Catalytic amphiphilic allylation via bis-π-allylpalladium complexes and its application to the synthesis of medium-sized carbocycles

Article abstract of DOI:10.1021/ja002931g

The reaction of certain activated alkenes 3 with allyltributylstannane (4) and allyl chloride (5a) in the presence of palladium catalyst gave the bis-allylation products, 1,7-octadiene derivatives 6a-k, in good to high yields. The reaction of certain imin

Full text of DOI:10.1021/ja002931g

372
J. Am. Chem. Soc. 2001, 123, 372-377
Catalytic Amphiphilic Allylation via Bis-π-allylpalladium Complexes
and Its Application to the Synthesis of Medium-Sized Carbocycles
Hiroyuki Nakamura, Kouichi Aoyagi, Jae-Goo Shim, and Yoshinori Yamamoto*
Contribution from the Department of Chemistry, Graduate School of Science, Tohoku UniVersity,
Sendai 980-8578, Japan
ReceiVed August 7, 2000
Abstract: The reaction of certain activated alkenes 3 with allyltributylstannane (4) and allyl chloride (5a) in
the presence of palladium catalyst gave the bis-allylation products, 1,7-octadiene derivatives 6a-k, in good to
high yields. The reaction of certain imines 9 with 4 and 5a under similar conditions as above afforded the
bis-allylated amines, N-allyl-N-3-butene-1-amine derivatives 10a-f, in good to high yields. The bis-allylation
reactions most probably proceed through bis-π-allylpalladium intermediate 2. The above intermolecular bis-
allylation was extended to the intramolecular reaction. The reaction of 8-chloro-2,6-octadienyltributylstannane
(17a) with activated alkenes 3 gave a mixture of regioisomeric cycloadducts, [8+2] and [4+2] cycloaddition
products. The regioisomeric ratio was dependent on solvent and the electron density at the â-position of activated
alkenes. In general, the [8+2] cycloadducts 18 were obtained predominantly in CH2Cl2, whereas the [4+2]
adducts 24 and 25 were produced predominantly in DMF. The reaction of 7-chloro-2,8-nonadienyltributyl-
stannane (17b) with activated alkenes gave selectively the [9+2] cycloadducts 19 and 22: the regioisomeric
[5+2] and [7+2] adducts were not obtained at all. The reaction of 10-chloro-2,8-decadienyltributylstannane
(17c) with activated alkene 3a afforded the [10+2] cycloadducts 20 and 23 in low yields. The mechanism on
the intramolecular bis-allylation reaction is discussed.
Introduction
Scheme 1
Palladium-catalyzed allylation with various nucleophiles
(Tsuji-Trost-type reaction) is now a very important modern
organic transformation for the construction of carbon-carbon
or carbon-heteroatom bonds.1 It is widely accepted that
π-allylpalladium complexes 1,
Scheme 2
which are key intermediates for the Tsuji-Trost reaction, have
an electrophilic character and react with nucleophiles to afford
the corresponding allylation products. Recently, we found that
bis-π-allylpalladium complex 2 reacts with electrophiles such
as aldehydes and imines to produce the carbon-carbon bond
in a manner different from the reaction via 1.2-4 In this reaction,
one of the two allyl groups of the bis-π-allylpalladium complex
reacted with electrophiles and the other stayed on the palladium
atom. Furthermore, we communicated that, in the reaction with
certain R,â-unsaturated carbonyl compounds, bis-π-allylpalla-
dium complex 2 acts as the first amphiphilic catalytic allylating
agent (Scheme 1).5 It occurred to us that bis-π-allylpalladium
complexes, in which two π-allyl units are bonded through a
carbon tether, may react with certain Michael acceptors in an
amphiphilic manner (Scheme 2) to produce the corresponding
carbocycles. We now report the full account for the previous
(3) Although π-allylpalladium-X complexes 1 in which X is an electron-
withdrawing group react with nucleophiles, it is also known that certain
π-allyl transition metal complexes react with electrophiles. π-Allylmolyb-
denum complexes: (a) Faller, J. W.; Nguyen J. T.; Ellis, W.; Mazzieri, M.
R. Organometallics 1993, 12, 1434. (b) Faller, J. W.; DiVerdi, M. J.; John,
J. A. Tetrahedron Lett. 1991, 32, 1271. (c) Faller, J. W.; Linebarrier, D. L.
J. Am. Chem. Soc. 1989, 111, 1937. π-Allylnickel complexes: (d) Hegedus,
L. S.; Wagner, S. D.; Waterman, E. L.; Siirala-Hansen, K. J. Org. Chem.
1975, 40, 593. π-Allyltitanium complexes: (e) Sato, F.; Iijima, S.; Sato,
M. Tetrahedron Lett. 1981, 22, 243. (f) Collins, S.; Kuntz, B. A.; Hong, Y.
J. Org. Chem. 1989, 54, 4154. For recent papers on the oxidative addition
of allylic halides to Pd(0) see: (g) Kurosawa, H.; Kajimaru, H.; Ogoshi,
S.; Yoneda, H.; Miki, K.; Kasai, N.; Murai, S.; Ikeda, I. J. Am. Chem. Soc.
1992, 114, 8417. Kurosawa, H.; Ogosi, S. Bull. Chem. Soc. Jpn. 1998, 71,
973. For the (η1-allyl)(η3-allyl)palladium complex see: (h) Kuhn, O.; Mayr,
H. Angew. Chem., Int. Ed. 1999, 38, 343.
(1) (a) Tsuji, J. In Palladium Reagents and Catalysts; John Wiley and
Sons: Chichester, 1995; p 61. (b) Codleski, S. A. In ComprehensiVe Organic
Synthesis; Semmelhack, M. F., Ed.; Pergamon Press: Oxford, 1991; Vol.
4, p 585. (c) Collman, J. P.; Hegedus, L. S.; Norton, J. R.; Finke, R. G. In
Principles and Applications of Organotransition Metal Chemistry; Univer-
sity Science Books: Mill Valley, 1987; p 417.
(2) (a) Nakamura, H.; Iwama, H.; Yamamoto, Y. J. Chem. Soc., Chem.
Commun. 1996, 1459. (b) Nakamura, H.; Iwama, H.; Yamamoto, Y. J. Am.
Chem. Soc. 1996, 118, 6641 and references therein.
(4) (a) Nakamura, H.; Nakamura, K.; Yamamoto, Y. J. Am. Chem. Soc.
1998, 120, 4242. (b) Nakamura, K.; Nakamura, H.; Yamamoto, Y. J. Org.
Chem. 1999, 64, 2614. (c) Bao, M.; Nakamura, H.; Yamamoto, Y.
Tetrahedron Lett. 2000, 41, 131.
(5) Nakamura, H.; Shim, J.-G.; Yamamoto, Y. J. Am. Chem. Soc. 1997,
119, 8113.
10.1021/ja002931g CCC: $20.00 © 2001 American Chemical Society
Published on Web 12/22/2000

Synthesis of Medium-Sized Carbocycles
J. Am. Chem. Soc., Vol. 123, No. 3, 2001 373
Table 1. Palladium-Catalyzed Bis-Allylation of the Imines 9a-f
and p-Toluenesulfonyl Isocyanate 9g with Allyltributylstannane (4)
and Allyl Chloride (5a)a
results on the intermolecular amphiphilic bis-allylation reactions
(Scheme 1) together with new findings on the intramolecular
version of the bis-allylation (Scheme 2).
entry
9
solvent
products
yield (%)b
Results and Discussion
1
2
3
4
5
6
7c
9a
9b
9c
9d
9e
9f
DMF
DMF
DMF
DMF
DMF
DMF
THF
10a
10b
10c
10d + 11d
10e + 11e
11f
81
74
53
Intermolecular Amphiphilic Bis-Allylation Reaction. The
reaction of phenylethylidene malononitrile (3a, 1 equiv), allyl-
tributylstannane (4, 1.2 equiv), and allyl chloride (5a, 1.2 equiv)
in THF was carried out in the presence of PdCl2(PPh3)2 (3 mol
%) under Ar atmosphere at room temperature (eq 1), giving
84 (46/54)
78 (44/56)
98
9g
10g
86
a The reactions were carried out in the presence of Pd2dba3‚CHCl3
catalyst (5 mol %) in DMF at room temperature. b Isolated yields based
on 9. The product ratios of 10 and 11 are indicated in parentheses.
c Tricyclohexylphosphine (20 mol %) was used as a ligand in the
reaction.
the diastereoselectivities of the reactions were not high. Even
the olefin 3k activated by a single CN group gave the
amphiphilic allylation product 6k in an allowable yield.
Not only the C-C activated unsaturated compounds 3, but
also certain activated C-N unsaturated compounds, such as the
imines 9a-f and isocyanate 9g, underwent the amphiphilic bis-
allylation reaction (eq 2). The results are shown in Table 1.
4,4-dicyano-5-phenyl-1,7-octadiene (6a) in 99%. The use of 5
mol % and 1.5 mol % of the catalyst also gave 6a in 99% and
98% yields, respectively. Allyl bromide (5b), iodide (5c), acetate
(5d), and alcohol (5e) were less effective compared to allyl
chloride (5a). The solvent effect was also examined: acetonitrile
and N,N-dimethylformamide (DMF) as well as THF were
effective, nitromethane was less effective, and nonpolar solvents
such as toluene and CH2Cl2 were not effective. Tetrakis-
(triphenylphosphine)palladium as well as dichlorobis(tri-
phenylphosphine)palladium were efficient catalysts. The use of
tetrakis(triphenylphosphine)palladium catalyst gave 6a in 99%
yield under the same reaction conditions. In all cases the
monoallylated products 7 and 8 were not obtained. Other
palladium catalysts, such as Pd(dba)2, Pd(OAc)2, and PdCl2-
(PBu3)2, were not effective for this reaction and the use of Ni-
(PPh3)4 as a catalyst in THF gave the monoallylated product
7a (R1 ) Ph, E1 ) E2 ) CN) in 70% yield along with small
amounts (∼9%) of 6a.
The reaction of imine 9a, derived from 4-nitrobenzaldehyde and
methylamine, with allyltributylstannane (4) and allyl chloride
(5a) proceeded very smoothly in the presence of Pd2dba3‚CHCl3
catalyst in DMF at room temperature, giving N-allyl-N-methyl-
1-(4-nitrophenyl)-3-buten-1-amine (10a) in 81% yield (entry 1).
Imines 9b and 9c, derived from n-butylamine and benzylamine,
respectively, also underwent the amphiphilic bis-allylation to
afford 10b and 10c in good yields (entries 2 and 3). However,
the reactions of imines 9d and 9e, derived from aniline, gave
approximately 1:1 mixtures of the mono- (11d and 11e,
respectively) and bis-allylated products (10d and 10e, respec-
tively) in good to high yields (entries 4 and 5), whereas only
the mono-allylated product 11f was obtained in almost quantita-
tive yield in the case of imine 9f, derived from the electron-
deficient amine methyl 4-aminobenzoate (entry 6). Tosyl
isocyanate (9g) also underwent the amphiphilic bis-allylation
very smoothly to give N-tosyl-N-allyl-3-butenamide (10g) in
86% yield (entry 7).
Various activated olefins were examined and the results were
reported in the previous communication.5 The activated olefins
(3b-d) underwent the double allylation very smoothly to give
the corresponding 1,7-octadienes (6b-d) in high yields. Not
only the activated olefins having two CN groups (3a-d) but
also those bearing CN and CO2Et (3e-h) or CN and SO2Ph
(3i-j) underwent the double allylation reaction, giving the
corresponding octadienes (6e-j) in 43-80% yields, although

374 J. Am. Chem. Soc., Vol. 123, No. 3, 2001
Nakamura et al.
Scheme 3
reactions the bis-π-allylpalladium complex 14 is a key inter-
mediate and reacts with the carbon-heteroatom double bond
of 15 at the C3 and C6 positions regioselectively (exo-exo
cycloaddition mode) to afford the corresponding heterocyclic
products 16.16 If the bis-π-allylpalladium mechanism, which is
operative in the intermolecular palladium-catalyzed allyl stan-
nane-allyl chloride reaction (Scheme 3), is also operative for
17a, the intermediate 14 must be generated (eq 3). From 1,3-
butadiene, bis-π-allylpalladium (14) having only a tether of two
carbon chain is obtained. However, the intramolecular version
of the allylic stannane-allyl chloride reaction makes it feasible
to obtain bis-π-allylpalladiums bearing tethers of three and four
carbon chains (17b and 17c) as well as tethers of the two carbon
chain. The syntheses of 17a-c are shown in the Supporting
Information.
We first examined the reactions of 17a with isocyanates 9g
and 9h in the presence of Pd(PPh3)4 catalyst (10 mol %) in
THF at room temperature. It was expected that 17a would
produce 14 as a reactive intermediate, which would react with
9 at the C3 and C6 positions, as observed previously (see eq
3). Actually, the reaction proceeded in an exo-exo cyclization
mode to give the corresponding divinylpiperidones 16g and
16h15 in 50% and 44% yields, respectively (eq 4).
A mechanistic rationale which accounts for the unprecedented
amphiphilic bis-allylation of activated olefins 3 is shown in
Scheme 3. The transmetalation of allyltributylstannane to
palladium would produce bis-π-allylpalladium complex 2,6
which would react with activated olefins 3 to give the π-al-
lylpalladium intermediate 12. The reductive coupling from 12
would give the corresponding 1,7-octadienes 6 and palladium-
(0) species. At this stage, the π-allyl group of 12 reacts with a
nucleophilic carbon center. The oxidative insertion of Pd(0) into
allyl chloride would produce the π-allylpalladium chloride
complex 13. When Pd(PPh3)4 was used as a catalyst instead of
PdCl2(PPh3)2, the catalytic cycle would start from the Pd(0)
species. The reaction of 13 with allyltributylstannane would
produce 2 and Bu3SnCl.
[n+2] Cycloaddition via the Intramolecular Amphiphilic
Bis-Allylation Reaction. Several useful transition metal-
catalyzed synthetic methods for medium-sized rings have been
developed recently: for example, the ring-closing metathesis,7
the ring-expansion reactions,8 and the intramolecular cycliza-
tions.9 However, to the best of our knowledge, very few
examples for the [n+m] cycloaddition method are known.10
Accordingly, we extended the intermoleculer amphiphilic bis-
allylation reaction to the intramolecular bis-π-allylpalladium
system (Scheme 2). Palladium-catalyzed reactions of 1,3-
butadiene with carbon-heteroatom unsaturated compounds 15,
such as aldehydes,11-13 ketones,13b imines,14 and isocyanates,15
are well-known as a novel method for the synthesis of the six-
membered heterocycles (eq 3). It is thought that in these
Next, we examined the reactions of 17a with the activated
olefins 3 (eq 5). The results are summarized in Table 2. The
reaction of 17a with 3a proceeded smoothly in the presence of
Pd(PPh3)4 catalyst (10 mol %) in THF at room temperature to
give, as expected, the corresponding [4+2] cycloaddition (exo-
exo mode) products 24a and 25a in 19% and 10% yields,
respectively (entry 1). Very interestingly, a trace amount of the
[8+2] cycloaddition (endo-endo mode) product 18a (n ) 1)
was also obtained (entry 1). The combined yield of the products
increased up to 65% when the reaction was carried out in DMF
at room temperature (entry 2). When the reaction was carried
out in dichloromethane under reflux, 18a was obtained in 34%
yield along with 24a (34%) and 25a (18%), and the combined
yield of the products increased to 80% (entry 3). The structure
of 18a was determined unambiguously by X-ray analysis as
shown in Figure 1 in the Supporting Information. The stereo-
chemistry of the C4-C5 double bond was cis and that of the
C8-C9 was trans. The reaction of the activated olefins, 3c and
3l, having an electron-donating group at the para position of
the benzene ring gave 18c and 18l, respectively, as a minor
(6) It has been confirmed that the reaction between allyltributylstannane
and PdCl2(PPh3)2 produces bis-π-allylpalladium complex. See ref 2.
(7) Recent examples using the ring-closing metathesis see: (a) Crimmins,
M. T.; Choy, A. L. J. Am. Chem. Soc. 1999, 121, 5653. (b) Fu¨rstner, A.;
Seidel, G.; Kindler, N. Tetrahedron 1999, 55, 8215. (c) Winkler, J. D.;
Holland, J. M.; Kasparec, J.; Axelsen, P. H. Tetrahedron 1999, 55, 8199.
(d) Oishi, T.; Nagumo, Y.; Hirama, M. Chem. Commun. 1998, 1041. (e)
Grubbs, R. H.; Chang, S. Tetrahedron 1998, 54, 4413.
(8) Cr(0)-promoted [6π+4π] cycloaddition: (a) Rigby, J. H. Tetrahedron
1999, 55, 4521. Rh(II)-catalyzed three-carbon-ring enlargement: (b) Oku,
A.; Ohki, S.; Yoshida, T.; Kimura, K. Chem. Commun. 1996, 1077.
(9) Intramolecular Nozaki-Hiyama reaction: (a) Luker, T.; Whitby, R.
J. Tetrahedron Lett. 1996, 37, 7661. Pd-Catalyzed cyclization: (b) Ma, S.;
Negishi, E. J. Am. Chem. Soc. 1995, 117, 6345. Co2(CO)8-promoted ether
ring formation: (c) Isobe, M.; Yenjai, C.; Tanaka, S. Synlett 1994, 916.
(10) Ni(0)-catalyzed [8+2] cycloaddition: (a) Brenner, W.; Heimbach,
P.; Ploner, K.-J.; Tho¨mel, F. Angew. Chem., Int. Ed. Engl. 1969, 8, 753.
BF3‚OEt2-promoted [7+3] cycloaddition: (b) Guo, R.; Green, J. R. Chem.
Commun. 1999, 2503.
(11) Haynes, P. Tetrahedron Lett. 1970, 3687.
(12) Manyik, R. M.; Walker, W. E.; Atkins, K. E.; Hammack, E. S
Tetrahedron Lett. 1970, 3813.
(13) (a) Ohno, K.; Mitsuyasu, T.; Tsuji, J. Tetrahedron Lett. 1971, 12,
67. (b) Ohno, K.; Mitsuyasu, T.; Tsuji, J. Tetrahedron 1972, 28, 3705.
(14) Kiji, J.; Yamamoto, K.; Tomita, H.; Furukawa, J. Chem. Commun.
1974, 506.
(16) Benn, R.; Jolly, P. W.; Mynott, R.; Raspel, B.; Schenker, G.; Schick,
K.-P.; Schroth, G. Organometallics 1985, 4, 1945. The stoichiometric
reaction of bis-π-allylpalladium complex with CO2 and SO2 was reported:
Hung, T.; Jolly, P. W.; Wilke, G. J. J. Organomet. Chem. 1980, 190, C5.
(15) Ohno, K.; Tsuji, J. Chem. Commun. 1971, 247.

Synthesis of Medium-Sized Carbocycles
J. Am. Chem. Soc., Vol. 123, No. 3, 2001 375
Table 2. Palladium-Catalyzed [n+2] Cycloadditions (n ) 4, 8, 9,
and 10) of the Activated Olefins 3 with 17a-ca
Scheme 4
17a
yields of products (%)b
[8+2] adducts [4+2] adducts
entry
3
catalyst solvent/temp
18
21
24
25
1
2
3
4
5
6
7
8
9
3a Pd(PPh3)4 THF/rt
3a Pd(PPh3)4 DMF/rt
1
7
19
40
34
32
36
10
4
24
7
2
10
18
18
12
19
14
23
10
9
3a Pd(PPh3)4 CH2Cl2/reflux 34
3c Pd(PPh3)4 CH2Cl2/reflux 10
3l Pd(PPh3)4 CH2Cl2/reflux 26
3m Pd(PPh3)4 CH2Cl2/reflux 53
3n Pd(PPh3)4 CH2Cl2/reflux 53
3o Pd(PPh3)4 CH2Cl2/reflux 53
3p Pd(PPh3)4 CH2Cl2/reflux 66
10 3q Pd(PPh3)4 CH2Cl2/reflux 61
23
17b
[9+2] adducts
entry
11
3
catalyst
solvent/temp
THF/reflux
19
22
3a Pd(PPh3)4
19
trace
6
17
14
24
20
41
35
58
54
47
48
41
12c 3a Pd2dba3‚CHCl3/4 P(OPh)3 THF/0 °C
13c 3a Pd2dba3‚CHCl3/4 P(OPh)3 THF/rt
14c 3a Pd2dba3‚CHCl3/4 P(OPh)3 THF/reflux
15c 3c Pd2dba3‚CHCl3/4 P(OPh)3 THF/reflux
18m-q in 53-66% yields, as major products (entries 6-10).
In all the cases, the stereoisomeric (trans,trans)-[8+2] cyclo-
adducts 21 (n ) 1) were not obtained.
16
17
3l Pd(PPh3)4
3p Pd(PPh3)4
THF/reflux
THF/reflux
Interesting observations in the reaction of 17a with 3a,c,l-g
are as follows: (i) in polar and coordinative solvents such as
THF and DMF, the [4+2] adducts were obtained almost
exclusively or very predominantly as observed in the previous
reactions of 14 with hetero CdZ compounds 15 (eq 3) or with
isocyanates 9, whereas the [8+2] adducts were produced
predominantly or in significant yields in a noncoordinative
solvent (CH2Cl2): (ii) in the reaction with the activated alkenes
3c and 3l, bearing an electron-donating group at the para-
position of the benzene ring, the [8+2] adducts 18c and 18l
were produced as minor products, whereas those adducts
18m-q were obtained as major products in the reaction with
the activated alkenes 3m-q bearing an electron-withdrawing
group at the para position. The difference in these reactivities
is explained later in Scheme 4, based on the structure of the
intermediate (η1,η3-octadienediyl)palladium complex.
17c
[10+2] adducts
entry
3
catalyst
solvent/temp
THF/reflux
20
23
18 3a Pd(PPh3)4
13
2
19c 3a Pd2dba3‚CHCl3/4 P(OPh)3 THF/reflux
trace
a The reactions of the activated olefins 3 with 17a-c (1.3 equiv)
were carried out in the presence of the palladium catalysts (10 mol
%). b Isolated yields based on 3. c The reaction was carried out in the
presence of the palladium catalyst (5 mol %) and the phosphine ligand
(20 mol %).
The reaction of 17b with 3a proceeded smoothly in the
presence of Pd(PPh3)4 catalyst (10 mol %) in THF under reflux
to give the [9+2] cycloaddition (endo-endo mode cycloaddi-
tion) products 19a (n ) 2) and 23a (n ) 2) in 19% and 41%
yields, respectively, and the [5+2] and [7+2] cycloaddition
(exo-exo or exo-endo mode cycloaddition) products were not
obtained (entry 11). The Pd2dba3‚CHCl3/4P(OPh)3 (5 mol %)
catalyst system was also effective for the [9+2] cycloaddition,
in which the product distribution and the combined yield of
19a and 22a were influenced by the reaction temperature. When
the reaction was carried out in the presence of Pd2dba3‚CHCl3/
4P(OPh)3 catalyst at 0 °C, the product 22a was obtained in 35%
yield along with a trace amount of 19a (entry 12). The reaction
at room temperature gave 22a in 58% yield together with 6%
yield of 19a, and the yield of 19a increased to 17% by carrying
out the reaction under reflux (entries 13 and 14). The structures
of 19a and 22a were also determined by X-ray analysis as shown
in Figures 2 and 3 in the Supporting Information. The stereo-
product, and the [4+2] cycloadducts 25c-l and 31c-l became
major products (entries 4 and 5). On the other hand, the activated
olefins 3m-q, having an electron-withdrawing group at the para
position of the benzene ring, produced the [8+2] cycloadducts

376 J. Am. Chem. Soc., Vol. 123, No. 3, 2001
Nakamura et al.
chemistry of the C4-C5 double bond of 19a was cis and that
of the C9-C10 double bond was trans (Figure 2), and the
stereochemistry of both double bonds at C4-C5 and C9-C10
of 22a was trans (Figure 3). The other 4-substituted benzyliden-
emalononitriles, 3c, 3l, and 3p, underwent the [9+2] cycload-
dition reaction with 17b in the presence of a palladium(0)
catalyst, giving the corresponding 1,1-dicyano-4-trans-9-trans-
undecadienes, 22c, 22l, and 22p, respectively, in 41-47% yields
along with the stereoisomeric 1,1-dicyano-4-cis-9-trans-undeca-
dienes, 19c, 19l, and 19p, in 14-24% yields (entries 15-17).
It should be noted that the reactions of 17b gave the [9+2]
cycloadducts selectively, and none of the [7+2] and [5+2]
adducts were obtained.
Scheme 5
Encouraged by the above results, we further examined the
[10+2] cycloaddition reaction. However, the reaction of 17c
with 3a in the presence of Pd(PPh3)4 catalyst (10 mol %) gave
small amounts of the 12-membered carbocycles, 20a and 23a
(entry 18). The use of the Pd2dba3‚CHCl3/4P(OPh)3 (5 mol %)
catalyst system gave even worse results: only trace amounts
of 20a and 23a were obtained (entry 19).
[4+2] vs [8+2] (or [4+2] vs [9+2]) Cycloaddition of Bis-
π-allylpalladium Intermediates. (1) Addition of CdZ. It is
known that the telomerization of 1,3-butadiene with aldehydes,
imines, and isocyanates proceeds regioselectively to afford the
corresponding [4+2] cycloaddition products.11-15 Tsuji13b and
Wilke17 proposed that this reaction proceeded via a bis-π-
allylpalladium intermediate generated from the butadiene dimer-
ization process as shown in eq 3. Jolly and co-workers16 studied
the intermediates in the palladium-catalyzed reactions of 1,3-
dienes and found that the reaction of (η1,η3-octadienediyl)-
palladium-phosphine complex 26 with AcOD gave η3-allylic
palladium acetate-phosphine complex 27 in which deuterium
was labeled exclusively at the C6 position (eq 6). This indicates
would take place as shown via 30, leading to 31, which upon
reductive coupling would produce the [4+2]adducts 24a and
25a. In the reaction of 3a,c,l in CH2Cl2, a pathway through the
alkene-Pd coordination in 32 (or 33) would compete with the
ordinary nucleophilic addition pathway via 30, giving a mixture
of the [8+2] and [4+2] adducts. In the case of 3m-q having
an electron-withdrawing group at the para position of the
benzene ring, the coordination of the electron-deficient alkene
to Pd(II) would become much stronger favoring a pathway via
32. Accordingly, the [8+2] adducts are obtained predominantly
over [4+2] adducts.
To further confirm the above postulate, we carried out the
reaction of excess amounts of 1,3-butadiene with 3a in the
presence of Pd(NO3)2 (2.5 mol %) and PPh3 (8 mol %) in DMF
at 80 °C for 1 d (eq 7), the same reaction conditions as those
used in the reaction of 1,3-butadiene with imines.13 A 1:1
mixture of 24a and 25a was produced in good yield, but no
[8+2] adducts were obtained most probably due to DMF
solvent. We also examined the same reaction in CH2Cl2, instead
of DMF, but the reaction was quite sluggish and after 9 d at 80
°C a messy product mixture was obtained. Accordingly, the 10-
membered carbocycles 18 can be obtained by the [8+2]
cycloaddition reaction with 17a, and cannot be obtained by the
usual butadiene-dimerization pathway.
In the reaction of 17b, the [9+2] adducts were produced and
the other adducts through [5+2] or [7+2] cycloaddition were
not obtained. In contrast to the reaction of 17a, the solvent effect
in the reaction of 17b was very small: the reaction of 3a with
17b in CH2Cl2 at room temperature in the presence of Pd2dba3‚
CHCl3/4P(OPh)3 gave the [9+2] adducts (19a and 22a) in
approximately similar yield with similar stereoisomer ratio. The
reason only [9+2] addition takes place in 17b and why solvent
effect is not observed are not clear at present. We assume that
the bis-π-allylpalladium intermediate 34 derived from 17b may
be more stable than 14 derived from 17a, and thus the
cycloaddition of 17b may proceed through 34 whereas that of
30 via 36 (Scheme 5).
that in the case of η1,η3-octadienediylpalladium complexes
electrophilic attack takes place at the C-6 position: for example,
a heteroatom of 15 (or of a coordinative solvent) would
coordinate to the palladium of 14, producing the η1,η3-
octadienediyl complex that would react with the carbon elec-
trophiles (15) at the C-6 position as shown in 28 (Scheme 4).
The C-C bond formation would give 29, which, upon reductive
elimination of Pd(0), may produce either 16 or its eight-
membered regioisomer. The reductive coupling at the C-3
position of 29 is more preferable due to thermodynamic stability
of the six-membered heterocycles 16. Similar argument can be
made for the reaction of 17a with 9 (eq 4). Consequently, in
the reaction with CdZ electrophiles, the [4+2]adducts are
obtained exclusively.
(2) Addition of Activated Alkenes. As started above, [4+2]-
addition was predominant in THF and DMF whereas [8+2]
addition became predominant (in the case of 3m-q) in
CH2Cl2. THF and DMF would coordinate to palladium of the
bis-π-allylpalladium 14, generated from 17a, to produce an
η1,η3-octadienediyl complex, or such solvents might enhance
the coordination of PPh3 to Pd of 14. Then, the nucleophilic
addition of the η1-allylic palladium to the activated alkene 3a
Conclusion
Intermolecular amphiphilic bis-allylation of activated alkenes
and imines with bis-π-allylpalladium, derived from allyltribu-
tylstannane-allyl chloride-palladium catalyst, gives the corre-
sponding 1,2-bisallylated alkanes and amines in good to high
(17) Wilke, G.; Bogdanovic; Hardt, P.; Heimbach, P.; Keim, W.; Kro¨ner,
M.; Oberkirch, W.; Tanaka, K.; Steinru¨cke. D.-C. E.; Walter, D.; Zimmer-
mann, D.-C. H. Angew. Chem., Int. Ed. Engl. 1966, 5, 151.

Synthesis of Medium-Sized Carbocycles
J. Am. Chem. Soc., Vol. 123, No. 3, 2001 377
yields. Intramolecular version of the bis-allylation using acti-
vated alkenes enables to synthesize 10- and 11-membered
carbocycles in good to high yields. Those carbocycles are not
able to be obtained through the conventional butadiene dimer-
ization method or through related methodologies.
tography on silica gel with ether. Purification by column
chromatography on silica gel with hexane/ethyl acetate (3:1)
as eluent gave 16g in 50% yield (32 mg, 0.11 mmol).
[8+2] Cycloaddition of 17a to Activated Olefins. The
reaction of 4-methoxycarbonylbenzilidenemalononitrile 3p with
17a is representative. To a solution of 3p (41 mg, 0.22 mmol)
and Pd(PPh3)4 (21 mg, 0.02 mmol) in dry CH2Cl2 (2 mL) was
added 17a (120 mg, 0.28 mmol) at 40 °C under Ar atmosphere
and the mixture was stirred for 2 d. The catalyst residue was
removed by short column chromatography on silica gel with
ether. Purification by column chromatography on silica gel with
hexane/ethyl acetate (3:1) as eluent gave 18p (47 mg, 0.15
mmol, 68% yield), 24p (4.7 mg, 0.015 mmol, 7% yield), and
25p (6.0 mg, 0.019 mmol, 9%yield).
Experimental Section
Intermolecular Amphiphilic bis-Allylation of Activated
Olefins. The reaction of phenylethylidenemalononitrile 3a,
allyltributylstannane 4, and allyl chloride 5a is representative.
To a solution of 3a (77 mg, 0.5 mmol), 4 (119 mg, 0.6 mmol),
and PdCl2(PPh3)2 (10 mg, 3 mol %) in THF (5 mL) was added
5a (49 mL, 0.6 mmol) at room temperature under Ar atmosphere
and the mixture was stirred for 13 h. The reaction was quenched
with water, and the reaction mixture was extracted with ether
and concentrated. The resulting residue was dissolved in ethyl
acetate and a saturated solution of KF was added. The mixture
was stirred for 5 h, and then extracted with ether, dried over
anhydrous magnesium sulfate, and concentrated. Purification
by column chromatography on silica gel with hexane/ethyl
acetate (10:1) as eluent gave allyl-(1-phenyl-3-butenyl)malono-
nitrile 6a in 91% yield.
[9+2] Cycloaddition of 17b to Activated Olefins. The
reaction of benzilidenmalononitrile 3a with 17b is representative.
To a solution of 3a (46 mg, 0.30 mmol), Pd2dba3CHCl3 (16
mg, 0.015 mmol), and P(OPh)3 (31 mg, 0.06 mmol) in dry THF
(2 mL) was added 17b (160 mg, 0.36 mmol) under reflux under
Ar atmosphere and the mixture was stirred for 2 d. The catalyst
residue was removed by short column chromatography on silica
gel with ether. Purification by column chromatography on silica
gel with hexane/ethyl acetate (10:1) as eluent gave 19a (35 mg,
0.16 mmol, 54% yield) and 22a (11 mg, 0.051 mmol, 17%
yield).
Intermolecular Amphiphilic bis-Allylation of Imines and
Isocyanates. The reaction of the imine 9a, allyltributylstannane
4, and allyl chloride 5a is representative.
To a solution of 9a (84 mg, 0.51 mmol) and Pd2dba3•CHCl3
(25 mg, 0.024 mmol) in DMF (2 mL) were added 4 (90 µL,
0.61 mmol) and 5a (50 µL, 0.61 mmol) at room temperature
under Ar atmosphere and the mixture was stirred for 4 d.
Palladium residue was removed by short column chromatog-
raphy on silica gel with ether. Purification by column chroma-
tography on silica gel with hexane/ethyl acetate (10:1) as eluent
gave 4-aza-4-methyl-5-(4-nitrophenyl)-1,7-octadiene 10a in 81%
yield (102 mg, 0.414 mmol).
[4+2] Cycloaddition of 17a to Isocyanates 9 g-h. The
reaction of p-toluenesulfonyl isocyanate 9g with 8-chloro-2,6-
octadienyl- tributylstannane 17a is representative. To a solution
of 9a (32 mg, 0.21 mmol) and Pd(PPh3)4 (21 mg, 0.02 mmol)
in dry CH2Cl2 (1 mL) was added 17a (110 mg, 0.25 mmol) at
40 °C under Ar atmosphere and the mixture was stirred for 2
d. The catalyst residue was removed by short column chroma-
[10+2] Cycloaddition of 17c to Activated Olefins. To a
solution of 3a (31 mg, 0.20 mmol) and Pd(PPh3)4 (22 mg, 0.02
mmol) in dry THF (2 mL) was added 17c (110 mg, 0.24 mmol)
under reflux under Ar atmosphere and the mixture was stirred
for 2 d. The catalyst residue was removed by short column
chromatography on silica gel with ether. Purification by column
chromatography on silica gel with hexane/ethyl acetate (15:1)
as eluent gave 20a (7.0 mg, 0.024 mmol, 13% yield) and 23a
(1.8 mg, 0.006 mmol, 2% yield).
Supporting Information Available: Characterization data
for new compounds 6, 10, 16, 17, 18-20, and 22-25 (PDF).
This material is available free of charge via the Internet at
http://pubs.acs.org.
JA002931G