Heck-type benzylation of olefins with benzyl trifluoroacetates

Article abstract of DOI:10.1246/cl.2004.348

A new synthetic method for 1-aryl-2-alkenes from 1-olefins by benzylation treating with benzyl trifluoroacetates using palladium-catalyst is developed on the basis of oxidative addition of benzyl carboxylates to Pd(0) complexes to give benzyl(carboxylato)palladium(II) complexes with cleavage of benzyl-oxygen bond.

Full text of DOI:10.1246/cl.2004.348

348
Chemistry Letters Vol.33, No.3 (2004)
Heck-type Benzylation of Olefins with Benzyl Trifluoroacetates
Hirohisa Narahashi, Akio Yamamoto, and Isao Shimizuꢀ
Department of Applied Chemistry, Graduate School of Science and Engineering, Waseda University,
3-4-1 Ohkubo, Shinjuku-ku, Tokyo 169-8555
(Received December 11, 2003; CL-031220)
A new synthetic method for 1-aryl-2-alkenes from 1-olefins
benzylpalladium complex 210 reacted with ethyl acrylate to yield
ethyl (E)-4-phenyl-2-butenoate (3) (Scheme 2).
Furthermore, the reaction using benzyl trifluoroacetates was
developed to catalytic olefin benzylation.
by benzylation treating with benzyl trifluoroacetates using palla-
dium-catalyst is developed on the basis of oxidative addition of
benzyl carboxylates to Pd(0) complexes to give benzyl(carbox-
ylato)palladium(II) complexes with cleavage of benzyl–oxygen
bond.
O
Ph
OEt
O
(Ph2MeP)2Pd
DMF, 100 oC, 24 h
OCOCF3
OEt
Over the last years, the Heck reaction has been widely used
as a mild and efficient method for the regioselective attachment
of side chains to aromatic rings or benzyl groups.1 In general, a
wide variety of organic halides such as aryl halides, aroyl hal-
ides, and benzyl halides2 have been utilized. Besides organic hal-
ides aromatic triflates and alkenyl triflates obtained form phenols
or enolates can be also used.1 Goossen3 and De Vries4 utilized p-
nitrophenyl benzoic acid esters and acid anhydride as non-halide
aryl sources, respectively, which enable to avoid using stoichio-
metric amounts of base and the resulting salt production, provid-
ing a clean reaction. However, benzylation of olefins using non-
halogen benzyl compounds was scarcely reported since oxida-
tive addition of benzyl carboxylates hardly proceeds with normal
benzyl esters.
Palladium-catalyzed allylation of nucleophiles utilizing the
C–O bond cleavage in allylic carboxylates and carbonates has
been extensively used in organic synthesis, on the other hand
the utility of benzyl carboxylates has been much less explored
despite the expected propensity benzyl compounds having the
allylic nature to add oxidatively to Pd(0) complex.5 We have
been concerned with transition metal-catalyzed C–O bond clea-
vages in oxygen-containing organic compounds and their appli-
cation to development of molecular catalysts for organic synthe-
sis. So far with utilization of the C–O bond cleavage processes
we have developed useful new processes to convert carboxylic
anhydrides and carboxylic acids into aldehydes and ketones.6–8
On the continuous efforts to develop possibility of C–O activa-
tion with transition metal complexes, we have found that oxida-
tive addition of benzyl trifluoroacetates takes place with ease,
which is applied to catalytic benzylation of olefins.
3
2
25 %
Scheme 2.
Table 1 shows the conversion of ethyl acylate on reaction
with benzyl trifluoroacetate in the presence of Pd catalyst into
3 as the product of olefin benzylation process under various con-
ditions.
The catalytic reaction at 100–120 ꢁC afforded the benzyla-
tion product in good yields (Runs 3, 4, and 11). When the reac-
tion was carried out at higher temperature, 120 and 140 ꢁC, the
double bond isomerization took place to give ethyl (E)-4-phen-
yl-3-butenoate (4) in addition to 3 (Runs 11 and 12). The thermal
isomerizaion in the absence of palladium catalysts was observed
in an experiment of heating 3 in DMF at 130 ꢁC for 24 h to give
the isomer 4 in 83% yield along with the starting 3 (16%).
The catalyst system composed Pd(OAc)2 and 4 equiv. of
PPh3 and DMF as solvent was most effective, affording a variety
Table 1. Palladium-catalyzed benzylation of ethyl acrylate
O
OEt
OEt
OEt
5 mol% Pd cat.
Ph
Ph
+
Ph
OR
DMF, temp., 24 h
3
4
O
O
(R = CF3CO)
Entry
Pd cat.
temp/ꢁC yield (3 + 4)/%a 3/4b
1
2
3
Pd(OAc)2
100
100
100
100
100
100
100
100
100
80
0
-
Pd(OAc)2 + 2 PPh3
45
61
75
0
1:0
1:0
1:0
-
Pd(OAc)2 + 4 PPh3
4c Pd(OAc)2 + 4 PPh3
Cleavage benzyl C–O bond of benzyl trifluoroacetate on in-
teraction with tertiary phosphine-coordinate Pd(0) has been re-
ported (Scheme 1).9
Olefin insertion reaction from readily obtained benzyl (tri-
fluoroacetato)palladium(II) complex was expected. In fact, the
5
6
7
8
9
Pd(OAc)2 + 4 P(o-tolyl)3
Pd(OAc)2 + 4 P(n-Bu)3
Pd(dba)2 + 4 PPh3
Pd(OAc)2 + dppp
Pd(PPh3)4
55
60
0
1:0
1:0
-
49
31
68
48
1:0
1:0
1:1
1:5
L
L
Ph
O
+
Ph
10 Pd(OAc)2 + 4 PPh3
11 Pd(OAc)2 + 4 PPh3
12 Pd(OAc)2 + 2 PPh3
Pd
L2Pd
acetone, r.t., 3 h
OCOCF3
F3C
O
120
140
Ph
(L = PMePh2)
1
2
a Isolated yield. b The distribution of isomers 3 and 4 was determined
by 1H NMR analysis of the mixture of 3 and 4. c Reaction time was
39.5 h.
93%
Scheme 1.
Copyright Ó 2004 The Chemical Society of Japan

Chemistry Letters Vol.33, No.3 (2004)
349
of benzylation products. The results by treating various olefins
with benzyl trifluoroacetates in DMF at 100 ꢁC for 39 h were
summarized in Table 2.11
The catalytic benzylation of olefins from benzyl alcohols was
developed using trifluoroacetic anhydride. These methods pro-
vide a useful tool for preparation of various aromatic compounds
as a non-halogen method.
Table 2. The palladium-catalyzed benzylation of olefins with
benzyl trifluoroacetates
References and Notes
5 mol% Pd(OAc)2
20 mol% PPh3
DMF, 100 oC, 39 h
1
J. Tsuji, ‘‘Palladium Reagents and Catalysts—Innovations in
Organic Synthesis,’’ Wiley, Chichester, UK (1995).
a) G. Z. Wu, F. Lamaty, and E. Negishi, J. Org. Chem., 54,
2507 (1989). b) G. Z. Wu, I. Shimoyama, and E. Negishi, J.
Org. Chem., 56, 6506 (1991). c) Y. Pan, Z. Zhang, and H.
Hu, Synth. Commun., 22, 2019 (1992). d) Y. Pan, X. Jiang,
and H. Hu, Tetrahedron Lett., 41, 725 (2000).
R
Ar
R
+
Ar
OCOCF3
2
R'
R'
Entry
Ar
R
R0 Yield/%
1
2
Ph
COOEt
H
H
H
H
H
H
H
Ph
H
H
H
75
59
65
42
81
80
27
21
56
69
56
p-MeOC6H4
Ph
COOEt
3
4
5
L. Goossen and J. Paetzold, Angew. Chem., Int. Ed., 41, 1237
(2002).
3
p-MeC6H4
p-MeC6H4
p-MeC6H4
p-MeC6H4
2-pryridine
Ph
4
p-MeOC6H4
p-ClC6H4
p-FC6H4
Ph
M. S. Stephan, A. J. J. M. Teunissen, G. K. M. Verzijl, and
J. G. de Vries, Angew. Chem., Int. Ed., 37, 662 (1998).
Nucleophilic substitution using benzyl carbonates and esters
of naphthylmethanols was reported. a) R. Kuwano, Y.
Kondo, and Y. Matsuyama, J. Am. Chem. Soc., 125, 12104
(2003). b) J.-Y. Legros, M. Toffano, and J.-C. Fiaud,
Tetrohedron, 51, 3235 (1995).
a) K. Nagayama, I. Shimizu, and A. Yamamoto, Bull. Chem.
Soc. Jpn., 74, 1803 (2001). b) R. Kakino, H. Narahashi, I.
Shimizu, A. Yamamoto, Chem. Lett., 2001, 1242. c) R.
Kakino, H. Narahashi, I. Shimizu, A. Yamamoto, Bull.
Chem. Soc. Jpn., 75, 1333 (2002). d) A. Yamamoto, R.
Kakino, and I. Shimizu, Helv. Chim. Acta, 2001, 2996.
R. Kakino, I. Shimizu, and A. Yamamoto, Bull. Chem. Soc.
Jpn., 74, 371 (2001).
5
6
7
8
p-MeOC6H4
p-MeOC6H4
9
p-ClC6H4
p-MeC6H4
10
11
2,4,6-trimethyphenyl
3,5,6-trimethoxyphenyl p-MeC6H4
6
The present process is applicable to various benzyl trifluo-
roacetates with olefins and is tolerant to a variety of functional
groups. Benzyl trifluoroacetates having functional groups such
as methoxy, chloro, and fluoro groups at the para position can
be catalytically converted into the corresponding compounds
in good yields. The benzylation can be also preformed with ole-
fins such as 2-vinylpyridine, 4-methyl, 4-chlorostyrene, and 1, 1-
diphenylstyrene.
We have previously observed that treatment of carboxylic
acids with less reactive carboxylic anhydride such as pivalic an-
hydride or dimethyl dicarbonate leads to the anhydride mixture,
which can be subjected to the C–O bond cleavage process to
yield aldehydes or ketones. Under a similar concept, we attempt-
ed the direct benzylation of olefins from benzyl alcohols. In fact,
treatment of p-methoxybenzyl alcohol with p-methyl styrene at
100 ꢁC in DMF in the presence of trifluoroacetic anhydride (3
equiv.) and Pd catalyst for 24 h gave 5 in 42% yield (Scheme 3).
In conclusion, a practical method to convert olefins into ar-
yl-2-alkenes by treating benzyl trifluoroacetates with olefins is
developed on the basis of oxidative addition of benzyl carboxy-
lates to Pd(0) complexes to give benzyl(carboxylato)palladiu-
m(II) complexes with cleavage of benzyl–oxygen bond, which
does not require the use of benzyl chlorides or any extra base.
7
8
a) A. Yamamoto, Adv. Organomet. Chem., 34, 111 (1992). b)
Y. S. Lin and A. Yamamoto, ‘‘Topics in Organometallic
Chemistry,’’ ed. by S. Murai, Springer, Berlin (1999), Vol. 3.
K. Nagayama, I. Shimizu, and A. Yamamoto, Bull. Chem.
Soc. Jpn., 72, 799 (1999).
9
10 Synthesis of the complex 2 in this paper is as follows. To a
mixture of acetone (5 mL) trans-[PdEt2(PMePh2)2]
(1.66 mmol) and styrene (5.24 mmol) were added at
ꢂ20 ꢁC. On standing the mixture at 50 ꢁC for 2 h, the solu-
tion became a homogeneous yellow solution. After cooling
this solution at room temperature, benzyl trifluoroacetate
(2.02 mmol) was added to this solution and the solution
was stirred at room temperature for 3 h. After the reaction
mixture was concentrated, hexane was added to precipitate
2, which was filtrated and collected. Subsequent washing
with hexane and drying in vacuo gave a pale white powder
of 2 (1.54 mmol, 93% yield).
11 General procedure for the reactions in Table 2 is as follows.
A DMF solution (5 mL) of benzyl trifluoroacetate (1 mmol),
olefin (1.2 mmol), Pd(OAc)2 (0.05 mmol) and PPh3
(0.20 mmol) was placed in a 25-mL-Schlenk tube. The solu-
tion was stirred at 100 ꢁC for 39 h. On cooling the mixture,
ethyl acetate and water were added and the aqueous layer
was extracted with ethyl acetate. The organic layer was dried
over MgSO4 and the solvent was evaporated in vacuo. Puri-
fication of the residue by column chromatography (hexane/
ethyl acetate) gave the benzylation compound.
3.0 eq. (CF3CO)2O
5 mol% Pd(OAc)2
OH
20 mol% PPh3
+
DMF, 100 oC, 39 h
MeO
1.0 eq.
1.2 eq.
5
MeO
42 %
Scheme 3.
Published on the web (Advance View) February 23, 2004; DOI 10.1246/cl.2004.348