Copper(I)-catalyzed reaction of acylzirconocene chloride: Cross-coupling and conjugate addition

Article abstract of DOI:10.1016/S0040-4020(02)01422-9

For the purpose of exploring a new reaction of acylzirconocene chloride as an acyl anion donor, Cu(I)-catalyzed cross-coupling and conjugate addition reactions of acylzirconocene chloride were studied. The coupling reaction with allylic or propargylic halides efficiently proceeded to yield β,γ-unsaturated ketone or allenyl ketone derivatives, respectively. The conjugated addition reaction to α,β-enones was carried out in the presence of 2 equiv. of BF₃·OEt₂ giving 1,4-diketone compounds.

Full text of DOI:10.1016/S0040-4020(02)01422-9

Tetrahedron 58 (2002) 10429–10435
Copper(I)-catalyzed reaction of acylzirconocene chloride:
cross-coupling and conjugate addition
*
Yuji Hanzawa, Kensuke Narita, Masaya Yabe and Takeo Taguchi
*
School of Pharmacy, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan
Received 4 October 2002; accepted 29 October 2002
Abstract—For the purpose of exploring a new reaction of acylzirconocene chloride as an acyl anion donor, Cu(I)-catalyzed cross-coupling
and conjugate addition reactions of acylzirconocene chloride were studied. The coupling reaction with allylic or propargylic halides
efficiently proceeded to yield b,g-unsaturated ketone or allenyl ketone derivatives, respectively. The conjugated addition reaction to
a,b-enones was carried out in the presence of 2 equiv. of BF
reserved.
3
·OEt
2
giving 1,4-diketone compounds. q 2002 Elsevier Science Ltd. All rights
1. Introduction
Cu(I)-catalyzed reactions of 1: cross-coupling with organic
6
halides and conjugate addition to a,b-enones.
The importance of an acyl anion in organic synthesis has
been well recognized and a number of ‘masked’ acyl anion
equivalents have been devised and applied to the nucleo-
1
philic acylation of organic molecules. The use of the
2. Results and discussion
masked acyl anion, however, implies that an extra step is
required to regenerate an acyl functional group in the
product. As an ‘unmasked’ acyl anion donor, an acyl-metal
species has long been studied by many research groups for
2.1. Cross-coupling reaction
The cross-coupling reaction of an acyl-metal species with
organic halides has attracted attention for the synthesis of
unsymmetrical ketone derivatives, and several acyl-metal
complexes have been employed for the purpose. In 1998,
we reported the preparation of unsymmetrical ketones
2
the introduction of acyl anion. However, the toxicity of
metal carbonyls as a starting material for the preparation of
the acyl-metal species and/or the instability of the prepared
acyl-metal species could reduce the practicability of the
acyl-metal species as a synthetic reagent.
7
through Pd-catalyzed cross-coupling reactions of 1 with
3
organic halides.
d
3
Our recent studies on the reactivity of stable acylzircono-
cene chloride complex (RCOZrCp Cl, Cp¼cylopentadienyl)
However, in the Pd-catalyzed coupling reaction of 1 with
allylic halides and/or acetate, the purification of coupling
product 2, b,g-unsaturated ketone, was hampered by
the formation of a side product (e.g. 3, Scheme 2),
a,b-unsaturated ketone, which was derived from the
isomerization of 2 during the reaction. A further exami-
nation of the catalyst in the cross-coupling reaction showed
2
4
1, which is easily available through the hydrozirconation
5
of alkene or alkyne with Schwartz reagent (Cp Zr(H)Cl)
2
and subsequent insertion of carbon monoxide, have
indicated a promising use of 1 as an unmasked acyl anion
donor (Scheme 1). We describe herein a full account on
Scheme 1.
Keywords: acylzirconocene chloride; allenyl ketone; propargylic halides.
*
Corresponding authors. Tel.: þ81-426-76-3274; fax: þ81-426-76-3257;
Scheme 2. Cu(I) catalyzed cross-coupling reaction of 1 with allylic
compounds.
e-mail: hanzaway@ps.toyaku.ac.jp
0040–4020/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(02)01422-9

10430
Y. Hanzawa et al. / Tetrahedron 58 (2002) 10429–10435
Table 1. Cu-catalyzed cross-coupling reactions of 1 with allylic compounds
a
Entry
R
R1
R2
R3
X
Cu(I)
Solv
2 Yield (%)
1
2
3
4
5
6
7
8
9
Ph(CH
1a
1a
1a
1a
1a
1a
1a
2
)
4
1a
H
H
H
H
H
H
H
H
H
H
H
CH
H
H
H
H
H
H
H
H
H
H
H
H
CH
CH
H
H
Br
Cl
I
CuI
CuI
CuI
CuI
CuI
CuI·2LiCl
CuCN·2LiCl
CuBr·SMe
CuBr
CuCl
CuI
DMF
DMF
DMF
DMF
DMF
THF
2a 91
44
76
77
–
88
87
,10
78
H
H
H
H
H
H
H
H
H
H
H
H
CH
H
OTs
OAc
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
THF
THF
2
1a
1a
DMF
DMF
DMF
DMF
DMF
DMF
DMF
10
11
12
13
14
15
84
2b 78
(E)-Ph(CH
2
)
2
CHvCH 1b
b
1a
1a
1a
1b
3
3
3
CuI
CuI
CuI
CuI
2c 91
2d 72
c
H
CH
3
2e 84
2f 47
d
3
CH
3
(
E)-crotyl bromide/(Z) crotyl bromide/3-bromo-1-butene¼73:14:13.
a
Yields are isolated and calculated from allylic compounds.
b
c
d
Reaction period; 10 h. 2cA/2cB¼1:2.
dA/2dB¼1:2.6.
Reaction period; 10 h. 2fA/2fB¼1:1.6.
2
a promising result of Cu(I) catalyst to attain the exclusive
formation of the b,g-unsaturated ketone 2 (Scheme 2).
Thus, the reaction of 1 with allyl halides in the presence of a
catalytic amount (10 mol%) of Cu(I) in DMF or THF
efficiently proceeded at 08C and completed within 1 h at 08C
to give acyl–allyl coupled products 2 in good yields. No
isomerized side product 3 was detected in the reaction
mixture (Table 1). At the time when we published our
reaction, gave 2 in a good yield (entry 11). The mild reaction
conditions of Cu(I)-catalyzed coupling reactions of 1
compared to the previously reported Pd-catalyzed reac-
3
d
tions might exert a desirable influence on the exclusive
formation of 2. The reaction of the substituted allylic halides
gave cross-coupled products in good yields albeit their low
regioselectivity (entries 12, 13, and 15). Furthermore, a
longer reaction time (10 h) was required for completion of
the reaction than the case of allyl bromide (1 h). The Cu(I)
catalyst was also efficient for the coupling of 1 with
3
f
Cu(I)-catalyzed coupling reaction, Huang et al. also
reported that Cu(I)-catalyzed cross-coupling reactions of
acylzirconocene chloride derivatives with alkynyl halides
9
propargyl halides or tosylate 4 (Scheme 3). The result is
8
gave vinyl alkynyl ketone derivatives.
listed in Table 2. The reaction of 4 with 1a afforded allenyl
ketone derivative 5a together with a trace amount of 6a
(entry 1, Table 2). The use of an increased amount (3 equiv.)
of 1a to 4 gave 1,4-dicarbonyl compound 6a as a major
product (48%) together with 5a (24%) (entry 2).
Although the examined Cu(I) salts other than CuBr·SMe2
(
entry 8) can be used as an efficient catalyst, the solubility of
a Cu(I) catalyst is important for the formation of 2. Thus, the
use of a suspension of CuX in THF decreased the product
yield (,20%). Allyl tosylate is also an excellent reactant in
the present reaction (entry 4, Table 1) while allyl acetate is
not (entry 5). a,b-Unsaturated acylzirconocene chloride 1b,
which is a poor substrate for the reported Pd-catalyzed
The formation of 5 as the sole product was attained by
utilizing 4 in excess amount (4/1¼2:1) (entries 3–7, Table
2). The reaction of the isolated 5a with 1a under identical
conditions afforded 6a in 59% yield (Scheme 4), and
the result suggests a possibility for the Cu(I)-catalyzed
conjugate addition of 1 to enone compounds (vide infra).
Scheme 3.
Table 2. Cu(I)-catalyzed coupling reaction with propargylic compounds
Scheme 4.
Entry
1
Ratio of 1/4
4
Yield (%)
The present Cu(I)-catalyzed cross-coupling reactions of 1
did not work for alkyl-, vinyl-, homoallyl- or aryl halides.
The CuI-catalyzed reaction of 1a with acetyl chloride in
DMF at 08C for 1 h gave a mixture (E/Z¼1:1) of enol
acetate 7 in 65% yield, and no reaction took place in the
absence of CuI catalyst (Scheme 5). It is very interesting to
note that treatment of 1a with a stoichiometric amount of
CuI/DMF or CuCl·2LiCl/THF afforded a-ketol 8 in 60 or
1
R
X
5
6
a
a
1
2
3
4
5
6
7
1a
1a
1a
1a
1a
1b
1b
1.5
3.0
0.5
0.5
0.5
0.5
0.5
H
Br
Br
Br
OTs
Br
Br
Br
5a 65
24
6a ,5
48
a
a
H
H
H
b
55
21
0
0
0
0
0
b
b
b
CH
H
3
5b 61
5c 52
5d 47
b
CH
3
6
8% yield, respectively (Scheme 6). Based on these
a
observations and the fact that the transmetalation of alkenyl
group in alkenylzirconocene complex from Zr to Cu
Yields are isolated and calculated from 6.
Yields are isolated and calculated from 1.
b

Y. Hanzawa et al. / Tetrahedron 58 (2002) 10429–10435
10431
a,b-unsaturated carbonyl compounds is an important tactic
for the introduction of various carbon nucleophiles to the
1
2
b-carbon of the a,b-unsaturated carbonyl compounds. As
the Cu(I)-catalyzed conjugate addition of hard organo-
metallic reagents to a,b-enones is a highly useful reaction in
modern organic synthesis, the observation described above
prompted us to examine the Cu(I)-catalyzed conjugate
addition of 1 to a,b-enones. The conjugate addition of an
unmasked acyl anion to a,b-enones is an efficient procedure
for the preparation of 1,4-dicarbonyl compounds, and we
reported the palladium-catalyzed regiochemically tunable
reactions of acylzirconocene chlorides 1 to a,b-enones by
Scheme 5.
3
c
selecting the Pd-catalyst. Besides the acylzirconocene
1
3
chloride complex, acyl-metal reagents, such as: nickel,
16
iron, cobolt, tin, or acyl-lithium cuprate reagents
1
4
15
17
have also been reported to be efficient donors of an acyl
anion in the conjugate addition to a,b-enones. The Cu(I)-
catalyzed addition of alkylzirconocene chloride complexes
(
RZrCp Cl) to a,b-enones efficiently proceeds to give
2
1
8
conjugate addition products. At the outset, the reactivity
of n-nonanoylzirconocene chloride (1c) to 1,3-diphenyl-
propenone was examined (Scheme 7), and the result is
shown in Table 3.
Scheme 6. Generation of RCOCu, a-ketol 8 and the supposed mechanism.
The 1,4-conjugate addition proceeded efficiently to give 10a
(76% yield) by the addition of CuCl·2LiCl (10 mol%) and
BF ·OEt (2 equiv.) to the reaction mixture in THF/ether
3 2
9
occurs, we consider that the present Cu(I)-catalyzed
reactions proceed through an acylcopper intermediate
(
RCOCu 9) as an active species by the acyl group transfer
(1:2), and no 1,2-addition product was isolated from the
reaction mixture (entry 3, Table 3). The reaction was
from Zr to Cu (transmetalation). Thus, the formation of 7
could be explained by the generation of a Cu-enolate via
oxy-Cu carbene, the subsequent 1,2-migration of hydrogen
atom to Cu-enolate, and the reaction with acetyl chloride as
shown in Scheme 6. The similar observation and the
mechanistic consideration have been made by Norman et al.
in the formation and reaction of acyl zinc species in ethyl
sluggish without adding BF
took place without using the Cu(I) catalyst even in the
presence of BF ·OEt . The use of BF ·OEt in less than
·OEt (entry 1), and no reaction
3
2
3
2
3
2
2 equiv. to a,b-enone decreased the yield of 10a from 76 to
53% (entry 2). In addition, in the case of more than 2 equiv.
of BF ·OEt , the yield of 10a decreased to 44% (entry 4).
3 2
1
0,11
acetate.
Besides the CuCl·2LiCl catalyst, other Cu(I) catalysts, such
as CuCN·2LiCl (65%), CuBr·SMe (42%), showed catalytic
2
2
.2. Conjugate addition
activity for the 1,4-addition (entries 5 and 6). It should be
mentioned that the use of CuI (10 mol%) in DMF as a
catalyst at 08C gave a low yield of 10a (,10%). Thus, the
presence of a CuX·2LiCl catalyst (10 mol%) and BF ·OEt
The conjugate addition of organometallic reagents to
3
2
(2 equiv.) in THF/ether (1:2) is requisite to perform the
1
2
,4-addition of 1 to a,b-enones. Although the exact role of
equiv. BF ·OEt in addition to the activation of a,b-enone
3
2
is unclear, BF ·OEt may have an influence on transiently
3
2
formed 9 to generate RCOCu·BF as suggested for RCu·BF
3
3
1
9
by Yamamoto et al. or might generate a reactive cationic
acylzirconocene species (RCOZrCp ) by the abstraction
Scheme 7.
þ
of chloride ligand. The importance of BF ·OEt for
2
2
0
3
2
Table 3. Cu(I)-catalyzed conjugate addition of 1 to 1,3-diphenylpropenone
achieving optimal chemical yield has also been reported
in the reactions of Cu(I)-catalyzed 1,4-addition of alkyl-
zirconocene chloride (RZrCp Cl) to N-acyl oxazolidi-
a
Entry
1 R
Cu(I)
BF ·OEt
3
2
Yield 10
(%)
b
(
equiv.)
2
1
4d
nones.
(
Various acylzirconocene chloride derivatives
1b–d) also afforded 1,4-adducts 10b–d (entries 7–9,
1
2
3
4
5
6
7
8
9
n-C
1c
1c
1c
1c
1c
t-Bu(CH
cyC 11CH
(E) n-C
8
H
17 1c
CuCl·2LiCl
CuCl·2LiCl
CuCl·2LiCl
CuCl·2LiCl
CuCN·2LiCl
–
10a 18
53
76
44
65
1.0
2.0
3.0
2.0
2.0
2.0
2.0
2.0
Table 3), although the product yield was low with the use
of a,b-unsaturated acylzirconocene chloride 1d (entry 9).
The present procedure (10 mol% CuX·2LiCl catalyst,
CuBr·S(CH
CuCl·2LiCl
CuCl·2LiCl
3
)
2
42
2
equiv. BF ·OEt in THF/Et O) can be applied to a variety
3 2 2
2
)
2
1d
1e
10b 61
10c 71
10d 27
of a,b-enone derivatives (Scheme 8), and the result of the
reaction of 1c is shown in Table 4.
6
H
2
6
H
13CHvCH 1f CuCl·2LiCl
Solvent: THF/ether¼1:2.
a
Cyclic and acyclic a,b-enones reacted with 1c to give
conjugate addition products 11 in fair to good yields.
10 mol% Cu(I).
Isolated yield.
b

10432
Y. Hanzawa et al. / Tetrahedron 58 (2002) 10429–10435
Table 4 were confirmed by comparing with the authentic
3
samples.
h
4
1
.2. Preparation of a solution of acylzirconocene chloride
Scheme 8.
Under an argon atmosphere, to a suspension of Cp Zr(H)Cl
2
Table 4. Conjugate addition of 1c to a,b-enones
(1.0 equiv.) in CH Cl (3 mL/mmol) was added alkene or
2 2
1
2
3
a
alkyne (2.0 equiv.) at ambient temperature. After the
mixture was stirred at the same temperature for 0.5 h, the
mixture was further stirred for 2 h under CO (1 atm). The
solution was concentrated in vacuo to dryness to give an
acylzirconocene chloride complex 1 as a pale yellow solid.
An appropriate solvent (see text) in a described amount was
added to the acylzirconocene chloride, and the solution was
used directly in the next reaction.
Entry
R
R
R
11 Yield %
1
2
3
4
5
6
7
8
Cyclohexenone
Cyclopentenone
65
43
57
65
55
72
52
–
b
Ph
H
H
H
H
H
CH
Ph
H
3
CH
CH
n-C
3
3
8
H
Ph(CH
Ph
17
CH
H
3
2 2
)
CH
3
CH
3
4
.3. General procedure for cross-coupling reaction
Reaction temperature: ambient temperature.
a
Isolated yield.
Reaction temperature: 08C.
b
All reactions were carried out by the use of 1.0 mmol
amount of allylic compounds. Under an argon atmosphere,
to a solution of acylzirconocene chloride complex 1
However, bis substitution at the b-carbon of a,b-enones
retarded the reaction (entry 8, Table 4). This reactivity is
very similar to that of the Pd-catalyzed 1,4-conjugate
addition reactions of 1 to a,b-enones. In all cases
examined, the isolated product was the 1,4-addition product,
and the 1,2-addition product was not detected in the reaction
mixture. The present Cu(I)-catalyzed 1,4-addition was
restricted to a,b-enones, and no conjugate addition reaction
occurred for a,b-unsaturated ester, -amide and -nitril
compounds.
(1.5 equiv.) in DMF or THF (10 mL) was added allyllic
halide or tosylate and a 0.1 equiv. amount of CuX or
CuX·2LiCl (a 0.5 M solution in THF) at 08C, and the
mixture was stirred for 1 or 10 h at the same temperature.
After the reaction mixture was filtered through a short
silica gel column, the filtrate was concentrated in vacuo
to dryness. The residue was purified by silica gel
column chromatography (hexanes/ethyl acetate¼60:1) to
give cross-coupling products in yields described in the
tables.
3
c
4.4. General procedure for 1,4-addition
3. Conclusion
All reactions were carried out by the use of 0.5 mmol
amount of a,b-enones. Under an argon atmosphere, a
solution of acylzirconocene chloride 1 (2.0 equiv.) in
THF/ether (1:2) (9 mL/mmol) was slowly added (1 h) to a
solution of a,b-enone (1.0 equiv.), CuCl·2LiCl (0.5 M
solution in THF, 0.1 equiv.) and BF ·OEt (2.0 equiv.) in
THF/ether (1:2) (9 mL/mmol) at 08C and the mixture was
stirred at ambient temperature overnight. After being added
aq. NaHCO , the mixture was extracted with ethyl acetate.
3
We indicated that the Cu(I)-catalyzed coupling and
conjugate addition reactions of acylzirconocene chlorides
as a donor of acyl anion proceeded efficiently under the mild
conditions. In these reactions, acylcopper species (RCOCu)
generated by the transfer of acyl group from Zr to Cu
was speculated as a reactive species. The present Cu(I)-
catalyzed reactions of acylzirconocene chloride are
complementary to the palladium-catalyzed reactions and
made possible to produce the b,g-unsaturated ketones
which are readily isomerized under the palladium-catalyzed
reaction. Thus, the results described herein indicate the
versatility of acylzirconocene chloride as an organometallic
reagent in organic synthesis.
3
2
The combined organic layer was washed with brine, dried
over MgSO , and filtered. The filtrate was concentrated to
4
dryness to give a crude product, which was purified by silica
gel column chromatography (hexane/ethyl acetate¼40:1) to
give 1,4-diketone compound.
1
4.4.1. 8-Phenyl-1-octen-4-one (2a). H NMR (400 MHz,
CDCl
4. Experimental
) d 1.58–1.67 (m, 4H), 2.43–2.48 (m, 2H), 2.60–
3
2
.64 (m, 2H), 3.14–3.16 (m, 2H), 5.13 (qd, 1H, J¼1.6,
4
.1. General
17.1 Hz), 5.17 (qd, 1H, J¼1.4, 10.2 Hz), 5.91 (tdd, 1H, J¼
1
3
7.0, 10.2, 17.1 Hz), 7.16–7.29 (m, 5H);
(100.6 MHz, CDCl
C NMR
) d 23.3, 30.9, 35.7, 42.1, 47.7, 118.7,
All anhydrous solvents and reagents except Cp Zr(H)Cl
2
3
were obtained from commercial suppliers and used without
further purification. The Schwartz reagent (Cp Zr(H)Cl)
was prepared according to the procedure reported by
Buchwald et al. H and C NMR are recorded in CDCl3
at 400 and 100 MHz, respectively. Melting points were
determined by a micro melting point apparatus and are
uncorrected. The structures of the products 11 described in
125.7, 128.3, 128.4, 130.7, 142.2, 208.6; IR (neat) n
1
1715 cm2 ; EIMS m/z 202 (M ). Anal. calcd for
þ
2
C
14
H
18O: C, 83.12; H, 8.97. Found: C, 82.96; H, 8.89.
5
1
13
1
4.4.2. (5E)-8-Phenyl-1,5-octadien-4-one (2b). H NMR
) d 2.52–2.58 (m, 2H), 2.79 (t, 2H, J¼
(400 MHz, CDCl
7.4 Hz), 3.28–3.31 (m, 2H), 5.14 (qd, 1H, J¼1.4, 17.1 Hz),
3

Y. Hanzawa et al. / Tetrahedron 58 (2002) 10429–10435
10433
5
1
1
.18 (qd, 1H, J¼1.4, 10.3 Hz), 5.93 (tdd, 1H, J¼6.9, 10.3,
4.4.9. (5E)-3,3-Dimethyl-8-phenyl-1,5-octadien-4-one
1
7.1 Hz), 6.13 (td, 1H, J¼1.5, 15.9 Hz), 6.89 (td, 1H, J¼6.8,
(2fB). H NMR (400 MHz, CDCl ) d 1.20 (s, 6H), 2.48–
3
1
3
5.9 Hz), 7.17–7.32 (m, 5H); C NMR (100.6 MHz,
2.54 (m, 2H), 2.77 (t, 2H, J¼7.4 Hz), 5.10–5.15 (m, 2H),
CDCl ) d 34.1, 34.4, 45.2, 118.6, 126.2, 128.3, 128.5,
3
5.88 (dd, 1H, J¼10.8, 17.2 Hz), 6.39 (td, 1H, J¼1.4,
13
1
1
30.1, 130.9, 140.6, 146.8, 197.9; IR (neat) n 1697, 1671,
1
15.3 Hz), 6.94 (td, 1H, J¼6.9, 15.3 Hz), 7.15–7.30 (m, 5H);
628 cm2 . Anal. calcd for C H O: C, 83.96; H, 8.05.
Found: C, 83.66; H, 7.97.
C NMR (100.6 MHz, CDCl ) d 23.4, 34.1, 34.4, 49.6,
114.5, 125.7, 126.1, 128.38, 128.42, 140.9, 142.5, 146.0,
1
4
16
3
1
2
01.3; IR (neat) n 1692, 1625 cm2 ; EIMS m/z 228 (M ).
þ
1
4
(
.4.3. 2-Methyl-9-phenyl-2-nonen-5-one (2cA). H NMR
400 MHz, CDCl ) d 1.56–1.68 (m, 4H), 1.62 (s, 3H), 1.75
HRMS calcd for C H O: 228.15141. Found: 228.15196.
16 20
3
1
(
s, 3H), 2.40–2.46 (m, 2H), 2.57–2.63 (m, 2H), 3.08 (d, 2H,
1
4.4.10. 8-Phenyl-1,2-octadien-4-one (5a). H NMR
(400 MHz, CDCl ) d 1.62–1.67 (m, 4H), 2.60–2.65 (m,
3
J¼7.2 Hz), 5.26–5.31 (m, 1H), 7.16–7.29 (m, 5H); C
NMR (100.6 MHz, CDCl ) d 18.0, 23.5, 25.7, 31.0, 35.7,
3
4H), 5.20 (d, 2H, J¼6.5 Hz), 5.76 (t, 1H, J¼6.5 Hz), 7.16–
3
1
3
4
IR (neat) n 1714 cm ; EIMS m/z 230 (M ). HRMS calcd
2.0, 42.7, 116.0, 125.7, 128.3, 128.4, 135.7, 142.2, 209.4;
2
7.29 (m, 5H); C NMR (100.6 MHz, CDCl ) d 24.2, 30.9,
3
1
þ
for C H O: 230.16706. Found: 230.16612.
35.7, 39.0, 79.3, 96.7, 125.7, 128.3, 128.4, 142.2, 200.7,
216.6; IR (neat) n 1932, 1681 cm2 ; EIMS m/z 200 (M ).
1
þ
16 22
Anal. calcd for C H O: C, 83.96; H, 8.05. Found: C,
1
83.71; H, 7.97.
4 16
1
4
NMR (400 MHz, CDCl ) d 1.21 (s, 6H), 1.54–1.62 (m,
.4.4. 3,3-Dimethyl-8-phenyl-1-octen-4-one (2cB).
H
3
4
2
H), 2.44–2.49 (m, 2H), 2.58–2.62 (m, 2H), 5.11–5.15 (m,
H), 5.90 (dd, 1H, J¼10.6, 17.6 Hz), 7.15–7.28 (m, 5H);
4.4.11. 6-Methylidene-1,12-diphenyl-5,8-dodecanedione
1
(6a). H NMR (400 MHz, CDCl ) d 1.59–1.69 (m, 8H),
3
1
3
C NMR (100.6 MHz, CDCl ) d 23.5, 23.7, 31.0, 35.8,
3
2.49–2.53 (m, 2H), 2.60–2.65 (m, 4H), 2.71–2.74 (m, 2H),
3.32 (s, 2H), 5.81 (s, 1H), 6.12 (s, 1H), 7.15–7.18 (m, 10H);
37.2, 50.8, 114.2, 125.7, 128.3, 128.4, 142.4, 142.6, 212.9;
IR (neat) n 1710 cm . Anal. calcd for C H O: C, 83.43;
H, 9.63. Found: C, 83.16; H, 9.45.
21
13
C NMR (100.6 MHz, CDCl ) d 23.3, 24.0, 30.9, 31.0,
3
1
6
22
35.7, 35.8, 37.0, 42.6, 45.1, 125.7, 127.1, 128.3, 128.4,
2
1
142.2, 142.9, 200.9, 207.5; IR (neat) n 1716, 1677 cm
EIMS m/z 362 (M ). Anal. calcd for C H O : C, 82.83; H,
;
1
þ
8.34. Found: C, 82.66; H, 8.36.
4.4.5. 9-Phenyl-2-nonen-5-one (E,Z-mixture) (2dA). H
NMR (300 MHz, CDCl ) d 1.57–1.70 (m, 9H), 2.42–2.48
2
5 30 2
3
(
(
3
2
m, 2H), 2.58–2.62 (m, 2H), 5.49–5.70 (m, 2H), 7.13–7.32
1
3
1
m, 5H); C NMR (75.5 MHz, CDCl ) d 18.0, 23.4, 31.0,
3
4.4.12. 3-Methyl-8-phenyl-1,2-octadien-4-one (5b).
NMR (400 MHz, CDCl ) d 1.58–1.69 (m, 4H), 1.78 (t,
H
5.7, 42.0, 46.8, 123.1, 125.7, 128.3, 128.4, 129.6, 142.2,
2
3
1
þ
09.4; IR (neat) n 1712 cm ; EIMS m/z 216 (M ). HRMS
3H, J¼3.0 Hz), 2.59–2.64 (m, 2H), 2.65–2.70 (m, 2H),
1
3
calcd for C H O: 216.15141. Found: 216.15091.
15 20
5.10 (q, 2H, J¼3.0 Hz), 7.15–7.29 (m, 5H); C NMR
100.6 MHz, CDCl ) d 13.1, 24.7, 31.0, 35.7, 38.7, 78.4,
3
(
1
4
.4.6. 3-Methyl-8-phenyl-1-octen-4-one (2dB). H NMR
103.6, 125.7, 128.3, 128.4, 142.3, 201.4, 216.3; IR (neat) n
1678 cm2 ; EIMS m/z 214 (M ). HRMS calcd for
1
þ
(
400 MHz, CDCl ) d 1.17 (t, 3H, J¼6.8 Hz), 1.56–1.66 (m,
3
4
1
1
H), 2.40–2.55 (m, 2H), 2.59–2.63 (m, 2H), 3.15–3.22 (m,
H), 5.13 (td, 1H, J¼1.0, 10.3 Hz), 5.15 (td, 1H, J¼1.2,
7.3 Hz), 5.79 (ddd, 1H, J¼8.2, 10.3, 17.3 Hz), 7.15–7.29
C H O: 214.13576. Found: 214.13549.
15 18
1
4.4.13. (5E)-8-Phenyl-1,2,5-octatrien-4-one (5c). H NMR
(400 MHz, CDCl ) d 2.52–2.58 (m, 2H), 2.79 (t, 2H,
1
3
(
m, 5H); C NMR (100.6 MHz, CDCl ) d 15.8, 23.3, 31.0,
3
3
3
2
5.8, 40.5, 51.3, 116.8, 125.7, 128.3, 128.4, 137.6, 142.3,
2
J¼7.4 Hz), 5.24 (d, 2H, J¼6.5 Hz), 5.90 (t, 1H, J¼6.5 Hz),
1
þ
11.3; IR (neat) n 1714 cm ; EIMS m/z 216 (M ). HRMS
6.57 (td, 1H, J¼1.4, 15.5 Hz), 6.96 (td, 1H, J¼6.8, 15.5 Hz),
1
3
calcd for C H O: 216.15141. Found: 216.15119.
1
7.17–7.31 (m, 5H); C NMR (100.6 MHz, CDCl ) d 34.1,
3
5
20
34.4, 79.5, 96.8, 126.1, 128.3, 128.5, 140.8, 146.3, 188.7,
216.5; IR (neat) n 1669, 1622 cm ; EIMS m/z 198 (M ).
1
21 þ
HRMS calcd for C H O: 198.104465. Found: 198.104331.
4
(
.4.7. 2-Methyl-8-phenyl-1-octen-4-one (2e). H NMR
400 MHz, CDCl ) d 1.57–1.67 (m, 4H), 1.74 (s, 3H),
3
14 14
2
.44–2.50 (m, 2H), 2.60–2.64 (m, 2H), 3.08 (s, 2H), 4.80
1
3
(s, 1H), 4.93 (s, 1H), 7.16–7.29 (m, 5H); C NMR
(100.6 MHz, CDCl ) d 22.6, 23.4, 30.9, 35.7, 41.7, 52.2,
4.4.14. (5E)-3-Methyl-8-phenyl-1,2,5-octatrien-4-one
1
(5d). H NMR (400 MHz, CDCl ) d 1.85 (t, 3H, J¼
3
3
1
14.9, 125.7, 128.3, 128.4, 139.3, 142.2, 208.7; IR (neat) n
2.9 Hz), 2.50–2.56 (m, 2H), 2.78 (t, 2H, J¼7.4 Hz), 5.14
(q, 2H, J¼2.9 Hz), 6.76 (td, 1H, J¼1.3, 15.4 Hz), 6.93
714 cm2 ; EIMS m/z 216 (M ). Anal. calcd for C H O:
1
þ
1
C, 83.28; H, 9.32. Found: C, 93.01; H, 9.24.
15 20
1
3
(td, 1H, J¼6.8, 15.4 Hz), 7.17–7.31 (m, 5H); C NMR
100.6 MHz, CDCl ) d 13.4, 34.0, 34.5, 78.7, 104.4, 125.7,
3
(
4
.4.8. (6E)-2-Methyl-9-phenyl-2,6-nonadien-5-one (2fA).
H NMR (400 MHz, CDCl ) d 1.63 (s, 3H), 1.75 (d, 3H,
126.1, 128.37, 128.44, 141.0, 145.2, 189.6, 216.3; IR (neat)
21
1
þ
C H O: 212.120115. Found: 212.119156.
n 1667, 1624 cm ; EIMS m/z 212 (M ). HRMS calcd for
3
J¼1.0 Hz), 2.51–2.57 (m, 2H), 2.79 (t, 2H, J¼7.4 Hz),
1
5 16
3
.21 (d, 2H, J¼7.1 Hz), 5.27–5.31 (m, 1H), 6.12 (td, 1H,
1
J¼1.5, 15.8 Hz), 6.87 (td, 1H, J¼6.9, 15.8 Hz), 7.17–7.31
4.4.15. (E)-5-Phenyl-1-pentenyl acetate (E-7). H NMR
(400 MHz, CDCl ) d 1.66–1.76 (m, 2H), 2.04 (q, 2H,
1
3
(
m, 5H); C NMR (100.6 MHz, CDCl ) d 18.1, 25.8,
3
3
3
1
4.1, 34.4, 40.3, 116.2, 126.2, 128.4, 128.5, 130.2, 135.6,
2
J¼6.8 Hz), 2.12 (s, 3H), 2.63 (t, 2H, J¼7.6 Hz), 5.43 (td,
13
1
40.7, 146.2, 198.6; IR (neat) n 1718 cm ; EIMS m/z 228
1H, J¼7.6, 12.4 Hz), 7.08 (d, 1H, J¼12.4 Hz), 7.16–7.30
þ
28.15101.
(
M ). HRMS calcd for C H O: 228.15141. Found:
6
(m, 5H); C NMR (100.6 MHz, CDCl ) d 20.7, 26.8, 31.2,
35.2, 114.5, 125.8, 128.3, 128.4, 135.8, 142.1, 168.3; IR
1
20
3
2

10434
Y. Hanzawa et al. / Tetrahedron 58 (2002) 10429–10435
þ
(
neat) n 2933, 1756, 1222 cm21; EIMS m/z 204 (M ).
HRMS calcd for C H O : 204.11503. Found: 204.11566.
1.43 (m, 8H), 2.14 (ddd, 2H, J¼14.8, 7.2, 1.4 Hz), 3.15 (dd,
1H, J¼17.9, 4.1 Hz), 4.05 (dd, 1H, J¼17.9, 9.6 Hz), 4.63
13
1
3 16 2
(
dd, 1H, J¼9.6, 4.1 Hz), 6.16 (dt, 1H, J¼15.7, 1.4 Hz), 6.94
1
4
(
(
1
(
.4.16. (Z)-5-Phenyl-1-pentenyl acetate (Z-7). H NMR
400 MHz, CDCl ) d 1.68–1.76 (m, 2H), 2.13 (s, 3H), 2.19
(dt, 1H, J¼15.7, 7.2 Hz), 7.23–7.97 (m, 10H); C NMR
(100.6 MHz, CDCl ) d 14.0, 22.5, 27.9, 28.8, 31.5, 32.4,
3
3
dq, 2H, J¼1.5, 7.4 Hz), 2.64 (t, 2H, J¼7.6 Hz), 4.89 (dt,
42.4, 51.5, 127.3, 128.1, 128.4, 128.5, 128.8, 129.1, 133.1,
2
1
H, J¼6.5, 7.4 Hz), 7.03 (td, 1H, J¼1.5, 6.5 Hz), 7.16–7.30
136.7, 138.6, 148.5, 198.0, 198.1; IR (neat) n 1685 cm ;
EIMS m/z 348 (M ). HRMS calcd for C H O :
1
3
þ
348.208930. Found: 348.207123.
m, 5H); C NMR (100.6 MHz, CDCl ) d 20.7, 23.9, 30.8,
3
24 28 2
3
(
5.3, 113.7, 125.7, 128.3, 128.5, 134.4, 142.2, 168.1; IR
2
1
þ
HRMS calcd for C H O : 204.11503. Found: 204.11566.
neat) n 2933, 1756, 1222 cm ; EIMS m/z 204 (M ).
1
3 16 2
1
4
NMR (400 MHz, CDCl ) d 1.50–1.82 (m, 10H), 2.37–
.4.17. 6-Hydroxy-1,10-diphenyl-5-decanone (8).
H
References
3
2
4
.51 (m, 2H), 2.58–2.64 (m, 4H), 3.44 (d, 1H, J¼4.9 Hz),
1. Grobel, B. T.; Seebach, D. Synthesis 1977, 357.
1
3
.11–4.15 (m, 1H), 7.16–7.30 (m, 10H); C NMR
2. Saalfrank, R. W.; 4th ed. Acyl Anionen und deren Derivate in
Methoden der Organischen Chemie (Houben-Weyl), 1993;
Vols. E–19d. p 567, and references cited therein.
(
100.6 MHz, CDCl ) d 23.2, 24.6, 30.9, 31.2, 33.6, 35.7,
3
3
2
5.8, 37.7, 76.2, 125.8, 125.9, 128.3, 128.4, 141.9, 142.3,
2
1
12.1; IR (neat) n 3474 (broad), 3026, 1708 cm ; EIMS
þ
3. (a) Hanzawa, Y. In Titanium and Zirconium in Organic
Synthesis, Marek, I., Ed.; Wiley/VCH: Weinheim, 2002; p
149. (b) Harada, S.; Taguchi, T.; Tabuchi, N.; Narita, K.;
Hanzawa, Y. Angew. Chem., Int. Ed. Engl. 1998, 37, 1696.
(c) Hanzawa, Y.; Tabuchi, N.; Taguchi, T. Tetrahedron Lett.
1998, 39, 8141. (d) Hanzawa, Y.; Tabuchi, N.; Taguchi, T.
Tetrahedron Lett. 1998, 39, 6249. (e) Hanzawa, Y.; Tabuchi,
N.; Saito, K.; Noguchi, S.; Taguchi, T. Angew. Chem., Int. Ed.
Engl. 1999, 38, 2395. (f) Hanzawa, Y.; Narita, K.; Taguchi, T.
Tetrahedron Lett. 2000, 41, 109. (g) Kakuuchi, A.; Taguchi,
T.; Hanzawa, Y. Tetrahedron Lett. 2001, 42, 1547.
(h) Hanzawa, Y.; Tabuchi, N.; Narita, K.; Kakuuchi, A.;
Yabe, M.; Taguchi, T. Tetrahedron 2002, 58, 7559.
m/z 324 (M ). HRMS calcd for C H O : 324.208930.
2 28 2
Found: 324.210398.
2
4
.4.18. 1,3-Diphenyl-1,4-dodecanedione (10a). Clear oil,
1
H NMR (400 MHz, CDCl ) d 0.86 (t, 3H, J¼7.1 Hz),
3
1
.19–1.28 (m, 10H), 1.50–1.55 (m, 2H), 2.42–2.64 (m,
H), 3.11 (dd, 1H, J¼18.0, 3.7 Hz), 4.03 (dd, 1H, J¼18.0,
0.1 Hz), 4.42 (dd, 1H, J¼10.1, 3.7 Hz), 7.26–7.55 (m,
2
1
8
1
1
1
1
3
H), 7.94–7.96 (m, 2H); C NMR (100.6 MHz, CDCl ) d
3
4.1, 22.6, 23.6, 29.0, 29.1, 29.3, 31.8, 41.8, 42.4, 53.3,
27.5, 128.1, 128.4, 128.6, 129.1, 133.2, 136.6, 138.3,
98.3, 209.5; IR (neat) n 1685, 1627 cm ; EIMS m/z 350
þ
2
1
(M ). Anal. calcd for C H O : C, 82.24; H, 8.63. Found:
2
C, 82.10; H, 8.78.
4. Bertelo, C. A.; Schwartz, J. Am. Chem. Soc. 1975, 97, 228.
5. It has been reported that the reactivity of alky- or
alkenylziconocene chloride derived from the hydrozirconation
of alkene or alkyne by Schwartz reagent would be altered by
the preparative method of the employed Schwartz reagent.
That is, contamination of the Schwartz reagent would have a
serious effect on the subsequent reactivity of the derived
zirconocene complexes. See Ref. 17a. To avoid the uncer-
tainty, the Schwartz reagent prepared by the Buchwald’s
procedure was employed throughout the present reactions.
(a) Buchwald, S. L.; LaMaire, S. J.; Nielsen, R. B.; Watson,
B. T.; King, S. M. Tetrahedron Lett. 1987, 28, 3895.
(b) Buchwald, S. L.; LaMaire, S. J.; Nielsen, R. B.; Watson,
B. T.; King, S. M. Org. Synth. 1993, 71, 77.
4 30 2
4
Colorless crystals, mp 51.0–52.08C. H NMR (400 MHz,
.4.19. 7,7-Dimethyl-1,3-diphenyl-1,4-octanedione (10b).
1
CDCl ) d 0.75 (s, 9H), 1.31 (ddd, 1H, J¼13.7, 11.3, 5.2 Hz),
3
1
.55 (ddd, 1H, J¼13.7, 11.3, 5.2 Hz), 2.40 (ddd, 1H,
J¼16.5, 11.2, 5.1 Hz), 2.54 (ddd, 1H, J¼16.5, 11.2, 5.1 Hz),
3
1
1
3
1
1
.07 (dd, 1H, J¼18.0, 3.7 Hz), 4.00 (dd, 1H, J¼18.0,
0.1 Hz), 4.42 (dd, 1H, J¼10.1, 3.7 Hz), 7.20–7.95 (m,
1
3
0H); C NMR (100.6 MHz, CDCl ) d 29.0, 29.9, 37.3,
3
7.5, 42.3, 53.4, 126.6, 127.5, 128.0, 128.3, 128.5, 129.0,
29.5, 133.1, 136.6, 138.3, 198.1, 209.8; IR (neat) n 1713,
682 cm2 ; EIMS m/z 323 (M þ1). Anal. calcd for
1
þ
C H O : C, 81.95; H, 8.13. Found: C, 81.72; H, 8.14.
22 26 2
6. For a preliminary report on some aspects of the present study,
see Ref. 3f.
4
.4.20. 5-Cyclohexyl-1,3-diphenyl-1,4-pentanedione
1
7. (a) Sakurai, H.; Tanabe, K.; Narasaka, K. Chem. Lett. 1999,
309. (b) Flood, T. O.; Sarhangi, A. Tetrahedron Lett. 1977, 44,
3861. (c) Verlhac, J.-B.; Chanson, E.; Jousseaume, B.;
Quintard, J.-P. Tetrahedron Lett. 1985, 26, 6075. (d) Kosugi,
M.; Naka, H.; Harada, S.; Sano, H.; Migita, T. Chem. Lett.
1987, 1371.
(
(
3
10c). Colorless crystals, mp 73.0–75.08C. H NMR
400 MHz, CDCl ) d 0.60 (ddd, 1H, J¼24.4, 12.7,
3
.4 Hz), 0.85 (ddd, 1H, J¼24.4, 12.7, 3.4 Hz), 0.93–1.28
(
1
(
4
1
m, 3H), 1.40–1.67 (m, 5H), 1.70–1.85 (m, 1H), 2.25 (dd,
H, J¼16.7, 7.4 Hz), 2.43 (dd, 1H, J¼16.7, 7.4 Hz), 3.03
dd, 1H, J¼18.0, 3.7 Hz), 3.97 (dd, 1H, J¼18.0, 10.0 Hz),
8. Sun, A.-H.; Huang, X. Heteroatom. Chem. 2000, 11, 91.
9. Formation of allenyl compounds in the CuCl-mediated
.33 (dd, 1H, J¼10.0, 3.7 Hz), 7.18–7.89 (m, 10H);
3
2
reaction of sp -C zirconacycles with propargyl halides has
C NMR (100.6 MHz, CDCl ) d 26.0, 26.1, 26.2, 32.7,
3
3
1
3.1, 33.2, 42.2, 49.4, 53.8, 127.4, 128.0, 128.4, 128.5,
29.0, 133.1, 136.6, 138.1, 198.2, 208.6; IR (neat) n 1714,
been demonstrated. (a) Takahashi, T.; Tsai, F.-Y.; Li, Y.;
Wang, H.; Kondo, Y.; yamanaka, M.; Nakajima, K.; Kotora,
M. J. Am. Chem. Soc. 2002, 124, 5059. (b) Kotora, M.;
Noguchi, Y.; Takahashi, T. Collect. Czech. Chem. Commun.
684 cm2 ; EIMS m/z 334 (M ). Anal. calcd for C H O :
1
þ
1
C, 82.60; H, 7.84. Found: C, 82.30; H, 7.90.
23 26 2
1
10. Chemla, F.; Normant, J. F. Tetrahedron 1997, 53, 17265.
999, 64, 1119.
1
4
.4.21. (E)-1,3-Diphenyl-5-dodecene-1,4-dione (10d). H
NMR (400 MHz, CDCl ) d 0.85 (t, 3H, J¼7.1 Hz), 1.18–
11. One of the reviewers pointed out the mechanistic aspects for
3

Y. Hanzawa et al. / Tetrahedron 58 (2002) 10429–10435
10435
the present Cu(I)-catalyzed coupling reactions with allylic
halides: (1) an intervention of the oxyCu carbene as an actual
reactive species, and (2) stereochemical aspects of the
products. The reviewer suggested the possibility for the
formation of cyclopropyl alkoxide by the addition of the oxyCu
carbene species to the double bond of allylic halides and
subsequent elimination of the halogen giving products 2. We
assume that the present cross-coupling reactions would
proceed through the nucleophilic attack of acyl-Cu 9 to the
allylic halide, because of the recovery of starting materials in
the reactions of homoallylic halide derivatives. However, we
must await further studies to describe a detailed mechanism
for the reaction. We appreciate the reviewer for generous
suggestions, and the reaction mechanism will be reported in
due course.
14. Cooke, Jr. M. P.; Parlman, R. M. J. Am. Chem. Soc. 1977, 99,
5222.
15. Hegedus, L. S.; Perry, J. Org. Chem. 1985, 50, 4955.
16. Shirakawa, E.; Yamamoto, Y.; Nakao, Y.; Tsuchimoto, T.;
Hiyama, T. Chem. Commun. 2001, 1926.
17. (a) Lipshutz, B. H.; Elworthy, T. R. Tetrahedron Lett. 1990,
31, 477. (b) Li, N.; Yu, S.; Kabalka, G. W. Organometallics
1999, 18, 1811. (c) Hui, R. C.; Seyferth, D. J. Am. Chem. Soc.
1985, 107, 4451. (d) Seyferth, D.; Hui, R. C. J. Am. Chem. Soc.
1985, 107, 4551. (e) Seyferth, D.; Hui, R. C. Tetrahedron Lett.
1986, 27, 1473.
18. (a) Wipf, P.; Smitrovich, J. H. J. Org. Chem. 1991, 56, 6494.
(b) Wipf, P.; Xu, W.; Smitrovich, J. H.; Lehmann, R.;
Venanzi, L. M. Tetrahedron 1994, 50, 1935. (c) Wipf, P.;
Takahashi, H. Chem. Commun. 1996, 2675.
1
1
2. Kozlowski, J. A. In Comprehensive Organic Synthesis, Trost,
B. M., Fleming, I., Eds.; Pergamon: Oxford, 1991; p 169 and
the references cited therein.
19. (a) Yamamoto, Y.; Yamamoto, S.; Yatagai, H.; Ishihara, Y.;
Maruyama, K. J. Org. Chem. 1982, 47, 119. (b) Yamamoto,
Y.; Maruyama, K. J. Am. Chem. Soc. 1978, 100, 3240.
20. Jordan, R. F. Adv. Organomet. Chem. 1991, 32, 325.
3. Corey, E. J.; Hegedus, L. S. J. Am. Chem. Soc. 1969, 91, 4926.