Highly efficient and regioselective allylation with allylic alcohols catalyzed by [Mo3S4Pd(η3-allyl)] clusters

Article abstract of DOI:10.1021/ol100805c

(Figure presented) A highly efficient and regioselective allylation reaction of amines and active methylene compounds directly using allylic alcohols under mild conditions catalyzed by the novel cubane-type sulfido [(CpMo)₃(μ₃-S)₄Pd(η³-allyl)] [PF₆]₂ clusters has been developed. A variety of allylic alcohols and nucleophiles including amines and active methylene compounds are investigated, and in the case of allylic alcohols bearing substituents at either the α- or γ-position only linear products are obtained.

Full text of DOI:10.1021/ol100805c

ORGANIC
LETTERS
2010
Vol. 12, No. 12
2726-2729
Highly Efficient and Regioselective
Allylation with Allylic Alcohols
Catalyzed by [Mo3S4Pd(η3-allyl)] Clusters
Yinsong Tao, Bo Wang, Baomin Wang, Lihong Qu, and Jingping Qu*
State Key Laboratory of Fine Chemicals, School of Chemical Engineering, Dalian
UniVersity of Technology, Dalian 116012, People’s Republic of China
qujp@dlut.edu.cn
Received April 8, 2010
ABSTRACT
A highly efficient and regioselective allylation reaction of amines and active methylene compounds directly using allylic alcohols under mild
conditions catalyzed by the novel cubane-type sulfido [(Cp*Mo)3(µ3-S)4Pd(η3-allyl)][PF6]2 clusters has been developed. A variety of allylic
alcohols and nucleophiles including amines and active methylene compounds are investigated, and in the case of allylic alcohols bearing
substituents at either the r- or γ-position only linear products are obtained.
Palladium-catalyzed allylic alkylations are important C-C
and C-heteroatom bond formation reactions with many
applications in organic synthesis.1 Most frequently, allyl
acetates and carbonates have been used as electrophiles in
these reactions, while from an economical and environmental
point of view, the direct use of allylic alcohols is more
profitable for two reasons.2 One is that the reaction of allylic
alcohols forms water as a coproduct, whereas allylic halides
and esters afford corresponding salt wastes under basic
conditions. The other is that allylic acetates and carbonates
are derivatives of allylic alcohol, and using allylic alcohols
directly can avoid redundant synthetic steps. To cleave the
inert C-O bond of allylic alcohol, some Lewis acids were
used, such as As2O3,3 B2O3,4 BPh3,5 BEt3,6 SnCl2,7 CO2,8
Ti(OiPr)4,9 Nb(OEt)5,10 carboxylic acid,11 and so on. Due
to the weak leaving capability for the OH group, successful
application of allylic alcohols without any activating reagents
is less reported.12
Ozawa and co-workers reported (η3-allyl)palladium com-
plexes bearing diphosphinidenecyclobutene ligand (DPCB)
catalyzed allylation of aniline and active methylene
(3) Lu, X.; Lu, L.; Sun, J. J. Mol. Catal. 1987, 41, 245.
(4) Lu, X.; Jian, X.; Tao, X. J. Organomet. Chem. 1998, 344, 109.
(5) Stary, I.; Stara, I. G.; Kocovsky, P. Tetrahedron Lett. 1993, 34, 179.
(6) (a) Kimura, M.; Futanmata, M.; Shibata, K.; Tamaru, Y. Chem.
Commun. 2003, 234. (b) Kimura, M.; Futamata, M.; Mukai, R.; Tamaru,
Y. J. Am. Chem. Soc. 2005, 127, 4592.
(7) Masuyama, Y.; Kagawa, M.; Kurusu, Y. Chem. Lett. 1995, 24, 1121.
(8) Sakamoto, M.; Shimizu, I.; Yamamoto, A. Bull. Chem. Soc. Jpn.
1996, 69, 1065.
(1) For recent reviews, see: (a) Lu, Z.; Ma, S. Angew. Chem., Int. Ed.
2008, 47, 258, and references cited therein. (b) Tsuji, J. In Palladium
Reagents and Catalysts: New PerspectiVes for the 21st Century; John Wiley
& Sons, Ltd.: Chichester, U.K., 2004; Chapter 4, p 431. (c) Trost, B. M.;
Vranken, D. L. V. Chem. ReV. 1996, 96, 395. (d) Trost, B. M. Acc. Chem.
Res. 1996, 29, 355.
(9) (a) Satoh, T.; Ikeda, M.; Miura, M; Nomura, M. J. Org. Chem. 1997,
62, 4877. (b) Yang, S.; Hung, C. J. Org. Chem. 1999, 64, 5000. (c) Yang,
S.; Tsai, Y. Organometallics 2001, 20, 763.
(10) Yamashita, Y.; Gopalarathnam, A.; Hartwig, J. F. J. Am. Chem.
Soc. 2007, 129, 7508.
(2) For recent reviews on allylation reaction of allylic alcohols, see: (a)
Muzart, J. Eur. J. Org. Chem. 2007, 3077, and references cited therein. (b)
Tamaru, Y. Eur. J. Org. Chem. 2005, 2647.
(11) (a) Manabe, K.; Kobayashi, S. Org. Lett. 2003, 5, 3241. (b) Patil,
N. T.; Yamamoto, Y. Tetrahedron Lett. 2004, 45, 3101. (c) Gan, K.; Jhong,
C.; Yang, S. Tetrahedron 2008, 64, 1204.
10.1021/ol100805c  2010 American Chemical Society
Published on Web 05/14/2010

compounds.12b Le Floch’s group tested the performance of
a range of cationic palladium complexes bearing mono- or
bidentate phosphane ligands and found [(η3-allyl)PdL2][NTf2]
(L ) 1,2,5-triphenylphosphole, Tf ) SO2CF3) was the best
catalyst for allylation with allyl alcohol.12e Recently, self-
assembling palladium phosphane catalysts were applied in
the allylation of N-heterocycles with allylic alcohols.12g
Although cationic palladium complexes incorporating the
π-allyl ligand have high catalytic activity, in the allylic
alkylation reaction, the regioselectivity is decreased due to
the formation of both linear and branched products.12b,e,g
Owing to novel structures and unique catalytic activities,
metal-sulfur cubane-type clusters have drawn much atten-
tion.13 Very recently we reported14 a highly efficient and
regioselective allylation reaction of amines with allylic
alcohols under mild conditions catalyzed by [(Cp*Mo)3(µ3-
S)4Pd(dba)][PF6]15 (Cp* ) η5-C5Me5; dba ) dibenzylide-
neacetone) with H3BO3 as an additive, and only linear
products were obtained by this catalytic system. Herein, our
extended study found that novel cubane-type sulfido clusters
[Mo3S4Pd(η3-allyl)] with η3-allyl ligands showed highly
efficient catalytic activity for the allylation reaction with
allylic alcohols without any additives under mild conditions.
Complexes [(Cp*Mo)3(µ3-S)4Pd(η3-C3H4R)][PF6]2 (1a, R
) H; 1b, R ) Ph) were synthesized by treating [(Cp*Mo)3(µ3-
S)4Pd(dba)][PF6] (2) with corresponding allylic halides and
AgPF6 in CH2Cl2 from 0 °C to room temperature and isolated
as yellowish green solids in 90 and 71% yields, respectively
(eq 1). Figure 1 shows the molecular structure of 1a. The
(Cp*Mo)3S4 chelates the (η3-allyl)palladium moiety through
three sulfur atoms. The bond length of Pd-C31 is similar
to Pd-C33. C31-C32 and C32-C33 bond lengths (1.389(16)
and 1.401(15) Å) and the C31-C32-C33 angle (115.8(11) °)
are in the typical ranges for η3-allyl ligands.
Neither the incomplete cubane-type cluster15 (entry 5) nor
the cubane-type sulfido cluster [Mo3PdS4] bearing dba or
PPh3 ligand15 (entries 6-7) could catalyze this reaction.
Figure 1. ORTEP representation of the molecular structure of 1a
with 30% probability ellipsoids. Hydrogen atoms and the PF6- ion
are omitted for clarity. Selected bond distances (Å) and angles (deg):
Pd-C31 2.124(11), Pd-C32 2.102(9), Pd-C33 2.183(10), C31-C32
1.389(16),C32-C331.401(15);C32-C31-Pd70.0(6),C33-C32-Pd
74.1(6), C31-C32-C33 115.8(11).
To our delight, we found 1a could smoothly catalyze
allylation of N-methylaniline by directly using allyl alcohol
without any additives and 96% yield was obtained in 24 h
The allylation of N-methylaniline (4a) with allyl alcohol
(3a) was chosen as a model reaction to study the catalytic
activity of 1 and other Pd complexes (eq 2). The results are
summarized in Table 1. In the presence of 5 mol % catalyst,
general Pd complexes (entries 1-4) have no or low activity
for this allylation reaction in CH2Cl2 under reflux conditions.
Table 1. Catalytic Activity of Pd Complexes and Cubane-Type
Sulfido Clustersa
(12) For Pd-catalyzed direct allylation reactions of allylic alcohols, see:
(a) Qu, J.; Ishimura, Y.; Nagato, N. Nippon Kagaku Kaishi 1996, 787. (b)
Ozawa, F.; Okamoto, H.; Kawagishi, S.; Yamamoto, S.; Minami, T.;
Yoshifuji, M. J. Am. Chem. Soc. 2002, 124, 10968. (c) Liang, H.; Ito, S.;
Yoshifuji, M. Org. Lett. 2004, 6, 425. (d) Kayaki, Y.; Koda, T.; Ikariya, T.
J. Org. Chem. 2004, 69, 2595. (e) Thoumazet, C.; Grutzmacher, H.;
Deschamps, B.; Ricard, L.; Le Floch, P. Eur. J. Inorg. Chem. 2006, 3911.
(f) Mora, G.; Deschamps, B.; van Zutphen, S.; Le Goff, X. F.; Richard, L.;
Le Floch, P. Organometallics 2007, 26, 1846. (g) Usui, I.; Schmidt, S.;
Keller, M.; Breit, B. Org. Lett. 2008, 10, 1207.
entry
cat.
yieldb (%)
1
2
3
4
5
6
7
8
9
PdCl2
0
0
0
32
0
0
0
PdCl2(PPh3)2
Pd(dba)2
Pd(PPh3)4
(13) For recent reviews, see: (a) Hidai, M.; Kuwata, S. Acc. Chem. Res.
2000, 33, 46. (b) Hernandez-Molina, R.; Sokolov, M. N.; Sykes, A. G.
Acc. Chem. Res. 2001, 34, 223. For catalytic activity of metal-sulfur
cubane-type clusters, see: (c) Murata, T.; Mizobe, Y.; Gao, H.; Ishii, Y.;
Wakabayashi, T.; Nakano, F.; Tanase, T.; Yano, S.; Hidai, M.; Echizen, I.;
Nanikawa, H.; Motomura, S. J. Am. Chem. Soc. 1994, 116, 3389. (d)
Wakabayashi, T.; Ishii, Y.; Ishikawa, K.; Hidai, M. Angew. Chem., Int.
Ed. 1996, 35, 2123. (e) Takei, I.; Wakebe, Y.; Suzuki, K.; Enta, Y.; Suzuki,
T.; Mizobe, Y.; Hidai, M. Organometallics 2003, 22, 4639. (f) Takei, I.;
Enta, Y.; Wakebe, Y.; Suzuki, T.; Hidai, M. Chem. Lett. 2006, 35, 590. (g)
Feliz, M.; Guillamon, E.; Llusar, R.; Vicent, C.; Stiriba, S.; Perez-Prieto,
J.; Barberis, M. Chem.sEur. J. 2006, 12, 1486.
[(Cp*Mo)3(µ2-S)3(µ3-S)][PF6]
[(Cp*Mo)3(µ3-S)4Pd(dba)[PF6] (2)
[(Cp*Mo)3(µ3-S)4Pd(PPh3)][PF6]
[(Cp*Mo)3(µ3-S)4Pd(η3-C3H5)][PF6]2 (1a)
96 (94)c
90
[(Cp*Mo)3(µ3-S)4Pd(η3-C3H4Ph)][PF6]2 (1b)
a Reaction conditions: cat. 0.02 mmol, N-methylaniline 0.4 mmol, allyl
alcohol 0.4 mmol, CH2Cl2 1 mL, reflux, 24 h. b Determined by GC with
naphthalene as an internal standard. c Isolated yield.
(14) Tao, Y.; Zhou, Y.; Qu, J.; Hidai, M. Tetrahedron Lett. 2010, 51,
1982.
Org. Lett., Vol. 12, No. 12, 2010
2727

(entry 8). Compound 1b exhibited comparable catalytic
activity with 1a (entry 9) and gave 90% yield of product.
and the mole ratio was 71:29. Other para-substituted aniline
derivatives with Cl and NO2 groups underwent the allylation
reaction smoothly to afford corresponding mono- and dial-
lylation products, respectively. The ratio of products is similar
to 4d (entries 4 and 5).
Table 2. Allylation of Amines with Allylic Alcohols Catalyzed
by 1aa
Table 3. Allylation of Active Methylene Compounds with
Allylic Alcohols Catalyzed by 1aa
a Reaction conditions: 1a 0.02 mmol, amine 0.4 mmol, allylic alcohol
0.4 mmol, CH2Cl2 1 mL, reflux, 24 h. b Isolated yield. c Yield based on
anilines. d E/Z ) 5.8:1. e E/Z ) 5.1:1.
a Reaction conditions: 1a 0.02 mmol, active methylene compound
0.4 mmol, allylic alcohol 0.4 mmol, CH2Cl2 1 mL, reflux, 24 h. b Isolated
yield.
We chose 1a as the catalyst and investigated the reactions
of a series of amines and allylic alcohols for activity and
regioselectivity (Table 2). Besides 4a, the other secondary
amine, 4b, was also examined and good yield was obtained
(entry 1). Acetanilide (4c), which has lower nucleophilicity
than 4a, also gave good yield (entry 2). For the primary
amines, when equivalence of aniline and allyl alcohol were
applied, both mono- and diallylation products were obtained
The reactions of allylic alcohols bearing a methyl or phenyl
substituent at either the R- or γ- position were examined.
Both crotyl alcohol and 3-butene-2-ol (entries 6 and 7)
reacted with 4a to produce 5g without any detection of
branched products. Cinnamyl alcohol and R-vinylbenzyl
alcohol as substrates also gave good yield and only the E
product 5h. These results apparently indicated that this
reaction proceeded via a common π-allylpalladium interme-
diate.
(15) Takei, I.; Suzuki, K.; Enta, Y.; Dohki, K.; Suzuki, T.; Mizobe, Y.;
Hidai, M. Organometallics 2003, 22, 1790.
2728
Org. Lett., Vol. 12, No. 12, 2010

produts of 5g, the reaction of 3b and 3c with 6c gave only
7h with E configuration.
Scheme 1. Proposed Mechanism for Allylation Reaction
The proposed mechanism of this catalytic reaction was
shown in Scheme 1. Proton produced by nucleophilic attack
of nucleophile to 1 promoted the C-O bond cleavage of
allylic alcohol. This process is analogous to Pd- or Ru-
catalyzed allylation reaction reported by Le Floch16 and
Pregosin’s17 group, respectively. The regeoselectivity is
ascribed to the nucleophilic attack of nucleophile to the less
hindered allyl carbon in A (Scheme 1).
In summary, under mild conditions, a highly efficient and
regioselective allylation reaction of amines and active
methylene compounds directly using allylic alcohols cata-
lyzed by novel [(Cp*Mo)3(µ3-S)4Pd(η3-C3H4R)][PF6]2 (R )
H, Ph) complexes has been described. A variety of allylic
alcohols and nucleophiles were investigated. The reaction
proceeded with excellent regioselectivity, leading to a linear
product for allylic alchols bearing substituents at either the
R- or γ-position.
Acknowledgment. This work was supported by the
National Natural Science Foundation of China (No. 20806012)
and the Program for Changjiang Scholars and Innovative
Research Team in University (No. IRT0711).
Encouraged by this result, we further investigated the
allylation reaction of active methylene compounds with
allylic alcohol (Table 3). 2-Nitro-1-phenylethanone (6a) as
nucleophile could smoothly react with 3a to produce
monoallylation product 7a in 83% yield. 3-Benzoyl-dihydro-
furan-2-one (6b) reacted with allyl alcohol affording moder-
ate yield. In this catalytic system, 2-carboxylsubstituted-1-
indanone or 1-tetralone compounds also reacted with allyl
alcohol to give corresponding products in high yield (entries
3-7). Substituents in phenyl did not affect the catalytic
activity. To our surprise, different from the mixture Z and E
Supporting Information Available: Experimental pro-
cedures and characterization of all new compounds. This
material is available free of charge via the Internet at
http://pubs.acs.org.
OL100805C
(16) Piechaczyk, O.; Thoumazet, C.; Jean, Y.; Le Floch, P. J. Am. Chem.
Soc. 2006, 128, 14306.
(17) Zaitsev, A. B.; Gruber, S.; Pregosin, P. S. Chem. Commun. 2007,
4692.
Org. Lett., Vol. 12, No. 12, 2010
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