Direct allylic substitution of allyl alcohols by carbon pronucleophiles in the presence of a palladium/carboxylic acid catalyst under neat conditions

Article abstract of DOI:10.1016/j.tetlet.2004.02.094

The reaction of allylic alcohols with carbon pronucleophiles in the presence of the Pd(PPh₃)₄/carboxylic acid combined catalytic system, under neat conditions (without an organic solvent or without water as the solvent) enabled the direct allylation of the pronucleophiles, giving the corresponding allylated products in high yields.

Full text of DOI:10.1016/j.tetlet.2004.02.094

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 3101–3103
Direct allylic substitution of allyl alcohols by carbon
pronucleophiles in the presence of a palladium/carboxylic
acid catalyst under neat conditions
Nitin T. Patil and Yoshinori Yamamoto*
Department of Chemistry, Graduate School of Science, Tohoku University, Aramaki, Aoba-ku, Sendai 980-8578, Japan
Received 12 December 2003; revised 11 February 2004; accepted 18 February 2004
Abstract—The reaction of allylic alcohols with carbon pronucleophiles in the presence of the Pd(PPh3)4/carboxylic acid combined
catalytic system, under neat conditions (without an organic solvent or without water as the solvent) enabled the direct allylation of
the pronucleophiles, giving the corresponding allylated products in high yields.
Ó 2004Elsevier Ltd. All rights reserved.
Palladium catalysed allylic alkylation of active methyl-
ene compounds such as b-ketoesters and malonates (the
Tsuji–Trost reaction) is a reliable and widely used
method for C–C bond formation.1 In general, the
method involves the use of allylic acetates, carbonates,
halides, phosphates, NR2 etc.2 However, the direct use
of allylic alcohols is not well exploited because of the
poor capability of the hydroxyl group to serve as a good
leaving group.3 Some efforts have been made in this
direction by the use of activators, which coordinate with
the hydroxyl group thereby increasing its leaving group
ability.4 As a part of our continuing interest on palla-
dium catalysed C–C bond formation, we recently re-
ported an entirely different approach, using the
hydrocarbonation of alkynes in the presence of the
Pd(PPh3)4/carboxylic acid combined catalytic system,5
which serves as an alternative allylation procedure to the
existing methods. While researching the applicability of
this combined catalytic system, we found that heating a
mixture of cinnamyl alcohol with 1.2 equiv of diethyl
malonate in the presence of Pd(PPh3)4 (5 mol %) and
acetic acid (10 mol %) in 1,4-dioxane at 100 °C gave the
monoallylated product in excellent yield. While the
work was in progress in our laboratory, a similar report
appeared in the literature6 based on the same concept in
which the authors studied several acid sources and
concluded that 1-adamantanecarboxylic acid (1-Ad-
COOH) and lauric acid in water were the best. We were
excited with these results as they may open a new insight
into palladium chemistry in water. The novelty of the
concept led us to test the ability of this catalytic system
in an iterative fashion. Unfortunately, during these
studies, we found that in the present reaction there is no
need for a specific carboxylic acid or water as a solvent;
the direct allylation of pronucleophiles 1 with allylic
alcohols 2 takes place, without an organic solvent and
without water as the solvent, in the presence of a cata-
lytic amount of Pd(PPh3)4/carboxylic acid under neat
conditions (Eq. 1).
Pd(PPh )
RCOOH
neat
3 4
EWG
1
EWG
1
1
1
H O
+
+
2
H
OH
R
R
EWG
2
EWG
2
1
3
2a R = Ph
1
1
2b R = H
ð1Þ
In one set of experiments, we carried out the reaction of
dibenzoylmethane with cinnamyl alcohol with
Pd(PPh3)4 and 1-AdCOOH in water at 70 °C for 30 min
as per the literature procedure (Table 1, entry 1). A
similar result was obtained with lauric acid as an addi-
tive in water (entry 2). In another experiment, the same
reaction was performed with acetic acid and benzoic
acid as the additive under neat conditions at 70 °C for
Keywords: Palladium catalyst; Allylic substitution; p-Allylpalladium
complex; Pronucleophile; Water; Palladium carboxylic acid catalyst;
Allylic alcohol.
* Corresponding author. Tel.: +81-22-217-6581; fax: +81-22-217-6784;
e-mail addresses: yoshi@yamamoto1.chem.tohoku.ac.jp; tl@
yamamoto1.chem.tohoku.ac.jp
0040-4039/$ - see front matter Ó 2004Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.02.094

3102
N. T. Patil, Y. Yamamoto / Tetrahedron Letters 45 (2004) 3101–3103
Table 1. Effect of carboxylic acids on Pd-catalysed allylic substitution of 2a with 1a
Pd(PPh3)4 (2 mol%)
RCOOH (10 mol%)
OH
O
COPh
COPh
+
Ph
OH
Ph
Ph
Ph
neat
1a
2a
3a
Entry
Acid
Solvent
Conditions
Yielda
1
1-AdCOOH
Lauric acid
Acetic acid
Water
Water
Neat
70 °C, 30 min
70 °C, 30 min
70 °C, 30 min
°C, 30 min
30
30
2
3
4Benzoic acid
31
28
Neat
70
5
6
7
1-AdCOOH
Acetic acid
Acetic acid
Neat
Neat
70 °C, 30 min
100 °C, 30 min
100 °C, 12 h
33
95(91)b
98(90)b
1,4-Dioxane
a NMR yield.
b Isolated yield.
30 min (entries 3 and 4). The rates of these two sets of
1
reactions (followed by H NMR) were found to be al-
under neat conditions. It is reasonable that the acid
having a more hydrophobic7 nature tends to remain in
the organic phase and hence catalyses the reaction more
effectively. On the other hand, a hydrophilic acid tends
to remain in the water at high temperatures and is not
available for the reaction in the organic phase hence the
reaction rate is slow. Although the authors of Ref. 6
reported the reaction in water, the reaction must pro-
ceed in the organic phase because neither the catalyst
nor substrate is soluble in water. Some representative
examples of direct allylic alkylation using Pd(PPh3)4/
acetic acid under neat conditions are summarised in
Table 2.
most identical. With 1-AdCOOH as the additive, the
reaction also proceeded at the same rate under neat
conditions (entry 5). As shown in entry 6, the reaction
was heated to 100 °C in the presence of acetic acid to
obtain full conversion. The reaction proceeded well in
an organic solvent such as 1,4-dioxane however it took
longer (entry 7). The above observations unequivocally
confirmed that there was no specific role for either water
as a solvent or a particular carboxylic acid. Although
Kobayashi et al. studied several carboxylic acids and
found that 1-AdCOOH or lauric acid gave the best re-
sult in water, the experimental results obtained in our
laboratory are quite different. Perhaps, the difference is
due to whether the reaction was carried out in water or
After standardisation of the catalytic system we then
applied this catalytic system to various pronucleophiles.
Table 2. Pd(PPh3)4/acetic acid catalysed allylic substitution of allyl alcohols with C-nucleophiles under neat conditions
Entry
1
1
2
Pd(PPh3)4 (mol%)
2
Conditions
Product 3
Yielda (%)
81
1a
2b
80 °C/30 min
3b
COOEt
COOEt
2
3
4
5
6
7
8
1b
1c
1d
2a
2b
2a
2b
2a
2b
2a
5
5
2
2
5
5
5
100 °C/10 min
100 °C/10 min
80 °C/1.5 h
80 °C/1.5 h
100 °C/2 h
3c
3d
3e
3f
95
61b
95
63c
98
94
85
1b
COPh
SO2Ph
1c
COPh
COOEt
3g
3h
3i
1d
100 °C/2 h
COPh
100 °C/5 h
COOEt
1e
O
O
9
1f
2a
0.5
80 °C/30 min
3j
71d
O
O
O
10
2a
2b
2
2
100 °C/10 min
80 °C/15 min
3k
3l
98
96
COOEt
1g
11
1g
a Isolated yield.
b 30% of diallylated product was isolated.
c 21% of diallylated product was isolated.
d Yield refers to diallylated product.

N. T. Patil, Y. Yamamoto / Tetrahedron Letters 45 (2004) 3101–3103
3103
Chichester, 1995, pp 290–340; (d) Consiglio, G.; Way-
mouth, R. M. Chem. Rev. 1989, 89, 257–276; (e) Frost, C.
G.; Howarth, J.; Williams, J. M. J. Tetrahedron: Asymme-
try 1992, 3, 1089–1122; (f) Trost, B. M.; Vranken, D. L. V.
Chem. Rev. 1996, 96, 395–422; (g) Trost, B. M. Acc. Chem.
Res. 1996, 29, 355–364; (h) For recent references, see
Commandeur, C.; Thorimbert, S.; Malacria, M. J. Org.
Chem. 2003, 68, 5588–5592; (i) Kawamura, M.; Kiyotake,
R.; Kudo, K. Chirality 2002, 14, 724–726; For ruthenium
catalysed allylic alkylation, See: Trost, B. M.; Fraisse, P. L.;
Ball, Z. T. Angew. Chem. Int. Ed. 2002, 41, 1059–1061; For
Iridium catalysed allylic substitution with phenoxide, see:
Lopez, F.; Ohmura, T.; Hartwig, J. F. J. Am. Chem. Soc.
2003, 125, 3426–3427, and references cited therein.
As shown in entry 1, allylation of dibenzoylmethane 1a
with allyl alcohol 2b proceeded smoothly to give the
monoallylated adduct 3b in good yield. The monoallyl-
ation of diethyl malonate with cinnamyl alcohol also
proceeded smoothly to give 3c in excellent yield. How-
ever, when allyl alcohol was employed as the substrate,
monoallylated product 3d was isolated in 61% yield with
the formation of the diallylated product in 30% yield.
The reaction of 1c and 1d with cinnamyl alcohol and
allyl alcohol gave the corresponding monoallylated
products in good yields (entries 4–7). However the less
reactive substrate 1e took 5 h for the completion of the
reaction (entry 8). In the case of MeldrumÕs acid 1f,
diallylated product 3j was obtained (entry 9). The five-
membered cyclic b-keto ester 1g on reaction with 2a and
2b gave the products 3k and 3l, respectively, in excellent
yields (entries 10–11).
2. Tsuji, J. Transition Metal Reagents and Catalysts; Wiley:
New York, 2000; Chapter 4.
3. For Ir catalysed allylic substitution, see: (a) Takeuchi, R.;
Kashio, M. Angew. Chem. Int. Ed. 1997, 36, 263–265; (b)
Takeuchi, R.; Kashio, M. J. Am. Chem. Soc. 1998, 120,
8647–8655; For Ni catalysed allylic substitution, see: (c)
Buckwalter, B. L.; Burfitt, I. R.; Felkin, H.; Joly-Goudket,
M.; Naemura, K.; Salomon, M. F.; Wenkert, E.; Wovku-
lich, P. M. J. Am. Chem. Soc. 1978, 100, 6445–6450; (d)
Consiglio, G.; Piccolo, O.; Roncetti, L.; Morandini, F.
Tetrahedron 1986, 42, 2043–2053.
In conclusion, we have discovered that the palladium
catalysed allylic substitution of pronucleophiles with
allyl alcohols proceeds under neat conditions. We have
also shown that there is no need for water as a solvent8
or a long-chain fatty acid; even acetic acid works well
for the present reaction.
4. For inorganic acids such as As2O3 see: (a) Lu, X.; Lu, L.;
Sun, J. J. Mol. Cat. 1987, 41, 245–251; (b) B2O3, see: Lu,
X.; Jiang, X.; Tao, X. J. Organomet. Chem. 1988, 344, 109–
118; (c) CO2, see: Sakamoto, M.; Shimizu, I.; Yamamoto,
A. Bull. Chem. Soc. Jpn. 1996, 69, 1065–1078; For another
example, see: Ozawa, F.; Okamoto, H.; Kawagishi, S.;
Yamamoto, S.; Minami, T.; Yoshifuji, M. J. Am. Chem.
Soc. 2002, 124, 10968–10969, and references cited therein.
5. For hydrocarbonation of alkynes, see: Kadota, I.; Shibuya,
A.; Gyoung, Y. S.; Yamamoto, Y. J. Am. Chem. Soc. 1998,
120, 10262–10263; For hydroamination of alkynes, see (a)
Kadota, I.; Shibuya, A.; Lutete, M. L.; Yamamoto, Y. J.
Org. Chem. 1999, 64, 4570–4571; (b) Lutete, M. L.; Kadota,
I.; Shibuya, A.; Yamamoto, Y. Heterocycles 2002, 58, 347–
357; (c) For hydroalkoxylation of alkynes, see: Kadota, I.;
Lutete, M. L.; Shibuya, A.; Yamamoto, Y. Tetrahedron
Lett. 2001, 42, 6207–6210; We have also shown the use of
the Pd(0)/CH3COOH combined catalytic system for the
hydroamination of allenes, see: Al-Masum, M.; Meguro,
M.; Yamamoto, Y. Tetrahedron Lett. 1997, 38, 6071–6074.
6. Manabe, K.; Kobayashi, S. Org. Lett. 2003, 5, 3241–3244.
7. Water–octanol partition coefficients, log Poct, have been
used to indicate hydrophobicity of organic compounds, for
example, log Poct for lauric acid: 4.6, acetic acid: )0.13, see:
Sangster, J. J. Phys. Chem. Ref. Data 1989, 18, 1111.
8. The present reaction conditions, the allylation under neat
conditions, produced 1 equiv of water after completing the
reaction. It is not clear at present whether the water
generated during the reaction progress is essential or not for
promoting the allylation. All we can say here is that water is
not needed as a solvent.
General procedure for the allylation of pronucleophiles
with allyl alcohols. The preparation of 3a is representa-
tive. To a mixture of dibenzoylmethane 1a (200 mg,
0.90 mmol) and cinnamyl alcohol 2a (188 mg,
1.34mmol) were added Pd(PPh 3)4 (52 mg, 0.046 mmol)
and acetic acid (6 mg, 0.090 mmol) and the mixture was
heated at 100 °C for 30 min. The gummy material thus
obtained was purified through a short column of silica
gel using hexane/EtOAc ¼ 9:1 as a eluent to give 3a
(275 mg) in 91% yield.
Acknowledgements
N.T.P. thanks JSPS for a postdoctoral research fellow-
ship.
References and notes
1. For recent reviews, see: (a) Godleski, S. In Comprehensive
Organic Synthesis; Trost, B. M., Fleming, I., Eds.; Perg-
amon: New York, 1991; 4, pp 585–661; (b) Davies, J. A. In
Comprehensive Organometallic Chemistry II; Wilkinson, G.,
Stone, F. G. A., Abel, E. W., Eds.; Pergamon: Oxford,
UK, 1995; 9, pp 291–390; (c) Tsuji, J. Palladium Reagents
and Catalysts. Innovations in Organic Synthesis; John Wiley: