Suzuki cross-coupling reaction of benzylic halides with arylboronic acids in the presence of a tetraphosphine/palladium catalyst

Article abstract of DOI:10.1055/s-2003-40994

The cis,cis,cis-1,2,3,4-tetrakis(diphenylphosphinomethyl) cyclopentane-[PdCl(C₃H₅)]₂ system catalyses efficiently the Suzuki cross-coupling reaction of benzylic halides with arylboronic acids. A wide variety of benzylic bromides or chlorides and functionalised arylboronic acids lead selectively to the corresponding diarylmethane adducts in good yields. Furthermore, this catalyst can be used at low loading in many cases.

Full text of DOI:10.1055/s-2003-40994

1668
LETTER
Suzuki Cross-Coupling Reaction of Benzylic Halides with Arylboronic Acids
in the Presence of a Tetraphosphine/Palladium Catalyst
S
uzuki Cross-C
u
oupling Rea
d
ction of
B
enz
o
ylic Halide
s
vic Chahen, Henri Doucet,* Maurice Santelli*
Laboratoire de Synthèse Organique associé au CNRS, Faculté des Sciences de Saint Jérôme, Avenue Escadrille Normandie-Niemen,
13397 Marseille Cedex 20, France
Fax +33(491)983865; E-mail: henri.doucet@univ.u-3mrs.fr; E-mail: m.santelli@univ.u-3mrs.fr
Received 26 May 2003
ene derivatives by Pd-catalysed coupling of various aryl-
Abstract: The cis,cis,cis-1,2,3,4-tetrakis(diphenylphosphinometh-
boronic acids with allylic acetates has also been de-
yl) cyclopentane–[PdCl(C3H5)]2 system catalyses efficiently the
Suzuki cross-coupling reaction of benzylic halides with arylboronic
scribed.5
acids. A wide variety of benzylic bromides or chlorides and func-
The nature of the phosphine ligand has an important effect
tionalised arylboronic acids lead selectively to the corresponding
on the rate of transition metal-catalysed reactions. In order
diarylmethane adducts in good yields. Furthermore, this catalyst
to find more efficient palladium catalysts, we have pre-
can be used at low loading in many cases.
pared the tetrapodal6 phosphine ligand, tedicyp7,8
Key words: catalysis, palladium, tetraphosphine, arylboronic ac-
(Figure 1). We have reported recently several results ob-
ids, benzylic halides
tained in Suzuki cross-coupling using tedicyp as ligand.9
For example, a TON (turnover number) of 96 000 000 for
the reaction of 4-bromobenzophenone with phenylboron-
Diarylmethane derivatives are fundamental building
ic acid has been obtained.9b We have also reported some
blocks in organic synthesis and their preparation is an im-
results using tedicyp ligand with sterically hindered aryl
portant industrial goal. The palladium-catalysed so-called
bromides,9d heteroaryl bromides,9c aryl chlorides,9e
Suzuki cross-coupling reaction should be a powerful
vinylhalides9g and with a variety of arylboronic acids.9f
method for the synthesis of such compounds.1 Organobo-
Here, in order to further establish the requirements for a
ron reagents exhibit greater functional group compatibili-
successful Suzuki cross-coupling reaction, we wish to
ty than organozinc or Grignard reagents. Moreover, the
report the reaction of benzylic halides with a variety of
innocuous nature of boronic acids, which are generally
arylboronic acids using tedicyp as the ligand.
non-toxic and thermally, air-, and moisture-stable, is a
practical advantage of the Suzuki reaction, relative to the
other coupling processes. However, the procedure suffers
Ph2P
PPh2
PPh2
Ph2P
Tedicyp
generally from high catalyst loading due to the fast de-
composition of the catalyst. In recent years, several ther-
mally stable palladium catalysts have been successfully
used for Suzuki reactions,2 but most of the results, which
have been described with these catalysts, were obtained
for the coupling of aryl halides. With these catalysts, rel-
atively few results have been reported for the coupling of
benzylic halides. Most of the results were described with
the popular but unstable catalyst Pd(PPh3)4.3,4 Recently,
an alternative procedure for the synthesis of 3-arylprop-1-
Figure 1
For this study, based on previous results,9 xylene was
chosen as the solvent and potassium carbonate as the base
(Scheme 1). The reactions were performed at 130 °C un-
der argon in the presence of a ratio 1/2 of [Pd(C3H5)Cl]2/
tedicyp as catalyst.
R2
X
[Pd(C3H5)Cl]2, Tedicyp,
xylenes, K2CO3, 130 °C, 20 h
R1
(HO)2B
R1
R2
+
X = Cl, Br
R1 = H, Me, F, Cl, NO2, CF3, CN, CO2Me
R2 = H, Me, F, MeO, NO2, CHO, CF3, COMe
Scheme 1
Synlett 2003, No. 11, Print: 02 09 2003. Web: 05 08 2003.
Art Id.1437-2096,E;2003,0,11,1668,1672,ftx,en;G11903ST.pdf.
DOI: 10.1055/s-2003-40994
© Georg Thieme Verlag Stuttgart · New York

LETTER
Suzuki Cross-Coupling Reaction of Benzylic Halides with Arylboronic Acids
1669
First, we have investigated the Suzuki cross-coupling re- the reaction with sterically congested arylboronic acids
action with benzyl bromide The reaction with phenylbo- such as 2-methyl-, 2-methoxy-, 2-acetyl- or 2,4,6-tri-
ronic acid can be performed with as little as 0.0001% methylphenylboronic acids. With these substrates, the
catalyst (entries 1 and 2). Using similar conditions, in ab- coupling products were obtained with TONs of 84 000, 56
sence of catalyst, most of the benzylbromide was recov- 000, 910 and 810, respectively (entries 12–18).
ered unreacted and the formation of a mixture of side
Next, we studied the influence of the substituents on the
products which seems to contain traces of diphenyl-
benzylic bromides. Electron-withdrawing groups at the
methane was observed. Then the reaction with several
aryl have a minor influence on the reaction rates. 4-Ni-
para-, meta- and ortho-substituted arylboronic acids in
trobenzyl bromide, 4-trifluoromethylbenzyl bromide, 4-
the presence of catalyst was examined. The results pre-
cyanobenzyl bromide, methyl 3-(bromomethyl)benzoate
sented in the Table 1 show a strong influence of the sub-
and 3-chlorobenzyl bromide with phenylboronic acid led
stituents at the arylboronic acids on the reaction rate,
to the corresponding disubstituted methanes in the pres-
however this influence does not come from the electronic
ence of 0.01–0.0001% catalyst (entries 21, 30, 33, 42 and
factors on the arylboronic acid: in the presence of 4-meth-
44). The ortho-substituted 2-fluorobenzyl bromide also
oxy or 4-fluorophenylboronic acids the reactions required
gave the expected adduct in high TON: 83 000 (entry 45).
0.001–0.0001% catalyst (entries 3–7). Higher catalyst
On the other hand, the sterically hindered 2-methylbenzyl
loadings were required for arylboronic acids containing
bromide led to a much slower reaction. With this substrate
functional groups such as nitro, formyl or acetyl (entries
a TON of 910 was obtained (entry 46). In a few cases the
8–10 and 15). The lower reaction rates observed with
formation of a side product resulting from the homocou-
these functionalised arylboronic acids probably does not
pling of the benzylic bromide was also observed (entries
comes from the transmetallation rate of the arylboronic
23 and 26).
acid with the palladium catalyst, but more likely, from
poisoning of the catalyst by the impurities or the function-
al groups of these arylboronic acids.9f Then, we studied
Table 1 Palladium-Tedicyp Catalysed Suzuki Cross-Coupling Reactions with Benzylic Bromides (Scheme 1)10,11,a
Entry
R-Br
Arylboronic acid
Ratio
Yield (%)b
substrate/catalyst
1
2
Benzyl bromide
Benzyl bromide
Phenylboronic acid
Phenylboronic acid
100000
1000000
99 (91)
58
3
4
5
Benzyl bromide
Benzyl bromide
Benzyl bromide
4-Methoxyphenylboronic acid
4-Methoxyphenylboronic acid
4-Methoxyphenylboronic acid
1000
10000
100000
100 (88)
63
30
6
7
Benzyl bromide
Benzyl bromide
4-Fluorophenylboronic acid
4-Fluorophenylboronic acid
100000
1000000
100 (82)
40
8
Benzyl bromide
3-Nitrophenylboronic acid
100
74 (60)
9
10
Benzyl bromide
Benzyl bromide
3-Formylphenylboronic acid
3-Formylphenylboronic acid
250
1000
100 (74)
45
11
12
Benzyl bromide
Benzyl bromide
3,5-Bistrifluoromethylphenylboronic acid
2-Methylphenylboronic acid
10000
89 (77)
100000
100 (84)
13
14
Benzyl bromide
Benzyl bromide
2-Methoxyphenylboronic acid
2-Methoxyphenylboronic acid
10000
100000
81
56
15
Benzyl bromide
2-Acetylphenylboronic acid
1000
100 (91)
16
17
Benzyl bromide
Benzyl bromide
2,4-Difluorophenylboronic acid
2,4-Difluorophenylboronic acid
1000
10000
100 (85)
70
18
19
Benzyl bromide
Benzyl bromide
2,4,6-Trimethylphenylboronic acid
Thiophene-2-boronic acid
1000
250
87 (81)
62 (55)
20
21
4-Nitrobenzyl bromide
4-Nitrobenzyl bromide
Phenylboronic acid
Phenylboronic acid
100000
1000000
100 (78)
87
22
23
4-Nitrobenzyl bromide
4-Nitrobenzyl bromide
4-Methoxyphenylboronic acid
4-Methoxyphenylboronic acid
1000
10000
100 (84)
74c
Synlett 2003, No. 11, 1668–1672 © Thieme Stuttgart · New York

1670
L. Chahen et al.
LETTER
Table 1 Palladium-Tedicyp Catalysed Suzuki Cross-Coupling Reactions with Benzylic Bromides (Scheme 1)10,11,a (continued)
Entry
R-Br
Arylboronic acid
Ratio
Yield (%)b
substrate/catalyst
24
25
4-Nitrobenzyl bromide
4-Nitrobenzyl bromide
3-Nitrophenylboronic acid
3-Formylphenylboronic acid
1000
100 (79)
86 (64)
250
26
27
4-Nitrobenzyl bromide
4-Nitrobenzyl bromide
2,4-Difluorophenylboronic acid
2,4-Difluorophenylboronic acid
250
1000
100 (80)d
85
28
29
4-Nitrobenzyl bromide
4-Nitrobenzyl bromide
2-Methoxyphenylboronic acid
2-Methoxyphenylboronic acid
1000
10000
100 (92)
66
30
4-Trifluoromethylbenzyl bromide
Phenylboronic acid
100000
94 (87)
31
32
4-Trifluoromethylbenzyl bromide
4-Trifluoromethylbenzyl bromide
4-Methoxyphenylboronic acid
4-Methoxyphenylboronic acid
1000
10000
100
49
33
34
4-Cyanobenzyl bromide
4-Cyanobenzyl bromide
Phenylboronic acid
10000
1000
100 (86)
100 (84)
4-Fluorophenylboronic acid
35
36
4-Cyanobenzyl bromide
4-Cyanobenzyl bromide
4-Methoxyphenylboronic acid
4-Methoxyphenylboronic acid
1000
10000
100 (81)
68
37
38
4-Cyanobenzyl bromide
4-Cyanobenzyl bromide
3-Nitrophenylboronic acid
3-Nitrophenylboronic acid
250
1000
100 (75)
85
39
40
4-Cyanobenzyl bromide
4-Cyanobenzyl bromide
2-Methoxyphenylboronic acid
2-Methoxyphenylboronic acid
1000
10000
100 (92)
63
41
42
Methyl 3-(bromomethyl)benzoate
Methyl 3-(bromomethyl)benzoate
Phenylboronic acid
Phenylboronic acid
10000
100000
100 (95)
85
43
44
45
46
Methyl 3-(bromomethyl)benzoate
3-Chlorobenzyl bromide
2-Fluorobenzyl bromide
2-Acetylphenylboronic acid
Phenylboronic acid
1000
100000
100000
1000
100 (88)
90 (85)
89 (83)
98 (91)
Phenylboronic acid
2-Methylbenzyl bromide
Phenylboronic acid
a Conditions: catalyst, see ref.7, RBr (1 equiv), arylboronic acid (2 equiv), K2CO3 (2 equiv), xylene, 130 °C, 20 h, GC or NMR yields.
b Yields in parentheses are isolated.
c 20% of homocoupling of 4-nitrobenzylbromide was also observed.
d 12% of homocoupling of 4-nitrobenzylbromide was also observed.
Then, we studied the Suzuki cross-coupling reaction with tries 13 and 15). Finally, 1,4-bis(chloromethyl)benzene
benzylic chlorides. As illustrated in Table 2, in all cases with phenylboronic acid gave the expected diaddition
much slower reactions rates were observed than with ben- adduct: 1,4-dibenzylbenzene, however, with this substrate
zylic bromides. With these benzylic chlorides the rate-de- a low TON was observed (entry 16).
termining step seems to be the oxidative addition to the
In summary, we have established that the tedicyp-palladi-
palladium complex. The reaction of benzyl chloride with
um system is not limited to Suzuki reactions of aryl ha-
phenylboronic acid led to the coupling adduct with a TON
lides; benzylic halides are also efficiently coupled. In the
of 470 (entries 1 and 2). Similar reactions rates were ob-
presence of the tedicyp/palladium complex, the Suzuki re-
served in the presence of substituted arylboronic acids.
action of benzylic halides including the couplings of chlo-
For example, TONs of 580 and 230 were obtained in the
rides with a wide variety of arylboronic acids can be
presence of 4-methoxyphenylboronic acid and 2-
performed with as little as 0.0001% catalyst. Due to the
acetylphenylboronic acid (entries 4 and 6). As expected, a
high price of palladium, the practical advantage of such
lower TON was obtained in the presence of the sterically
low catalyst loadings can become increasingly important
congested 2,4,6-trimethylphenylboronic acid (entry 8). In
for industrial processes. The functional group tolerance is
the presence of functionalised benzyl chlorides, similar
remarkable, substituents such as fluoro, methyl, methoxy,
results were obtained indicating a minor influence of elec-
acetyl, nitro, formyl, cyano or ester are tolerated. As ex-
tronic factors at the benzyl chlorides on the reaction rates
pected, both the steric hindrance of the benzylic halides
(entries 9-15). For example, 4-methoxybenzyl chloride
and the steric hindrance of the boronic acids have an effect
and 3,5-dinitrobenzyl chloride in the presence of phenyl-
on the reaction rates.
boronic acid led to very similar TONs of 610 and 840 (en-
Synlett 2003, No. 11, 1668–1672 © Thieme Stuttgart · New York

LETTER
Suzuki Cross-Coupling Reaction of Benzylic Halides with Arylboronic Acids
1671
Table 2 Palladium-Tedicyp Catalysed Suzuki Cross-Coupling Reactions with Benzylic Chlorides (Scheme 1)10,a
Entry
R-Cl
Arylboronic acid
Ratio
Yield (%)b
substrate/catalyst
1
2
Benzyl chloride
Benzyl chloride
Phenylboronic acid
Phenylboronic acid
250
1000
100 (91)
47
3
4
Benzyl chloride
Benzyl chloride
4-Methoxyphenylboronic acid
4-Methoxyphenylboronic acid
250
1000
92 (87)
58
5
6
7
8
Benzyl chloride
Benzyl chloride
Benzyl chloride
Benzyl chloride
2,4-Difluorophenylboronic acid
2-Acetylphenylboronic acid
250
250
250
100
55 (52)
100 (92)
75 (72)
45 (41)
2-Methoxyphenylboronic acid
2,4,6-Trimethylphenylboronic acid
9
10
4-Fluorobenzyl chloride
4-Fluorobenzyl chloride
Phenylboronic acid
Phenylboronic acid
250
1000
100 (95)
56
11
12
13
4-Nitrobenzyl chloride
4-Nitrobenzyl chloride
4-Methoxybenzyl chloride
Phenylboronic acid
1000
1000
1000
100 (83)
100 (80)c
87 (61)
4-Methoxyphenylboronic acid
Phenylboronic acid
14
15
3,5-Dinitrobenzyl chloride
3,5-Dinitrobenzyl chloride
Phenylboronic acid
Phenylboronic acid
250
1000
100 (93)
84
16
a,a¢-Dichloro-p-xylene
Phenylboronic acid
100
60 (54)d
a Conditions: catalyst, see ref.7, RCl (1 equiv), arylboronic acid (2 equiv), K2CO3 (2 equiv), xylene, 130 °C, 20 h, GC or NMR yields.
b Yields in parentheses are isolated.
c 7% of homocoupling of 4-nitrobenzylchloride was also observed.
d Phenylboronic acid: 3 equivalents.
(3) For examples of Suzuki reactions with benzylic halides:
(a) Sharp, M. J.; Snieckus, V. Tetrahedron Lett. 1985, 26,
5997. (b) Pernia, G. J.; Kilburn, J. D.; Essex, J. W.;
Mortishire-Smith, R. J.; Rowley, M. J. Am. Chem. Soc.
1996, 118, 10220. (c) Chowdhury, S.; Georghiou, P. E.
Tetrahedron Lett. 1999, 40, 7599. (d) Juteau, H.; Gareau,
Y.; Labelle, M.; Sturino, C. F.; Sawyer, N.; Tremblay, N.;
Lamontagne, S.; Carrière, M.-C.; Denis, D.; Metters, K. M.
Bioorg. Med. Chem. 2001, 9, 1977. (e) Botella, L.; Najera,
C. Angew. Chem. Int. Ed. 2002, 41, 179.
(4) For examples of Suzuki reactions with ethyl bromoacetate or
cinnamyl bromide derivatives, see: (a) Moreno-Manas, M.;
Pajuelo, F.; Pleixats, R. J. Org. Chem. 1995, 60, 2396.
(b) Cortes, J.; Moreno-Manas, M.; Pleixats, R. Eur. J. Org.
Chem. 2000, 239. (c) Gooßen, L. J. Chem. Commun. 2001,
669. (d) Liu, X.-X.; Deng, M.-Z. Chem. Commun. 2002,
622.
Acknowledgement
We thank CNRS and the ‘Conseil Général des Bouches-du-Rhône,
Fr’ for the financial support.
References
(1) For reviews on the palladium-catalysed Suzuki cross-
coupling reactions see: (a) Miyaura, N.; Suzuki, A. Chem.
Rev. 1995, 95, 2457. (b) Suzuki, A. J. Organomet. Chem.
1999, 576, 147. (c) Suzuki, A. J. Organomet. Chem. 2002,
653, 83. (d) Littke, A. F.; Fu, G. C. Angew. Chem. Int. Ed.
2002, 41, 4176.
(2) (a) Beller, M.; Fischer, H.; Herrmann, W. A.; Öfele, K.;
Brossmer, C. Angew. Chem., Int. Ed. Engl. 1995, 34, 1848.
(b) Albisson, D. A.; Bedford, R. B.; Lawrence, S. E.; Scully,
P. N. Chem. Commun. 1998, 2095. (c) Weissman, H.;
Milstein, D. Chem. Commun. 1999, 1901. (d) Wolfe, J. P.;
Buchwald, S. L. Angew. Chem., Int. Ed. 1999, 38, 2413.
(e) Wolfe, J. P.; Singer, R. A.; Yang, B. H.; Buchwald, S. L.
J. Am. Chem. Soc. 1999, 121, 9550.
(5) For examples of coupling of arylboronic acids with
allylacetate, see: Bouyssi, D.; Gerusz, V.; Balme, G. Eur. J.
Org. Chem. 2002, 2445.
(6) For a review on the synthesis of polypodal
diphenylphosphine ligands, see: Laurenti, D.; Santelli, M.
Org. Prep. Proced. Int. 1999, 31, 245.
(7) Laurenti, D.; Feuerstein, M.; Pèpe, G.; Doucet, H.; Santelli,
M. J. Org. Chem. 2001, 66, 1633.
(8) Feuerstein, M.; Doucet, H.; Santelli, M. J. Org. Chem. 2001,
66, 5923.
Synlett 2003, No. 11, 1668–1672 © Thieme Stuttgart · New York

1672
L. Chahen et al.
LETTER
76.62, H 4.71; MS (EI, 70 eV) m/z (%): 204(100) [M+];
(9) (a) Feuerstein, M.; Laurenti, D.; Bougeant, C.; Doucet, H.;
Santelli, M. Chem. Commun. 2001, 325. (b) Feuerstein, M.;
Laurenti, D.; Doucet, H.; Santelli, M. Synthesis 2001, 2320.
(c) Feuerstein, M.; Doucet, H.; Santelli, M. Tetrahedron
Lett. 2001, 42, 5659. (d) Feuerstein, M.; Doucet, H.;
Santelli, M. Tetrahedron Lett. 2001, 42, 6667.
Table 1 (entry 18): d = 7.25–7.10 (m, 3 H, Ph), 7.01 (d, J =
7.2 Hz, 2 H, Ph), 6.89 (s, 2 H, Ar), 4.02 (s, 2 H, CH2), 2.29
(s, 3 H, Me), 2.20 (s, 6 H, Me); Table 1 (entry 25): d = 9.96
(s, 1 H, CHO), 8.14 (d, J = 8.7 Hz, 2 H, Ar), 7.85–7.35 (m,
4 H, Ar), 7.33 (d, J = 8.7 Hz, 2 H, Ar), 4.14 (s, 2 H, CH2);
C14H11NO3 (214.2): calcd. C 69.70, H 4.60; found C 70.01,
H 4.72; MS (EI, 70 eV) m/z (%): 241(100) [M+]; Table 1
(entry 26): d = 8.12 (d, J = 8.7 Hz, 2 H, Ar), 7.34 (d, J = 8.7
Hz, 2 H, Ar), 7.11 (m, 1 H, Ar), 6.82 (m, 2 H, Ar), 4.03 (s, 2
H, CH2); C13H9F2NO2 (249.2): calcd. C 62.65, H 3.64; found
C 62.52, H 3.74; MS (EI, 70 eV) m/z (%): 249(100) [M+];
Table 1 (entry 28): d = 8.08 (d, J = 8.6 Hz, 2 H, Ar), 7.32 (d,
J = 8.6 Hz, 2 H, Ar), 7.25 (m, 1 H, Ar), 7.09 (d, J = 7.3 Hz,
1 H, Ar), 6.89 (m, 2 H, Ar), 4.03 (s, 2 H, CH2), 3.77 (s, 3 H,
Me); Table 1 (entry 35): d = 7.60 (d, J = 7.8 Hz, 2 H, Ar),
7.29 (d, J = 7.8 Hz, 2 H, Ar), 7.10 (d, J = 8.5 Hz, 2 H, Ar),
6.88 (d, J = 8.5 Hz, 2 H, Ar), 4.00 (s, 2 H, CH2), 3.82 (s, 3
H, Me); Table 1 (entry 39): d = 7.53 (d, J = 7.3 Hz, 2 H, Ar),
7.28 (d, J = 7.3 Hz, 2 H, Ar), 7.23 (m, 1 H, Ar), 7.07 (d, J =
7.4 Hz, 1 H, Ar), 6.87 (m, 2 H, Ar), 4.00 (s, 2 H, CH2), 3.78
(s, 3 H, Me); Table 1 (entry 43): d = 7.83 (m, 1 H, Ar), 7.79
(s, 1 H, Ar), 7.67 (d, J = 7.6 Hz, 1 H, Ar), 7.39 (t, J = 7.6 Hz,
1 H, Ar), 7.30 (m, 3 H, Ar), 7.20 (d, J = 7.6 Hz, 1 H, Ar), 4.31
(s, 2 H, CH2), 3.86 (s, 3 H, Me), 2.46 (s, 3 H, Me); C17H16O3
(268.3): calcd. C 76.10, H 6.01; found C 75.87, H 6.21; MS
(EI, 70 eV); m/z (%): 268(36) [M+].
(e) Feuerstein, M.; Doucet, H.; Santelli, M. Synlett 2001,
1458. (f) Feuerstein, M.; Berthiol, F.; Doucet, H.; Santelli,
M. Synlett 2002, 1807. (g) Berthiol, F.; Doucet, H.; Santelli,
M. Eur. J. Org. Chem. 2003, 1091.
(10) As a typical experiment, the reaction of 4-cyanobenzyl
bromide (1.00 g, 5.1 mmol), 4-methoxyphenylboronic acid
(1.55 g, 10.2 mmol) and K2CO3 (1.4 g, 10.2 mmol) at 130 °C
during 20 h in anhydrous xylene (10 mL) in the presence of
cis,cis,cis-1,2,3,4-tetrakis(diphenylphosphinomethyl)
cyclopentane–[PdCl(C3H5)]2 complex (0.0051 mmol) under
argon affords the corresponding adduct after extraction with
ether, evaporation and filtration on silica gel (dichloro-
methane) in 81% (0.92 g) isolated yield. 4-(4-Methoxy-
phenylmethyl)benzonitrile: 1H NMR (300 MHz, CDCl3):
d = 7.59 (d, J = 8.3 Hz, 2 H, Ar), 7.29 (d, J = 8.3 Hz, 2 H,
Ar), 7.11 (d, J = 8.6 Hz, 2 H, Ar), 6.88 (d, J = 8.6 Hz, 2 H,
Ar), 4.00 (s, 2 H, CH2), 3.82 (s, 3 H, OMe).
(11) Analytical data of selected products: Table 1 (entry 11): d =
7.71 (s, 1 H, Ar), 7.62 (s, 2 H, Ar), 7.35–7.10 (m, 5 H, Ph),
4.09 (s, 2 H, CH2); Table 1 (entry 16): d = 7.30–7.00 (m, 5
H, Ph), 7.08 (m, 1 H, Ar), 6.80 (m, 2 H, Ar), 3.94 (s, 2 H,
CH2); C13H10F2 (204.2): calcd. C 76.46, H 4.94; found C
Synlett 2003, No. 11, 1668–1672 © Thieme Stuttgart · New York