Palladium-catalyzed formal [4+2] cycloaddtion of o-xylylenes with olefins

Article abstract of DOI:10.1021/ja070012l

o-(Silylmethyl)benzylic carbonates reacted with various conjugated olefins in the presence of the palladium catalyst, which was generated in situ from Pd(η³-C₃H₅)Cp and 1,2-bis(diphenylphosphino)ethane (DPPE). The reaction

Full text of DOI:10.1021/ja070012l

Published on Web 03/13/2007
Palladium-Catalyzed Formal [4+2] Cycloaddtion of o-Xylylenes with Olefins
Ryoichi Kuwano* and Takenori Shige
Department of Chemistry, Graduate School of Sciences, Kyushu UniVersity, 6-10-1 Hakozaki,
Higashi-ku, Fukuoka 812-8581, Japan
Received January 2, 2007; E-mail: rkuwascc@mbox.nc.kyushu-u.ac.jp
Scheme 1
Diels-Alder reaction, that is, [4+2] cycloaddition of 1,3-dienes
with alkenes, is an attractive method to construct 6-membered
carbocycles.1 The reaction generally requires high temperature to
obtain the desired cycloadduct in high yield.2 The cycloaddition is
known to accelerate in the presence of varied metal complexes.3
The metal-mediated methodology has contributed to the advance
of stereoselective cycloaddition.4 Meanwhile, o-xylylenes, which
are 1,3-cyclohexadienes having two exomethylenes at the 5- and
6-positions, have a remarkable reactivity for Diels-Alder reaction
as a diene.5 Various methods for in-situ generation of o-xylylene
Table 1. Effect of Solvent and Ligand on Cycloaddition of 1a with
have been developed6 and utilized for the syntheses of natural
products.7 However, it is hard to control the intermolecular reaction
of o-xylylene because of its violent reactivity.8 This paper describes
a new organometallic methodology for generating an o-xylylene
equivalent, which reacted with various conjugated olefins to yield
the [4+2] cycloadduct.
2aa
We have developed the palladium-catalyzed nucleophilic sub-
stitutions of benzylic carbonates recently.9 The catalytic reaction
proceeds through the benzylic C-O bond activation by palladium-
(0). As shown in Scheme 1, we envisioned that the o-xylylene
equivalent A or B would be generated from o-(metalated-methyl)-
benzyl carbonate 16f,10 through the C-O bond cleavage leading to
(benzyl)palladium C. The M and palladium(II) of C would undergo
intramolecular transmetalation leading to 2-palladaindane A (path
a),11 which might give the tetralin cycloadduct through olefin
insertion followed by reductive elimination. Alternatively, the
benzylic carbon bound to M would behave as a carbanion (path
b). The carbanion of B might undergo 1,4-addition to an R,â-
unsaturated carbonyl compound, and then the resulting enolate
might attack the η3-benzyl on palladium(II). The above hypothesis
stimulated us to attempt the reaction of o-[(trimethylsilyl)methyl]-
benzyl carbonate 1a with methyl acrylate 2a in the presence of a
palladium(0) complex.
entry
solvent
ligand
yield (%)b
1c
2
3
4
5
6
7
8
9
DMSO
DMSO
DMF
DPPE
DPPE
DPPE
DPPE
DPPE
DPPE
DPPF
DPEphos
2 PPh3
78d
60
72
45
7
MeCN
1,4-dioxane
toluene
DMSO
DMSO
DMSO
5
32
30
10
a Reactions were conducted in 1 mL of solvent. The ratio of 1a (0.15
mmol)/2a/[Pd]/ligand was 100:120:3:3.3. b GC yield (average of two runs).
c The reaction was conducted by using 0.5 mmol of 1a in 1 mL DMSO for
48 h. d Isolated yield.
A mixture of 1a and 2a in DMSO was heated at 120 °C for 48
h in the presence of 3% palladium catalyst prepared from Pd(η3-
C3H5)Cp and a bidentate ligand DPPE12 (Table 1, entry 1). Tetralin-
2-carboxylate 3a, which is the cycloadduct of o-xylylene with 2a,
was obtained in 78% isolated yield. The use of a Lewis basic solvent
is crucial for the catalytic reaction. The desired product 3a was
obtained in reasonable yield when the reaction was conducted in
DMF as well as in DMSO (entry 2). In contrast, 1a was hardly
consumed in 1,4-dioxane or toluene (entries 5, 6). The yield of 3a
was significantly affected by the ligand on palladium. The use of
bisphosphine DPPF and DPEphos, which were effective for the
palladium-catalyzed nucleophilic substitution of benzylic esters,9,13
slowed the production of 3a (entries 7, 8). The monophosphine-
ligated palladium did not work as a catalyst for the cycloaddition
very well (entry 9). No 3a was obtained from the reaction of 1a
and 2a with DPPE in the absence of palladium.
amount of [2,2]orthocyclophane 4 (<3%), which might have formed
through Hiyama cross-coupling of two 1a (eq 1).14 No formation
of o-xylylene dimer 5 was detected in the resulting mixture by GC
and 1H NMR analysis.15 This observation may rule out the reaction
pathway involved with palladium-mediated generation of free
o-xylylene and its pericyclic cycloaddition with the dienophile. The
cycloaddition of 1a with 2a occurred on the DPPE-ligated palladium
atom and proceeds through either reactive intermediate A or B.13
Various conjugated olefins 2 underwent the catalytic formal
[4+2] o-xylylene cycloaddition (Table 2). The o-xylylene precursor
1a reacted with acrylates substituted at the trans or geminal position,
The mixture of 1a and DPPE-palladium catalyst in DMSO was
heated to 120 °C for 24 h in the absence of 2a, affording a trace
9
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J. AM. CHEM. SOC. 2007, 129, 3802-3803
10.1021/ja070012l CCC: $37.00 © 2007 American Chemical Society

C O M M U N I C A T I O N S
Table 2. Palladium-Catalyzed Cycloaddition of 1a with Olefins (2)a
the reaction was conducted in Lewis basic solvent, as well as by
using a DPPE-palladium catalyst. The present catalytic reaction
is equivalent to the [4+2] o-xylylene cycloaddition with dienophiles.
Use of a chiral ligand in place of DPPE may lead to a catalytic
asymmetric cycloaddition of o-xylylenes with olefins.
Acknowledgment. This work was supported by Grant-in-Aids
(No. 16685011 and 18655019) from MEXT. This paper is dedicated
to the memory of Professor Yoshihiko Ito.
Supporting Information Available: Experimental procedures and
characterization data for all new compounds. This material is available
free of charge via the Internet at http://pubs.acs.org.
References
(1) Reviews: (a) Nicolaou, K. C.; Snyder, S. A.; Montagnon, T.; Vassiliko-
giannakis, G. Angew. Chem., Int. Ed. 2002, 41, 1668-1698. (b) Stocking,
E. M.; Williams, R. M. Angew. Chem., Int. Ed. 2003, 42, 3078-3115.
(c) Takao, K.-i.; Munakata, R.; Tadano, K.-i. Chem. ReV. 2005, 105,
4779-4807.
(2) Oppolzer, W. Intermolecular Diels-Alder Reactions. In ComprehensiVe
Organic Syntheis Vol. 5: Combining C-C π-Bond; Trost, B. M., Fleming,
I., Paquette, L. A., Eds.; Pergamon Press: Oxford, 1991; pp 315-399.
(3) (a) Jolly, R. S.; Luedtke, G.; Sheehan, D.; Livinghouse, T. J. Am. Chem.
Soc. 1990, 112, 4965-4966. Review: (b) Lautens, M.; Klute, W.; Tam,
W. Chem. ReV. 1996, 96, 49-92.
(4) (a) McKinstry, L.; Livinghouse, T. Tetrahedron 1994, 50, 6145-6154.
(b) Gilbertson, S. R.; Hoge, G. S.; Genov, D. G. J. Org. Chem. 1998, 63,
10077-10088. (c) Heath, H.; Wolfe, B.; Livinghouse, T.; Bae, S. K.
Synthesis 2001, 2341-2347. Review of asymmetric Diels-Alder reaction
using Lewis acid catalyst: (d) Corey, E. J. Angew. Chem., Int. Ed. 2002,
41, 1650-1667.
(5) Reviews: (a) Charlton, J. L.; Alauddin, M. M. Tetrahedron 1987, 43,
2873-2889. (b) Segura, J. L.; Martin, N. Chem. ReV. 1999, 99, 3199-
3246.
a The detail of reaction conditions was given in Supporting Information.
b Isolated yield. c A small amount of cis-3e (trans/cis ) 93:7) was detected
in 1H NMR analysis of the crude product. d Isolated yield of pure trans-3e.
e The reaction was conducted at 140 °C.
Table 3. Palladium-Catalyzed Cyclization of 1b-e with 2aa
(6) Selected examples of in-situ generation of o-xylylenes: (a) Oppolzer, W.
J. Am. Chem. Soc. 1971, 93, 3833-3834. (b) Ito, Y.; Nakatsuka, M.;
Saegusa, T. J. Am. Chem. Soc. 1982, 104, 7609-7622. (c) Askari, S.;
Lee, S.; Perkins, R. R.; Scheffer, J. R. Can. J. Chem. 1985, 63, 3526-
3529. (d) Sano, H.; Ohtsuka, H.; Migita, T. J. Am. Chem. Soc. 1988, 110,
2014-2015. (e) Lenihan, B. D.; Shechter, H. J. Org. Chem. 1998, 63,
2072-2085. (f) Fleming, I.; Morgan, I. T.; Sarkar, A. K. J. Chem. Soc.
Perkin Trans. 1 1998, 2749-2746. (g) Kakiya, H.; Shinokubo, H.; Oshima,
K. Bull. Chem. Soc. Jpn. 2000, 73, 2139-2147. (h) Kuwano, R.; Shige,
T. Chem. Lett. 2005, 34, 728-729.
entry
R (1)
product (3)
ratiob
yield (%)c
(7) (a) Nicolaou, K. C.; Gray, D. L. F. J. Am. Chem. Soc. 2004, 126, 607-
612. (b) Matsuya, Y.; Sasaki, K.; Nagaoka, M.; Kakuda, H.; Toyooka,
N.; Imanishi, N.; Ochiai, H.; Nemoto, H. J. Org. Chem. 2004, 69, 7989-
7993.
1
2
3
4
4-MeO (1b)
4-Me (1c)
3-Ph (1d)
3h, 3h′
3i, 3i′
3j, 3j′
3k, 3k′
60:40
54:46
55:45
60:40
42
72
92
51
4,6-Me2 (1e)
(8) Bach achieved a highly enantioselective cycloaddition of an o-xylylene
by using an excess of a chiral template. (a) Grosch, B.; Orlebar, C. N.;
Herdtweck, E.; Massa, W.; Bach, T. Angew. Chem., Int. Ed. 2003, 42,
3693-3696. (b) Grosch, B.; Orlebar, C. N.; Herdtweck, E.; Kaneda, M.;
Wada, T.; Inoue, Y.; Bach, T. Chem.sEur. J. 2004, 10, 2179-2189.
(9) (a) Kuwano, R.; Kondo, Y.; Matsuyama, Y. J. Am. Chem. Soc. 2003,
125, 12104-12105. (b) Kuwano, R.; Kondo, Y. Org. Lett. 2004, 6, 3545-
3547. (c) Kuwano, R.; Kondo, Y.; Shirahama, T. Org. Lett. 2005, 7, 2973-
2975.
(10) Yoshida and Kunai used 1 (M ) Si) for the palladium-catalyzed
distannylation of o-xylylene. They conducted the reaction in the presence
of KF in order to generate a free o-xylylene from 1. The free o-xylylene
reacted with hexabutylditin activated by palladium(0). Yoshida, H.;
Nakano, S.; Yamaryo, Y.; Ohshita, J.; Kunai, A. Org. Lett. 2006, 8, 4157-
4159.
a The detail of reaction conditions was given in Supporting Information.
b The ratio was determined with 1H NMR analysis. It is uncertain which is
the major product, 3 or 3′. c Yield of a mixture of 3 and 3′.
yielding the corresponding tetralin products (entries 1-3). No
formation of cis-2,3-disubstituted tetralins was detected in the
catalytic cycloadditions of trans-dienophiles 2b and 2c.16 Olefins
conjugated with ketone, nitrile, and benzene worked as a dienophile
(entries 4-6). However, the palladium catalysis failed to react 1a
with strongly electron-deficient olefins, such as maleate and
fumarate,17 as well as cyclic ones.
As shown in Table 3, the DPPE-palladium complex was
effective for the reaction of compounds 1b-e bearing substituents
on the aromatic ring.18 For example, 3-phenyl-substituted 1d reacted
with 2a to give the desired tetralins in 92% yield (entry 3). The
substituent at the 6-position of 1e barely hindered the catalytic
cycloaddition (entry 4). In all cases, cycloaddition products were
obtained as a regioisomeric mixture of 3h-k and 3h′-k′ (54:46-
60:40).19 The low regioselectivity indicates that the cycloaddition
of 1 proceeds through intermediate A in Scheme 1. If the reaction
was involved with path b, tetralin 3h-k would be obtained with
perfect regioselectivity.
(11) Tanaka reported an enantioselective rhodium-catalyzed [4+2] carbocy-
clization of 2-alkynylbenzaldehydes. The authors proposed 2-metallaindane
intermediate for the cataytic reaction. Tanaka, K.; Hagiwara, Y.; Noguchi,
K. Angew. Chem., Int. Ed. 2005, 44, 7260-7263.
(12) DPPE ) 1,2-bis(diphenylphosphino)ethane.
(13) Although DPPE was inefficient for the catalytic substitution of benzylic
carbonates in our previous report (ref 9a), DPPE-[Pd(η3-C3H5)(cod)]BF4
catalyst could activate the benzylic C-O bond and catalyze the reaction
of methyl o-methylbenzyl carbonate with dibutylamine in DMSO at 120
°C, giving the benzylated tertiary amine in 42% yield.
(14) Hatanaka, Y.; Hiyama, T. J. Org. Chem. 1988, 53, 918-920.
(15) Errede, L. A. J. Am. Chem. Soc. 1961, 83, 949-954.
(16) â-cis-Methylstyrene reacted with 1a to afford the cis-cycloadduct ste-
reospecifically. However, yield of the product was low (14%).
(17) The electron-deficient olefins may bind tightly to palladium(0) to obstruct
the interaction of 1a and catalyst.
(18) No cycloadduct was obtained from the reaction of the substrate 1 having
a methyl on its R-position of the carbonate group.
(19) Each reaction of 1c and 1d gave the same major regioisomers to the
fluoride-induced o-xylylene [4+2] cycloaddtion in ref 6h (1c, major/minor
) 52:48; 1d, major/minor ) 55:45).
In conclusion, we developed the palladium-catalyzed [4+2]
cycloaddition of o-(silylmethyl)benzylic carbonates with olefins.
The desired tetralin products were obtained with good yield when
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