Palladium-catalyzed and organozinc-promoted synthesis of dienes from allylic esters possessing an acyloxy or alkoxy group

Article abstract of DOI:10.1016/j.tetlet.2005.06.146

Organozinc and a Pd catalyst promoted formation of dienes from allylic esters possessing a leaving group such as acyloxy and alkoxy groups next to the allyl moiety. The reaction proceeded with high regio- and stereoselectivity when applied to secondary allylic substrates.

Full text of DOI:10.1016/j.tetlet.2005.06.146

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 5871–5875
Palladium-catalyzed and organozinc-promoted synthesis of
dienes from allylic esters possessing an acyloxy or alkoxy group
Hatsuhiko Hattori, Masahiro Katsukawa and Yuichi Kobayashi*
Department of Biomolecular Engineering, Tokyo Institute of Technology, Box B-52, Nagatsuta-cho 4259,
Midori-ku, Yokohama 226-8501, Japan
Received 6 May 2005; revised 15 June 2005; accepted 24 June 2005
Available online 15 July 2005
Abstract—Organozinc and a Pd catalyst promoted formation of dienes from allylic esters possessing a leaving group such as acyloxy
and alkoxy groups next to the allyl moiety. The reaction proceeded with high regio- and stereoselectivity when applied to secondary
allylic substrates.
Ó 2005 Elsevier Ltd. All rights reserved.
Recently, we reported a palladium-catalyzed coupling
reaction of the hydroxy-cyclopentenyl acetate with
RMgCl, in which the hydroxyl group directs the reac-
tion to follow an unusual stereochemical course.1 How-
ever, when the reaction was examined with an acyclic
substrate, the expected coupling did not take place.
Instead, the reagent promoted formation of diene in
low yield with other products (the corresponding diol
and reduction products). Herein, we present optimiza-
tion of the diene formation with a modified reagent
system consisting of an organozinc reagent and a Pd cat-
alyst, which proceeds well with allylic esters 1 and 2
possessing a leaving group such as acyloxy and alkoxy
groups next to the allyl moiety (Scheme 1). The reaction
is in sharp contrast to reactions of similar substrates
with vinylstannanes and with soft nucleophiles produc-
ing normal coupling products.2,3 In the mechanistic
point of view, the allylpalladium species generated here-
in from 1 or 2, Pd(0) cat. and RZnCl (R = Bu, Ph) is
formally of anionic character which triggers elimination
of the proximate acyloxy or alkoxy group, and thus is
different from the normal cationic allylpalladium
intermediates.4
Previously, similar substrates possessing an epoxy or
MeOCO2 group next to the allylic system have been
converted to dienes with palladium complexes.5,6
The reaction ends up with production of Pd2+ and
diene. The Pd2+ species in the latter case is recycled to
active Pd(0) species by reduction with P(O-i-Pr)3 used
as a ligand and/or methoxide derived from MeOCO2.6
On the contrary, the present reaction is promoted by a
palladium catalyst and, more importantly, is applicable
to substrates of secondary allylic esters7 with regio- and
stereoselective manners.
OR1
OR2
coupling
product(s)
R
BuZnCl
1
or PhZnCl
OR1
Pd(PPh3)4
(cat.)
R
R
3
rt, < 1 h
The present investigation was initiated with reaction of
diacetate 1a (R1 = R2 = Ac) with Bu-(or Ph-)MgCl
(3 equiv) and Pd(PPh3)4 (10 mol %) to furnish diene 3
(E/Z = 79–87:21–13) in moderate to good yields (Table
1, entries 1 and 2). None of the anticipated coupling
OR2
2
R = (CH2)2Ph
R1 = Ac, CO2Et, THP
R2 = Ac, CO2Et
1
product was observed by H NMR spectroscopy, while
Scheme 1.
the corresponding diol was obtained in 20% yield (entry
1). These results prompted examination of other
organometallics. Use of Bu- and PhZnCl provided
somewhat higher yields of 3 (entries 3 and 4), while
Et2Zn and Me3Al were less effective (entries 5 and 6).
Keywords: Palladium catalyst; Organozinc; Diene; p-Allylpalladium.
*
Corresponding author. Tel./fax: +81 45 924 5789; e-mail:
ykobayas@bio.titech.ac.jp
0040-4039/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.06.146

5872
H. Hattori et al. / Tetrahedron Letters 46 (2005) 5871–5875
Table 1. Palladium-catalyzed diene formationa
Entry
Substrate No
R1
R2
Organometallic or reagentb
Time
Yieldc (%)
Ratio of E:Z
1
2
3
4
5
6
7
8
1a
1a
1a
1a
1a
1a
1a
1b
1b
1b
1b
1c
1d
2a
2a
2b
2b
Ac
Ac
Ac
Ac
Ac
Ac
Ac
CO2Et
CO2Et
CO2Et
CO2Et
THP
TBS
Ac
Ac
Ac
Ac
Ac
Ac
Ac
Ac
CO2Et
CO2Et
CO2Et
CO2Et
Ac
Ac
Ac
Ac
BuMgCl
PhMgCl
BuZnCl
PhZnCl
Et2Zn
Me3Al
Pd(0)/P(O-i-Pr)3
BuZnCl
PhZnCl
Et2Zn
1.5 h
1 h
1 h
1 h
24 h
24 he
6 h
<30 min
<30 min
<30 min
3 h
1.5 h
24 h
<30 min
<30 min
<30 min
<30 min
58d
90
92
100
<5
65
0g
100 (99)
99 (84)
81
47
85
79:21
87:13
85:15
89:11
—
77:23
—
f
73:27
60:40
82:18
79:21
91:9
72:28
81:19
86:14
73:27
75:25
9
10
11
12
13
14
15
16
17
f
Pd(0)/P(O-i-Pr)3
BuZnCl
BuZnCl
BuZnCl
PhZnCl
BuZnCl
PhZnCl
46
100 (98)
100 (99)
100 (99)
100 (98)
Ac
C(@O)
C(@O)
a Reactions were carried out with organometallic (3 equiv) and Pd(PPh3)4 (10 mol %) in THF at rt, unless otherwise noted.
b Zinc reagents in entries 3, 4, 8, 9, and 12–17 were prepared in situ from Bu(or Ph)MgCl and ZnCl2.
c Referred to 1H NMR yields, while isolated yields are given in parentheses.
d Diol (1 with R1 = R2 = H) was co-produced with 3 in ca. 20% yield.
e 30–40 °C.
f Pd2(dba)3ÆCHCl3 (5 mol %) and P(O-i-Pr)3 (0.8 equiv) at rt.
g 1a (48%) was recovered.
The
previous
reagent
system,6
P(O-i-Pr)3/
OCO2Me
Pd2(dba)3ÆCHCl3, was ineffective (entry 7)8 (for more
Ph
Ph
OCO2Me
reactions, see below).
THF
5
6
The RZnCl/Pd cat. was applied to dicarbonate 1b,
which produced diene 3 cleanly within 30 min (usually
ca. 15 min) (entries 8 and 9). The Et2Zn/Pd cat. reagent
also afforded diene 3 (entry 10), reflecting high reactivity
of the carbonate moiety compensating the rather low
reactivity of Et2Zn in the diene formation (cf. entry 5).
56% (E only) (lit. 6)
ca. 30% (E/Z = 75 : 25) by us
rt
rt, 60 h
P(O-i-Pr)3/Pd cat.
PhZnCl/Pd cat.
rt, 0.5 h 85% (E/Z = 70 : 30)
Scheme 3.
Examination was continued to find an alkoxy leaving
group (OR1 group) in monoacetate 1 (R2 = Ac). Among
THP, TBS and TBDPS groups examined as R1, THP
showed a similar potency to the acetoxy group
(R1 = Ac) (entry 12).
in 1d (Table 1, entry 13) played its role as the leaving
group sufficiently. Diene 3 was also formed from benzyl-
oxy and methoxy substrates 4 (R2 = Bn, Me), but in
somewhat lower yields. These results imply that the
rate-determining step is the elimination of the acyloxy
or alkoxy group and not the formation of an allylpalla-
dium species.
Substrates of type 2 (R1, R2 = Ac, cyclic carbonate)
underwent the reaction within 30 min to give the same
diene 3 in good yields (entries 14–17).
We then compared the present reaction system and that
in the literature6 by using the literature substrate 5
(Scheme 3). Although 5 is reported to afford diene 6 ste-
reoselectively, the same reaction repeated by us two
times produced 6 with a 75:25 E/Z ratio in low yields
(the second line of the results in Scheme 3). On the other
hand, reaction with PhZnCl (3 equiv) and Pd(PPh3)4
(10 mol %) for 30 min afforded 6 in 85% yield with the
E/Z ratio of 70:30. The same tendency in reactivity is
described in the above paragraph with one-carbon long
substrate 1b (Table 1, entries 8 and 9 vs 11). Different
reactivity in these reagent systems was also observed
with slightly less reactive diacetate 1a as mentioned
above (Table 1, entries 3 and 4 vs 7).
Next examined is the substrate of type 4 in which the
allylpalladium is generated at the secondary position
(Scheme 2). Reactions of 4 with the THP or TBS group
as R2 completed within 2 h to afford diene 3 in good
yields with similar E/Z ratios. Noteworthy with the sub-
strate is that the TBS-oxy group which was unsuccessful
OAc
PhZnCl
OR2
Ph
Ph
THF, rt, 2 h
3
4
R2 = THP, 99%; TBS, 87%
In order to understand the reaction at the mechanistic
Scheme 2.
level, diacetate 1a was subjected to reaction with

H. Hattori et al. / Tetrahedron Letters 46 (2005) 5871–5875
5873
Pd(PPh3)4
(10 mol%)
30 min
BuZnCl (3 equiv)
Pd(PPh3)4 (10 mol%)
OC(=O)R
1a
p-Tol-ZnCl
(3 equiv)
+
C5H11
C5H11
rt, < 1 h
OC(=O)R
7a,b
+
+
p-Tol-H
20%
p-Tol
96%
3
C5H11
9 (major)
2
+
Z,Z-isomer
C5H11
100%
10
(E/Z = 73 : 27)
Scheme 4.
OC(=O)R
as above
rt, < 1 h
C5H11
C5H11
OC(=O)R
8a,b
1a
+
Ar-ZnCl
Pd(0)
Ar–Ar
+
E,E-isomer
C5H11
C5H11
11 (major)
OAc
OAc
R
9
Pd(Ar)2
R
Scheme 6.
Pd
Pd
B
Ar
Ar
A
OAc
Pd
Table 2. Diene synthesis from 7a,b and 8a,b
Entry Substrate C(@O)R C(@O)R Yielda (%) 9:10:11
R
3 + AcO
Ar-ZnCl
1
2
3
4
7a
7b
8a
8b
Ac
Ac
C(@O)
Ac
C(@O)
86
92
74
70
97:3:0
91:9:0
7:0:93
2:0:98
Ar
Ar
C
Ac
Scheme 5. Plausible pathways of the reaction. Ar = p-Tol.
a Isolated yields.
p-Tol-ZnCl (3 equiv)9 (Scheme 4), which produced
(p-Tol-)2 in 96% NMR yield with diene 3 (100%) and
volatile toluene (20%). p-Tol-OAc and/or p-Tol-Cl were
not detected by 1H NMR and TLC. These results
suggest the catalytic cycle delineated in Scheme 5.10 p-
Allyl-Pd-X derived from 1a and Pd(0) upon transmeta-
lation with Ar-ZnCl produces the p-allyl-Pd-Ar A,
which is in equilibrium with the r-allyl species B. These
species undergo complexation with another Ar-ZnCl at
a faster rate than the reductive elimination to afford an-
ionic r-allyl species C, which furnishes diene 3, AcOÀ
and (Ar)2Pd through anti-elimination.11 Reductive elim-
ination of (Ar)2Pd then produces (Ar)2 and an active
Pd(0) catalyst. Although syn-elimination is also conceiv-
able for production of 3 from C, the anti-fashion (anio-
nic mode of the elimination) is supported by the result
obtained with secondary allylic esters (vide infra).
OAc
R
R
OAc
7a
Pd(0), Bu
OAc
OAc
R
R
R
R
R
R
Pd
σ-12
Pd
σ-13
anti
elimination
R
R
The reagent system established above was applied
to secondary allylic diacetates 7a, 8a (R: Ac) and cyclic
carbonates 7b, 8b (R, R: C@O) (Scheme 6).12 As are
summarized in Table 2, trans olefins 7a,b afforded E,E
diene 9 with >91% geometrical purity in good isolated
yields. The minor product was Z,Z-isomer 10, and the
other E,Z-isomer 11 was not detected. On the other
hand, E,Z-diene 11 was derived from cis olefins 8a,b
with the minor E,E-isomer 9. Similar results were also
obtained with PhZnCl (data not shown).13
10, 3%
9, 97%
Scheme 7. Plausible mechanism for production of dienes 9 and 10. R:
C5H11, Pd: -[Pd(Bu)2]À.
observed production of dienes 9 and 10, supposing the
anti-fashion in the crucial elimination step. Since the
supposed syn-elimination from the major r-12 should
produce E,Z-diene 11 as the major product, this elimina-
tion course is unlikely to proceed. A similar pathway is
conceivable for production of E,Z-diene 11 from 8a,b
(pathway not illustrated).
A reasonable pathway and decisive intermediates for the
highly stereoselective conversion of 7a to E,E-diene 9
(major) and Z,Z-diene 10 (minor) are delineated in
Scheme 7, in which more and less stable anionic r-allyl-
palladium species r-12 and -13 are responsible for the
To demonstrate the synthetic potential of the present
reaction, the reaction was combined with a sugar to

5874
EtO2CO
H. Hattori et al. / Tetrahedron Letters 46 (2005) 5871–5875
3. (a) Tanigawa, Y.; Nishimura, K.; Kawasaki, A.; Mura-
OBn
EtO2CO
hashi, S. Tetrahedron Lett. 1982, 23, 5549–5552; (b) Genet,
J. P.; Ferroud, D. Tetrahedron Lett. 1984, 25, 3579–3582;
(c) Tsuji, J.; Shimizu, I.; Minami, I.; Ohashi, Y.; Sugiura,
T.; Takahashi, K. J. Org. Chem. 1985, 50, 1523–1529; (d)
Trost, B. M.; Tometzki, G. B.; Hung, M.-H. J. Am. Chem.
Soc. 1987, 109, 2176–2177; (e) Braun, M.; Unger, C.;
Opdenbusch, K. Eur. J. Org. Chem. 1998, 2389–2396; (f)
Nomura, N.; Tsurugi, K.; Okada, M. Angew. Chem., Int.
Ed. 2001, 40, 1932–1935.
PhZnCl
OBn OBn
14
OCO2Et
OBn OBn
15 (E only)
Pd cat.
75%
Scheme 8.
OH
4. Reviews: (a) Tsuji, J. Palladium Reagents and Catalysts;
John Wiley & Sons: New York, 2004, Chapter 4, p 431; (b)
Poli, G.; Giambastiani, G.; Heumann, A. Tetrahedron
2000, 56, 5959–5989; (c) Tsuji, J. Palladium Reagents and
Catalysts; John Wiley & Sons: Chichester, 1996, Chapter
4.2, p 290; (d) Trost, B. M.; Van Vranken, D. L. Chem.
Rev. 1996, 96, 395–422.
OH
AD-mix-β
+
R
R
R
75%
OH
17
OH
16
18
3 : 1
O
5. Keinan, E.; Sahai, M.; Kirson, I. J. Org. Chem. 1983, 48,
2550–2555.
6. (a) Trost, B. M.; Tometzki, G. B. J. Org. Chem. 1988, 53,
915–917; (b) Trost, B. M.; Tometzki, G. B. Synthesis 1991,
1235–1245.
0=C(OCCl3)2
80%
BuZnCl / Pd cat.
O
O
18
16
R
THF, rt, 20 min
77%
19
Scheme 9. Recycling procedure of minor diol to diene. R =
(CH2)4OBn.
7. Other diene syntheses through the different reaction
mechanisms: (a) Tsuji, J.; Yamakawa, T.; Kaito, M.;
Mandai, T. Tetrahedron Lett. 1978, 2075–2078; (b) Trost,
B. M.; Verhoeven, T. R.; Fortunak, J. M. Tetrahedron
Lett. 1979, 2301–2304; (c) Trost, B. M.; Fortunak, J. M.
J. Am. Chem. Soc. 1980, 102, 2841–2843; (d) Trost, B. M.;
Fortunak, J. M. D. Tetrahedron Lett. 1981, 22, 3459–3462;
(e) Mandai, T.; Matsumoto, T.; Nakao, Y.; Teramoto, H.;
Kawada, M.; Tsuji, J. Tetrahedron Lett. 1992, 33, 2549–
2552.
provide a new diene 15 from the sugar-derived com-
pound 14 in 75% yield (Scheme 8).
An application of the present reaction is shown in
Scheme 9, which provides a convenient recovery process
of unwanted regioisomeric diols produced by the Sharp-
less AD reaction14 of 1,3-dienes. Thus, AD reaction of
diene 16 (R = (CH2)4OBn) with AD-mix-b afforded
regioisomeric diols 17 and 18 in a 3:1 ratio as expected.15
After separation of the isomers, the minor 1,2-diol 18
was converted into cyclic carbonate 19, which produced
diene 16 in 77% yield with 95% E-olefin selectivity by
using the present reaction with BuZnCl. This protocol
would be especially useful when diene is prepared via
a long sequence of reactions.
8. This result (no reaction) with the less reactive acetoxy
leaving group had been predicted from the results of Ref. 6.
9. Reaction proceeded with 2 equiv of p-Tol-ZnCl, but took
6 h for the completion.
10. Other possible intermediates responsible for the diene
formation would be (1) allylzinc species produced by
transmetalation of A and/or B with ArZnCl; and (2)
r-allylpalladium species B as such. These intermediates
should produce Ar-Pd-X (X = OAc and/or Cl), which
would undergo reductive elimination to afford Ar-X and/
or transmetalation with ArZnCl to produce (Ar)2Pd and
thence (Ar)2. However, production of Ar-X was not
observed (see text). In relation to this issue, an attempted
palladium-catalyzed coupling reaction of p-Tol-Cl with
p-Tol-ZnCl did not take place under otherwise the same
reaction conditions for the diene formation, whereas a
similar reaction using p-Tol-I afforded the coupling
product, (p-Tol)2, in 70% yield. These results also support
the pathway shown in Scheme 5.
In summary, we have presented that RZnCl/Pd cat. pro-
motes formation of dienes from substrates possessing a
leaving group such as acyloxy and alkoxy groups next
to the allyl moiety. The use of RZnCl/Pd cat. is unprec-
edented. Moreover, the reaction is applicable to second-
ary substrates, thereby producing the dienes regio- and
stereoselectively.16
11. cf. b-Carbo-elimination: Harayama, H.; Kuroki, T.;
Kimura, M.; Tanaka, S.; Tamau, Y. Angew. Chem., Int.
Ed. 1997, 36, 2352–2354.
12. Isomeric purity of >95% for these substrates was con-
Acknowledgements
1
firmed by H NMR spectroscopy.
13. The literature procedure of Ref. 6 also produces internal
diene. However, the reaction takes two days and the diene
produced is a mixture of the geometrical isomers with the
E,E isomer being the major product.
This work was supported by a Grant-in-Aid for Scien-
tific Research from the Ministry of Education, Science,
Sports, and Culture, Japan.
14. (a) Kolb, H. C.; VanNieuwenhze, M. S.; Sharpless, K. B.
Chem. Rev. 1994, 94, 2483–2547; (b) Sharpless, K. B.;
Amberg, W.; Bennani, Y. L.; Crispino, G. A.; Hartung, J.;
Jeong, K.-S.; Kwong, H.-L.; Morikawa, K.; Wang, Z.-M.;
Xu, D.; Zhang, X.-L. J. Org. Chem. 1992, 57, 2768–2771.
15. Xu, D.; Crispino, G. A.; Sharpless, K. B. J. Am. Chem.
Soc. 1992, 114, 7570–7571.
References and notes
1. Hattori, H.; Abbas, A. A.; Kobayashi, Y. Chem. Commun.
2004, 884–885.
2. (a) Shipe, W. D.; Sorensen, E. J. Org. Lett. 2002, 4, 2063–
2066; (b) Chen, J.; Lin, G.-Q.; Wang, Z.-M.; Liu, H.-Q.
Synlett 2002, 1265–1268.
16. Typical procedure for the palladium-catalyzed diene
formation (Table 1, entry 8): To a solution of ZnCl2

H. Hattori et al. / Tetrahedron Letters 46 (2005) 5871–5875
5875
(73 mg, 0.535 mmol) dissolved in THF (0.7 mL) was
added n-BuMgCl (0.505 mL, 0.88 M in THF,
0.444 mmol). After 15 min at rt, Pd(PPh3)4 (17 mg,
0.015 mmol) and a solution of 1b (50 mg, 0.148 mmol)
in THF (0.3 mL) were added slowly. The reaction was
carried out at rt for 30 min and quenched by addition of
saturated NH4Cl solution. The mixture was extracted
with Et2O twice. The combined extracts were dried
(MgSO4) and concentrated in vacuo to leave an oil,
which was purified by chromatography on silica gel with
hexane as an eluent to afford diene 3 (23 mg) in 99%
yield.