Reductive Allylation of Alkenyl Aldehydesa
formation of a Rh-acyl intermediate. Generation of propene
indicated a competing hydrolytic decomposition of Rh(III)
allyl as a side reaction.8 Allylation of 1a in the presence of
D2O (2 mmol) gave nondeuterated product 3a and 2H-
enriched propene.9
Taking into account the aforementioned results, we pro-
pose a mechanism for the Rh-catalyzed allylation reaction
with allyl acetate (Scheme 1). Generated Rh(III) allyl com-
plex 710 reacts with aldehyde in a Barbier-type fashion7
through an intermediate 9 to form alkoxy-Rh(III) complex
10, which then undergoes hydrolysis;11 subsequent reduction
of hydroxy-Rh(III) complex 12 by CO regenerates the
catalyst 6.
In conclusion, a variety of aryl and alkenyl aldehydes
undergo allylation by allyl acetate, using the ionic diamine
carbonyl rhodium complex, [Rh(TMEDA)(CO)2]þ[Rh(Cl)2-
(CO)2]-, under carbon monoxide to give the corresponding
homoallylic alcohols in good isolated yields.
entry
product
R1
R2
isolated yield (%)
1
2
3
5a
5b
5c
H
H
4-t-Bu
H
Me
Me
79
85
69
aReaction conditions: substrate, 2 mmol; [Rh(TMEDA)(CO)2]-
[RhCl2(CO)2], 5 mol %; Cs2CO3 nH2O, 2 mmol; allyl acetate, 8 mmol;
THF, 10 mL; CO, 10 bar; 110 °C.
3
cinnamaldehyde 4a was reacted under conditions suitable
for the alkylation of aryl aldehydes. The results summarized
in Table 6 show that allylation of cinnamaldehyde 4a re-
quired higher temperatures and longer reaction times than
those needed for aryl aldehydes 1a-k. At the same time,
reaction times longer than 72 h led to a decrease in selectivity
due to the oxy-Cope rearrangement of the homoallylic
alcohol 5a into the corresponding aldehyde (Table 6,
entry 3). The use of benzene, acetonitrile, and phosphorus-
based ionic liquid as the reaction solvents was also tested
(Table 6, entries 4-6).
As one can see from the results, no product was formed
during the reaction conducted in benzene and the phospho-
nium ionic liquid (Table 6, entries 4 and 6). In acetonitrile the
oxy-Cope rearrangement proceeded faster than that in THF
(Table 6, entry 5 vs entry 1). On the basis of the results shown
in Table 6, we can conclude that the optimal conditions for
the reductive allylation of cinnamaldehyde are these found in
Table 6, entry 2.
Using the optimal conditions, substituted cinnamalde-
hydes were evaluated for the alkylation reaction. The results
presented in Table 7 demonstrate that substrates 4a-c afford
the corresponding homoallylic alcohols 5a-c in good iso-
lated yields.
To gain an insight into the mechanism of the reaction, we
conducted an experiment using benzaldehyde-1-d (8). Iso-
lation of 11 with retention of deuterium label excludes
Experimental Section
General Procedure for the Rhodium-Catalyzed Reductive Al-
lylation of Aryl Aldehydes with Allyl Acetate. A glass liner
containing the substrate (2 mmol), [Rh(TMEDA)(CO)2]-
[RhCl2(CO)2] (5 mol %), Cs2CO3 nH2O (2 mmol), allyl
3
acetate (8 mmol), and THF (10 mL) was placed in a 45 mL
autoclave equipped with a magnetic stirring bar. The auto-
clave was flushed three times with carbon monoxide and
then pressurized to 10 bar.12 The autoclave was placed in
(8) Propene was trapped as 1,2-dibromopropane by slowly passing
the gas mixture through a solution of Br2 in CHCl3; an excess of Br2
was removed by treating the solution with aq Na2SO3. 1,2-Dibromo-
propane was detected by GC-MS analysis (m/z 202 ([Mþ] 2%),
123 (97), 121 (100), 107 (4), 105 (4), 95 (5), 93 (6), 81 (5), 78 (5)). Forma-
tion of propene explains the need for an excess of allyl acetate for the
reaction.
(9) See the Supporting Information, pp S49 and S50.
(10) See for example: (a) Payne, M. J.; Cole-Hamilton, D. J. J. Chem.
Soc., Dalton Trans. 1997, 3167. (b) Hayashi, T.; Okada, A.; Suzuka, T.;
Kawatsura, M. Org. Lett. 2003, 5, 1713.
(11) Cs2CO3 contained 1.96% of H2O (determined by TGA); water may
be produced during the reaction from H2CO3 generated by trapping AcOH
with Cs2CO3. Regeneration of 0.5 equiv of H2O and entrapment of AcOH
define the role of Cs2CO3 in the reaction.
(12) Carbon monoxide is a highly poisonous gas; please see the Support-
ing Information for the safety requirements.
2712 J. Org. Chem. Vol. 75, No. 8, 2010

Vasylyev and Alper
JOCNote
Acknowledgment. We are grateful to the National Sciences
and Engineering Research Council for support of the research.
an oil bath preset to 100 °C on a stirring hot plate. After
24 h, the autoclave was removed from the oil bath and
cooled to room temperature prior to the release of CO
gas. The reaction mixture was concentrated in vacuum,
and the residue was purified by flash chromatography with
use of 20% ethyl acetate in hexanes as eluant to afford
the product.
Supporting Information Available: Experimental proce-
1
dures and copies of H and 13C NMR spectra of synthesized
compounds. This material is available free of charge via the
Internet at http://pubs.acs.org.
J. Org. Chem. Vol. 75, No. 8, 2010 2713