Cross-coupling reaction of α-chloroketones and organotin enolates catalyzed by zinc halides for synthesis of γ-diketones

Article abstract of DOI:10.1021/ja0258172

The reaction of tin enolates 1 with α-chloro- or bromoketones 2 gave γ-diketones (1,4-diketones) 3 catalyzed by zinc halides. In contrast to the exclusive formation of 1,4-diketones 3 under catalytic conditions, uncatalyzed reaction of 1 with 2 gave aldol-type products 4 through carbonyl attack. NMR study indicates that the catalyzed reaction includes precondensation between tin enolates and α-haloketones providing an aldol-type species and their rearrangement of the oxoalkyl group with leaving halogen to produce 1,4-diketones. The catalyst, zinc halides, plays an important role in each step. The carbonyl attack for precondensation is accelerated by the catalyst as Lewis acid and the intermediate zincate promotes the rearrangement by releasing oxygen and bonding with halogen. Various types of tin enolates and α-chloro and bromoketones were applied to the zinc-catalyzed cross-coupling. On the other hand, the allylic halides, which have no carbonyl moiety, were inert to the zinc-catalyzed coupling with tin enolates. The copper halides showed high catalytic activity for the coupling between tin enolates 1 and organic halides 7 to give γ,δ-unsaturated ketones 8 and/or 9. The reaction with even chlorides proceeded effectively by the catalytic system.

Full text of DOI:10.1021/ja0258172

Published on Web 05/23/2002
Cross-Coupling Reaction of r-Chloroketones and Organotin
Enolates Catalyzed by Zinc Halides for Synthesis of
γ-Diketones
Makoto Yasuda, Shoki Tsuji, Yusuke Shigeyoshi, and Akio Baba*
Contribution from the Department of Molecular Chemistry, Graduate School of Engineering,
Osaka UniVersity, 2-1 Yamadaoka, Suita, Osaka 565-0871, Japan
Received February 5, 2002
Abstract: The reaction of tin enolates 1 with R-chloro- or bromoketones 2 gave γ-diketones (1,4-diketones)
3 catalyzed by zinc halides. In contrast to the exclusive formation of 1,4-diketones 3 under catalytic
conditions, uncatalyzed reaction of 1 with 2 gave aldol-type products 4 through carbonyl attack. NMR study
indicates that the catalyzed reaction includes precondensation between tin enolates and R-haloketones
providing an aldol-type species and their rearrangement of the oxoalkyl group with leaving halogen to
produce 1,4-diketones. The catalyst, zinc halides, plays an important role in each step. The carbonyl attack
for precondensation is accelerated by the catalyst as Lewis acid and the intermediate zincate promotes
the rearrangement by releasing oxygen and bonding with halogen. Various types of tin enolates and R-chloro-
and bromoketones were applied to the zinc-catalyzed cross-coupling. On the other hand, the allylic halides,
which have no carbonyl moiety, were inert to the zinc-catalyzed coupling with tin enolates. The copper
halides showed high catalytic activity for the coupling between tin enolates 1 and organic halides 7 to give
γ,δ-unsaturated ketones 8 and/or 9. The reaction with even chlorides proceeded effectively by the catalytic
system.
Scheme 1. Cross-Coupling of Carbonylmethyl Units
Introduction
A metal-catalyzed cross-coupling reaction through carbon-
carbon bond formation is an important and powerful method
for organic synthesis.1 In general, organometallic compounds
and organic halides (or related compounds) are often the
coupling partners in this type of reaction. 1,4-Diketones (γ-
diketones) are widely used as synthetic building blocks for
further elaboration into furans, cyclopentenones, or pyrroles.2
In terms of applicability, the most straightforward method for
their preparation would be cross-coupling of different car-
bonylmethyl units, namely, carbonylmethyl anion and cation
equivalents (Scheme 1). Although a number of homo-coupling
reactions of carbonylmethyl radicals,3 metal enolates,4 or R-
halocarbonyls5 were reported, the cross-coupling of carbonyl-
methyl units is still a challenging problem.6 One main reason
for the difficulty in the cross-coupling is ascribed to lack of
appropriate compounds as carbonylmethyl cation equivalents.
R-Halocarbonyls might be a typical carbonylmethyl cation
equivalent, but they have a reactive site at the carbonyl carbon
as well as a halogeno moiety.7 This situation leads to a serious
problem in chemoselectivity. In fact, Stille reported that the Pd-
catalyzed reaction of metal enolate with R-bromoketone afforded
keto oxirane that is formed through carbonyl addition.8 Thus,
many groups have developed different types of carbonylmethyl
cation equivalents masked at the carbonyl moiety to avoid the
undesired reaction for preparation of 1,4-diketones.9 A versatile
process to access 1,4-diketones is now the conjugate acylation
of enones, and a variety of acyl anion equivalents have been
developed.10
* Corresponding author. E-mail: baba@ap.chem.eng.osaka-u.ac.jp.
(1) Diederich, F., Stang, P. J., Eds. Metal-catalyzed Cross-coupling Reactions;
Wiley-VCH: Weinheim, Germany, 1998.
(2) (a) Bosshard, P.; Eugster, C. H. AdV. Heterocycl. Chem. 1966, 7, 384-
387. (b) Ellison, R. A. Synthesis 1973, 397-412. (c) Baltazzi, E.; Krimen,
L. I. Chem. ReV. 1963, 63, 511-556.
(3) Kharasch, M. S.; Mcbay, H. C.; Urry, W. H. J. Am. Chem. Soc. 1948, 70,
1269-1274.
(4) (a) Rathke, M. W.; Lindert, A. J. Am. Chem. Soc. 1971, 93, 4605-4606.
(b) Ito, Y.; Konoike, T.; Harada, T.; Saegusa, T. J. Am. Chem. Soc. 1977,
99, 1487-1493. (c) Moriarty, R.; Prakash, O.; Duncan, M. P. J. Chem.
Soc., Perkin Trans. 1 1987, 559-561. (d) Fujii, T.; Hirao, T.; Ohshiro, Y.
Tetrahedron Lett. 1992, 33, 5823-5826. (e) Paquette, L. A.; Bzowej, E.
I.; Branan, B. M.; Stanton, K. J. J. Org. Chem. 1995, 60, 7277-7283.
(5) (a) Chassin, C.; Schmidt, E. A.; Hoffmann, H. M. R. J. Am. Chem. Soc.
1974, 96, 606-608. (b) De Kimpe, N.; Yao, Z.-P.; Schamp, N. Tetrahedron
Lett. 1986, 27, 1707-1710. (c) Iyoda, M.; Sakaitani, M.; Kojima, A.; Oda,
M. Tetrahedron Lett. 1985, 26, 3719-3722.
(6) The cross-coupling into unsymmetric 1,4-diketones necessitated strictly
controlled conditions. References 4b and 4d.
(7) De Kimpe, N.; Verhe´, R. The Chemistry of R-Haloketones, R-Haloaldehydes
and R-Haloimines; Patai, S., Rappoport, Z., Eds.; John Wiley & Sons:
Chichester, UK, 1988.
(8) Pri-Bar, I.; Pearlman, P. S.; Stille, J. K. J. Org. Chem. 1983, 48, 4629-
4634.
9
7440
J. AM. CHEM. SOC. 2002, 124, 7440-7447
10.1021/ja0258172 CCC: $22.00 © 2002 American Chemical Society

Cross-Coupling Reaction of R-Chloroketones and Organotin Enolates
A R T I C L E S
Table 1. Uncatalyzed Reaction of Tin Enolate 1a with
We have been studying the coupling reaction of tin enolates
with R-bromocarbonyls in the presence of an equimolar amount
of a ligand to the tin center.11 In this system, highly coordinated
tin enolates are generated which show high nucleophilicity for
halide selective coupling.12 However, there still remain problems
to be solved: (1) catalytic reactions, (2) use of chloroketones,
(3) use of cyclic haloketone, and (4) high chemoselectivity are
required.13 Recently, much attention has been focused on the
metal-catalyzed cross-coupling reactions with organic chlorides,
which are more available, stable, and cheap but less reactive
than bromides or iodides that are commonly used as coupling
partners.14 In this paper, we report the first successful metal-
catalyzed cross-coupling of different carbonylmethyl units using
chloroketones as a cationic partner.15 This method directly leads
to a wide variety of 1,4-dicarbonyl compounds under mild
conditions. The carbonyl moiety in chloroketone acts as a
directing group for selective C-C bond formation at the chloride
site. Furthermore, the metal-catalyzed coupling with allylic
halides including chlorides is achieved to afford γ,δ-unsaturated
ketones.
R-Chloroketone 2a-ca
1
2
entry
R
R
yield/%
1
2
3
2a
2b
2c
Ph
Me
-(CH2)4-
H
H
0 (3aa)
0 (3ab)
0 (3ac)
>99 (4aa)
62 (4ab)
>99 (4ac)
a All reactions were carried out in THF (1 mL) with tin enolate 1a (2.0
mmol) and chloroketone 2 (1.0 mmol) at 40 °C for 6 h.
Table 2. Effects of Catalysts in the Reaction of Tin Enolate 1a
with R-Chloroketone 2a-ca
Results and Discussion
1
2
entry
R
R
catalyst
time/h
product
yield/%
1
2
3
4
5
6
7
8
9
2a
2a
2a
2a
2a
2a
2a
2a
2b
2c
Ph
H
H
H
H
H
H
H
H
H
LiCl
4
3
2
1.5
6
2
2
4
2
3aa
3aa
3aa
3aa
3aa
3aa
3aa
3aa
3ab
3ac
16b
17b
10c
40b
31b
>99
72
72
64
82
Reaction of Tin Enolates with r-Haloketones. Tin enolates
readily react with aldehydes to give aldol-type products.16 On
the contrary, the substitution reaction with halides at the
halogenated carbon is unlikely to occur.17 In the reaction with
R-haloketone that has both carbonyl and halide moieties, a
carbonyl attack exclusively proceeds to afford halohydrin
derivatives.18 In fact, an uncatalyzed reaction of tin enolate 1a
with chloroketones 2a-c gave the halohydrin derivatives 4 in
high yields, not 1,4-diketones 3 (Table 1).
Ph
Ph
Ph
Ph
Ph
Ph
Ph
MgCl2
CuCl2
AlCl3
InCl3
ZnCl2
ZnBr2
ZnI2
Me
-(CH2)4-
ZnCl2
ZnCl2
10
2
a All reactions were carried out in THF (1 mL) with tin enolate 1a (2.0
mmol), chloroketone 2 (1.0 mmol), and catalyst (0.1 mmol) at 40 °C.
b Unidentified complicated mixture was produced in addition to the
formation of 3. c Starting material 2 was recovered in addition to the
formation of 3.
(9) (a) Miyano, M.; Dorn, C. R. J. Org. Chem. 1972, 37, 268-274. (b) Brown,
E.; Ragault, M. Tetrahedron Lett. 1973, 1927-1930. (c) Cuvigny, T.;
Larcheveque, M.; Normant, H. Tetrahedron Lett. 1974, 1237-1240. (d)
Stork, G.; Jung, M. E. J. Am. Chem. Soc. 1974, 96, 3682-3686. (e)
Miyashita, M.; Yanami, T.; Yoshikoshi, A. J. Am. Chem. Soc. 1976, 98,
4679-4681. (f) Jacobson, R. M.; Raths, R. A.; McDonald, J. H., III J.
Org. Chem. 1977, 42, 2545-2549. (g) Dauben, W. G.; Hart, D. J. J. Org.
Chem. 1977, 42, 3787-3793. (h) Sum, P. E.; Weiler, L. Can. J. Chem.
1978, 56, 2301-2304.
(10) (a) Corey, E. J.; Hegedus, L. S. J. Am. Chem. Soc. 1969, 91, 4926-4928.
(b) McMurry, J. E.; Melton, J. J. Am. Chem. Soc. 1971, 93, 5309-5311.
(c) Mukaiyama, T.; Narasaka, K.; Furusato, M. J. Am. Chem. Soc. 1972,
94, 8641-8642. (d) Katritzky, A. R.; Yang, Z.; Lam, J. N. J. Org. Chem.
1991, 56, 6917-6923. (e) Kubota, Y.; Nemoto, H.; Yamamoto, Y. J. Org.
Chem. 1991, 56, 7195-7196. (f) Katritzky, A. R.; Lang, H.; Wang, Z.;
Lie, Z. J. Org. Chem. 1996, 61, 7551-7557.
(11) (a) Baba, A.; Yasuda, M.; Yano, K.; Shibata, I.; Matsuda, H. J. Chem.
Soc., Perkin Trans. 1 1990, 3205-3207. (b) Yasuda, M.; Oh-hata, T.;
Shibata, I.; Baba, A.; Matsuda, H. J. Chem. Soc., Perkin Trans. 1 1993,
859-865. (c) Yasuda, M.; Katoh, Y.; Shibata, I.; Baba, A.; Matsuda, H.;
Sonoda, N. J. Org. Chem. 1994, 59, 4386-4392. (d) Yasuda, M.; Morimoto,
J.; Shibata, I.; Baba, A. Tetrahedron Lett. 1997, 38, 3265-3266.
(12) (a) Yasuda, M.; Hayashi, K.; Katoh, Y.; Shibata, I.; Baba, A. J. Am. Chem.
Soc. 1998, 120, 715-721. (b) Yasuda, M.; Chiba, K.; Baba, A. J. Am.
Chem. Soc. 2000, 122, 7549-7555.
We found an interesting effect of metal halides as a catalyst
on this type of reaction, and the results are summarized in Table
2. When a catalytic amount of LiCl was added to this reaction
system, a cross-coupling product, 1,4-diketone 3aa, was obtained
in 16% yield accompanied by an unidentified complicated
mixture, which was probably formed via carbonyl addition
(entry 1).19,20 MgCl2 and CuCl2 also gave the 1,4-diketone,
though the yields were low (entries 2 and 3). Moderate yields
were obtained by using AlCl3 or InCl3 (entries 4 and 5).
Gratifyingly, zinc halides (ZnCl2, ZnBr2, and ZnI2) completely
altered the reaction course to give the 1,4-diketone without any
other side products (entries 6-8). Only a 0.1 equiv of the
catalyst was effective for the cross-couplilng reaction. THF was
the best choice out of the solvents examined since toluene and
acetonitrile afforded 3aa in lower yields with ZnCl2 catalyst
(69% and 74%) compared with the >99% yield in entry 6. The
aliphatic and cyclic chloroketones 2b and 2c were also ap-
plicable for the ZnCl2-catalyzed system to give 1,4-diketones
3ab and 3ac, respectively (entries 9 and 10).
(13) For the Pd- or Ru-catalyzed coupling of R-bromoketone bearing bulky or
aryl substituents with tin enolate, see: Kosugi, M.; Takano, I.; Sakurai,
M.; Sano, H.; Migita, T. Chem. Lett. 1984, 1221-1224.
(14) For a recent example, see: Li, G. Y. Angew. Chem., Int. Ed. 2001, 40,
1513-1516 and references therein.
(15) A part of this work has been reported as a communication. Yasuda, M.;
Tsuji, S.; Shibata, I.; Baba, A. J. Org. Chem. 1997, 62, 8282-8283.
(16) (a) Noltes, J. G.; Creemers, H. M. J. C.; Van Der Kerk, G. J. M. J.
Organomet. Chem. 1968, 11, 21. (b) Labadie, S. S.; Stille, J. K. Tetrahedron
1984, 40, 2329-2336. (c) Yamamoto, Y.; Yatagi, H.; Maruyama, K. J.
Chem. Soc., Chem. Commun. 1981, 162.
We examined the generality of the zinc-catalyzed cross-
coupling reaction. Table 3 shows the effective and exclusive
(17) High temperature is required for halide coupling with tin enolates. Odic,
Y.; Pereyre, M. J. Organomet. Chem. 1973, 55, 273.
(18) (a) Yasuda, M.; Oh-hata, T.; Shibata, I.; Baba, A.; Matsuda, H.; Sonoda,
N. Tetrahedron Lett. 1994, 35, 8627-8630. (b) Yasuda, M.; Oh-hata, T.;
Shibata, I.; Baba, A.; Matsuda, H.; Sonoda, N. Bull. Chem. Soc. Jpn. 1995,
68, 1180-1186.
(19) Kosugi, M.; Takano, I.; Hoshino, I.; Migita, T. J. Chem. Soc., Chem.
Commun. 1983, 989-990.
(20) Padmanabhan, S.; Ogawa, T.; Suzuki, H. Bull. Chem. Soc. Jpn. 1989, 62,
2114-2116.
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A R T I C L E S
Yasuda et al.
Table 3. Reaction of Tin Enolate 1 with R-Haloketone 2 Catalyzed by Zinc Halidea
a All reactions were carried out in THF (2 mL) with tin enolate 1 (2.0 mmol), haloketone 2 (1.0 mmol), and zinc halide (0.1 mmol) at 40 °C. b The
reaction was carried out at 60 °C.
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Cross-Coupling Reaction of R-Chloroketones and Organotin Enolates
A R T I C L E S
Figure 2. 1H NMR spectra of the uncatalyzed reaction mixture of 1a with
2a in C6D6: (f) t ) 5 min, 25 °C; (g) t ) 30 min, 60 °C; and (h) t ) 60
min, 60 °C.
Scheme 2
Figure 1. 1H NMR spectra of the ZnCl2-catalyzed reaction mixture of 1a
with 2a in C6D6: (a) t ) 5 min, 25 °C; (b) t ) 15 min, 40 °C; (c) t ) 30
min, 60 °C; (d) t ) 60 min, 60 °C; and (e) t ) 90 min, 75 °C.
formation of 1,4-diketones 3 with various types of tin enolates
121,22 and R-haloketones 2. R-Bromoketones were also applied
to this reaction system to give 1,4-diketones in high yields
(entries 7 and 8). The efficient formation of 1,4-diketones from
cyclic haloketones was noteworthy (entries 5, 6, 8, 12, 16, and
20), because 2-bromocyclohexanone gave not 1,4-diketone but
an aldol-type product by our previous method with the highly
coordinated tin enolate.11b Even the reactions with sterically
hindered chloroketones 2g and 2h proceeded smoothly to give
1,4-diketones 3ag and 3ah in high yields (entries 10 and 11).
In entry 12, trans-4-tert-butyl-2-chlorocyclohexanone (2i) gave
a single isomer of cis-diketone 3ai, whose relative configuration
was unambiguously determined by X-ray analysis. High selec-
tivity was also observed in the reaction of 1b with 2i (entry
16). Interestingly, the cis-chloroketone 2j did not afford 1,4-
diketone but aldol product 4bj (entry 17). The use of ZnBr2
sometimes showed a higher yield than the use of ZnCl2 (entries
14 and 15). Tin enolates bearing electron-donating or -with-
drawing substituents 1e and 1f showed similar reactivity with
1a to form 1,4-diketones (entries 22 and 23).
Investigation of the Reaction Mechanism. To investigate
the reaction mechanism, the reaction mixture was monitored
by 1H NMR. Under the same conditions as in entry 6 in Table
2, the reaction proceeded too fast to allow observation. Slightly
different conditions with ZnCl2 (0.1 equiv), 1a (1.0 equiv), and
2a (1.0 equiv) in benzene-d6 gave an observable result as shown
in Figure 1. After 5 min at 25 °C, the signals corresponding to
aldol-type adduct 4aaSn, marked by asterisks in the chart,
appeared along with the starting chloroketone 2a (Figure 1a).
The increase of 1,4-diketone 3aa with the decrease of 4aaSn
can be seen in Figure 1b-e on gradually raising the temperature
from 25 to 75 °C for 90 min. In the uncatalyzed reaction as
shown in Figure 2, no signal corresponding to 4aaSn was
observed in 5 min at 25 °C in Figure 2f. On raising the
temperature to 60 °C, the slow formation of 4aaSn was observed
in Figure 2g and 2h. These results suggest that ZnCl2 accelerates
the precondensation of tin enolate with chloroketone and
catalyzes the rearrangement from carbonyl adduct 4aaSn to 3aa.
A plausible catalytic cycle can be shown in Scheme 2. At
first, tin enolate 1 adds to the R-chloroketone 2 at the carbonyl
carbon to form 5. The transmetalation of tin in 5 with zinc halide
gives the reactive intermediate zincate 6, which can readily
transform to the 1,4-diketone 3 by rearrangement of the oxoalkyl
group along with regeneration of zinc halide.23,24 Generation
of the zinc enolate by the transmetalation of 1 with zinc halide
is also likely to occur.25 The intermediate zincate 6 certainly
plays an important role in the rearrangement, which is prompted
by the affinity of zinc with halogen in 6.26
The carbonyl group in 2 acts as an important directing force
for coupling at the chloride site. The substitution step takes place
intramolecularly due to the precondensation at the carbonyl
group. In fact, no reactions were observed in the treatment of
1a with ethyl 2-chloroacetate or allyl chloride in the presence
of ZnCl2, which are typical reactive organic chlorides. As shown
in Scheme 3, even after completion of the uncatalyzed conden-
sation of 1a at the carbonyl group in 2a under the conditions
noted in entry 1 of Table 1, the addition of a catalytic amount
(23) (a) Nevar, N. M.; Kellin, A. V.; Kulinkovich, O. G. Synthesis 2000, 1259-
1262. (b) Kel’in, A. V.; Kulinkovich, O. G. Synthesis 1996, 330-332.
(24) We have recently reported the rearrangement of the aryl group from the
adduct which comes from R-haloketone with allylic tin(II) species. Yasuda,
M.; Tsuchida, M.; Baba, A. Chem. Commun. 1998, 563-564.
(25) A THF solution of an equiomolar mixture of 1a and ZnCl2 gave 91% of
Bu3SnCl at room temperature for 5 min. This result suggests fast
transmetalation between tin enolate and ZnCl2. In the reaction shown in
Scheme 2, however, only a catalytic amount of zinc halide is used and
most of the precondensation product comes from tin enolate.
(21) In general, tin enolates exist as an equilibrium mixture of keto- and/or enol-
type isomers whose ratio greatly depends on the substituents. In this paper,
all structures are shown as enol form for convenience.
(22) Pereyre, M.; Bellegarde, B.; Mendelsohn, J.; Valade, J. J. Organomet. Chem.
1968, 11, 97-110.
(26) Katritzky, A. R.; Xie, L.; Toader, D.; Serdyuk, L. J. Am. Chem. Soc. 1995,
117, 12015-12016.
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A R T I C L E S
Yasuda et al.
Scheme 3
Table 4. Effect of Additives in the Reaction of Tin Enolate 1a with
Allyl Bromide 7aa
entry
additive (mmol)
time/h
yield/%
1
2
3
4
5
6
7
8
9
ZnCl2 (0.1)
ZnCl2 (1)
ZnBr2 (1)
ZnI2 (1)
NiCl2 (1)
CuCl (0.1)
CuBr (0.1)
CuI (0.1)
24
24
24
24
20
16
16
16
20
20
0
0
0
0
10
>99
>99
>99
80
Scheme 4
CuCl2 (0.1)
CuBr2 (0.1)
10
>99
a All reactions were carried out in THF (1 mL) with tin enolate 1a (2.0
mmol), allyl bromide 7a (1.0 mmol), and additive at 40 °C.
place via equatorial attack to give E, which was hydrolyzed to
give 4bj. The formation of diketone is unlikely to occur because
the equilibrium between E and F largely lies on the side of E.
The equatorial attack of tin enolate to 2j is commonly observed;
both cases of uncatalyzed and Ph4SbBr-catalyzed reaction of
1b with 2j were reported to give E (M ) H) as a single isomer.18
The addition of ZnCl2 to the reaction mixture including only E
(M ) SnBu3) derived from uncatalyzed reaction of 1b with 2j
gave no 1,4-diketone and only chlorohydrin 4bj (M ) H) in
62% yield. Since the unsubstituted 2-halocyclohexanone system
has a low energy barrier between conformers, ZnCl2-catalyzed
reaction smoothly affords 1,4-diketone.28
Reaction of Tin Enolates with Allylic Halides. We next
turned our attention to the reaction with organic halides which
have no directing group such as the carbonyl moiety in
haloketones. As already mentioned above, no reactions were
observed in the ZnCl2-catalyzed reaction of 1a with allyl halides.
We have previously reported that >1 equiv of additive acceler-
ates the coupling of tin enolate with allylic halides.12 However,
the catalytic cross-coupling is still a problem to be solved.29
Table 4 shows the effect of catalysts in the reaction of 1a
with allyl bromide 7a. Even the use of 1 equiv of zinc halides
resulted in no reaction (entries 2-4). A catalytic amount of
NiCl2 gave a low yield of the coupling product 8aa (entry 5).
As shown in entries 6-10, copper halides effectively catalyzed
the reaction to give γ,δ-unsaturated ketone 8aa in high yields.
Copper halides could activate allylic halide to form a π-allylic
complex, or generate copper enolate by transmetalation with
tin enolate.30 When the copper-catalyzed reaction of 1a with
7a was monitored by NMR, only the starting materials and the
of ZnCl2 led to the transformation into 3aa in high yield (92%).
These results show the precondensation step should be included
in the reaction course.
It is noteworthy that each diastereomer of 4-tert-butyl-2-
chlorocyclohexanone (2i and 2j) showed contrastive results
(entries 16 and 17 in Table 3). These differences are clearly
ascribed to the conformation of intermediate carbonyl adducts.
For the formation of 1,4-diketone through the addition-
rearrangement mechanism, the intermediate should have an
oxoalkyl group and Cl in anti-periplanar positions such as B or
F in Scheme 4. Therefore, the reaction of 1b with 2i presumably
proceeds through B to diketone 3bi. The facial selective addition
of 1b to 2i via axial attack can be explained if the ZnCl2 catalyst
acts as does Ph4SbBr, which was previously reported to be the
catalyst for the selective formation of chlorohydrin B (M )
H).27 In fact, Ph4SbBr-catalyzed reaction of 1b with 2i in THF
for 24 h, in which B (M ) SnBu3) would be predominantly
formed in situ,18 followed by loading of a catalytic amount of
ZnCl2 gave exclusive formation of 3bi in 58% yield. On the
other hand, it is assumed that the reaction of 1b with 2j takes
(27) We have already reported the facial selectivity of the 2-chlorocyclohexanone
system with tin enolates (ref 18). The uncatalyzed reaction of 1b with 2i
gives both isomers B (M ) H) and C (M ) H) in 18% and 54% yields,
respectively, after workup. In the presence of a catalytic amount of Ph4SbBr,
the exclusive attack from the axial direction takes place to give B (M )
H) as a single product in 60% yield.
(28) 2-Chlorocyclohexanone exits as a mixture of conformers in comparable
ratios: Basso, E. A.; Kaiser, C.; Rittner, R.; Lambert, J. B. J. Org. Chem.
1993, 58, 7865-7869. The ZnCl2 reaction of tin enolate with either
conformer gives precondensation adduct bearing Cl and an oxoalkyl group
in the trans configuration as expected from the results in Scheme 4. We
reported that the Ph4SbBr-catalyzed reaction of tin enolates with 2-chloro-
cyclohexanone gave only the chlorohydrin with Cl and an oxoalkyl group
in trans positions (ref 18).
(29) Allylic tins were reported to couple with allylic bromides in the ZnCl2-
catalyzed reaction. Godschalx, J. P.; Stille, J. K. Tetrahedron Lett. 1983,
24, 1905-1908.
(30) Allred, G. D.; Liebeskind, L. S. J. Am. Chem. Soc. 1996, 118, 2748-
2749.
9
7444 J. AM. CHEM. SOC. VOL. 124, NO. 25, 2002

Cross-Coupling Reaction of R-Chloroketones and Organotin Enolates
A R T I C L E S
Table 5. Reaction of Tin Enolates 1 with Organic Halides 7
products at 63 °C (entry 3). Moderate yields were obtained in
the reaction with prenyl or benzyl bromide (entries 4 and 5).
When R-bromoester 7f was used as the substrate, the reaction
resulted in low conversion (entry 6).31 It is noteworthy that
allylic chlorides were also applied to the CuI-catalyzed reaction
system. The reaction with cinnamyl chloride 7g gave the
coupling products in 88% yield under THF reflux conditions,
while no reaction was observed without the catalyst (entries 7
and 8). Satisfactory yield was obtained in the reaction with crotyl
chloride 7h using DMF as a solvent.32 Other tin enolates were
also applied to the CuI-catalyzed coupling to give the cross-
coupling products in moderate to high yields (entries 12-15).
Catalyzed by CuIa
Conclusions
We have demonstrated the cross-coupling of carbonylmethyl
units using R-chloroketones and tin enolates as coupling
partners. Zinc halides showed excellent catalytic activity for
the coupling. The reaction course includes the precondensation
between tin enolates and R-haloketone providing an aldol-type
species and rearrangement of the oxoalkyl group with substitu-
tion of halogen to produce 1,4-diketones. The carbonyl group
in haloketone acts as a directing group for the coupling reaction.
NMR studies apparently suggest two steps are involved in the
reaction course. Zinc halides have two functions: (i) as a Lewis
acid accelerating and controlling the precondensation step
(formation of 5) and (ii) as an agent promoting the rearrange-
ment by releasing oxygen and bonding with halogen (formation
of 3 from 6). The reaction with organic halides which have no
directing group was catalyzed by a different type of catalyst.
The copper halides effectively catalyzed the cross-coupling of
tin enolates with allylic halides to give γ,δ-unsaturated ketones.
This system was also applied to chloride substrates as cationic
coupling partners.
Experimental Section
General. Melting points were taken on a Yanagimoto melting point
apparatus and are uncorrected. IR spectra were recorded as thin films
or as solids in KBr pellets on a Hitachi 260-30 spectrophotometer. 1H
and 13C NMR spectra were obtained with a JEOL JNM-GSX-270 (270
and 67.9 MHz) or a JEOL JNM-GSX-400 (400 and 100 MHz)
spectrometer, respectively, with TMS as internal standard. Mass spectra
were recorded on a JEOL JMS-DS303 or a Shimadzu GCMS-QP2000A
spectrometer. GLC analyses were performed on a Shimadzu GC-8A
with FID, using a 2 m × 3 mm column packed with SE-52. Flash
chromatography was performed on silica gel (Wakogel C-300). Bulb-
to-bulb distillation (Kugelrohr) was accomplished in a Sibata GTO-
250RS at the oven temperature and pressure indicated. Yields were
1
determined by GLC or H NMR with internal standards.
a All reactions were carried out in THF (1 mL) with tin enolate 1 (2.0
mmol), organic halide 7 (1.0 mmol), and CuI (0.1 mmol). b 8ae ) 1,3-
diphenyl-1-propanone. c 8af ) ethyl 4-oxo-4-phenylbutanoate. d Without
CuI. e DMF was used as solvent instead of THF.
Materials. THF was distilled from sodium and benzophenone. Tin
enolates 1a-d and 1g were prepared from tributyltin methoxide and
the corresponding enol acetates by known methods.16b,22 The tin enolates
1e and 1f were prepared from p-methoxy-R-acetoxystyrene33 and
p-chloro-R-acetoxystyrene33 with tributyltin methoxide in a similar
fashion.16b,22 All tin compounds were handled carefully because of their
toxicity. R-Haloketones 2a, 2b, 2c, 2d, 2f, and 2h were commercially
available. 2-Bromocyclohexanone (2e),34 2-chloropropiophenone (2g),35
and 4-tert-butylcyclohexanone (2i and 2j)36 were prepared according
product were observed without any intermediates. Evidence for
the generation of neither π-allylic copper nor copper enolate
was obtained even in the equimolar mixture of CuI and 7a or
CuI and 1a in THF. The reaction mechanism and the catalyst
behavior are not clear at this stage.
Table 5 shows the results of coupling between various types
of tin enolates 1 and organic halides 7 catalyzed by CuI. The
reaction of 1a with cinnamyl bromide 7b gave the cross-
coupling product quantitatively (entry 2). The reactions with
crotyl bromide 7c also proceeded smoothly and gave the
(31) The palladium-catalyzed coupling of haloester with tin enolate or allyltin
reagents was reported. Simpson, J. H.; Stille, J. K. J. Org. Chem. 1985,
50, 1759-1760.
(32) The reaction carried out in THF under the reflux condition resulted in low
yield (21%, 8ac:9ac; 64:36).
(33) Noyce, D. S.; Pollack, R. M. J. Am. Chem. Soc. 1969, 91, 119-124.
9
J. AM. CHEM. SOC. VOL. 124, NO. 25, 2002 7445

A R T I C L E S
Yasuda et al.
to the described methods. Allylic halides (and related halides) 7a-j
were commercial products. Zinc halides were dried under reduced
pressure before use.
data described in the literature. The spectral data of the product 3bb
was in excellent agreement with the commercially available sample
(Aldrich).
Uncatalyzed Reaction of Tin Enolates with Chloroketones. To a
solution of a tin enolate 1 (2.0 mmol) in dry THF (1 mL) was added
R-chloroketone 2 (1.0 mmol) under nitrogen. The mixture was stirred
under the reaction conditions noted in Table 1 and quenched with water
(5 mL). Diethyl ether (30 mL) and aqueous NH4F (15%; 15 mL) were
added and the homogeneous mixture was vigorously stirred for 20 min.
The resulting Bu3SnF was filtered off. The filtrate was washed with
water (30 mL × 2), dried (MgSO4), and evaporated. Flash chroma-
tography of the residue on silica gel gave pure products.
General Procedure for Synthesis of 1,4-Diketones (3). To a
mixture of a tin enolate 1 (2.0 mmol) and 0.1 mmol of zinc halide (or
other metal halides in Table 2) in dry THF (1 mL) was added
R-haloketone 2 (1.0 mmol) under nitrogen. The reaction mixture was
stirred under the reaction conditions noted in Table 2 or 3. Water (5
mL) was then added to the solution. Diethyl ether (30 mL) and aqueous
NH4F (15%; 15 mL) were added and the homogeneous mixture was
vigorously stirred for 20 min. The resulting Bu3SnF was filtered off.
The filtrate was washed with water (30 mL × 2), dried (MgSO4), and
evaporated. Flash chromatography of the resultant residue on silica gel
or recrystallization gave pure products.
Control Experiment for Investigation of Reaction Mechanism
(Scheme 3). To a solution of tin enolate 1a (2.0 mmol) in dry THF (1
mL) was added R-chloroketone 2a (1.0 mmol) under nitrogen. The
mixture was stirred at 40 °C for 6 h. Then ZnCl2 (0.1 mmol) was added
to the solution. The reaction mixture was stirred for 24 h and quenched
with water (5 mL). Diethyl ether (30 mL) and aqueous NH4F (15%;
15 mL) were added and the resulting Bu3SnF was filtered off. The
filtrate was washed with water (30 mL × 2), dried (MgSO4), and
evaporated to give an oil that was found by NMR and GLC analyses
to consist of the compound 3aa (92%) without 4aa.
1-(4-Methylphenyl)-4-phenylbutane-1,4-dione (3af). According to
the general procedure, this compound was prepared from 1a, ZnCl2,
and 2f in THF to give the product as a white solid after recrystallization
1
(hexane): mp 114-116 °C; IR (KBr) 1680 cm-1; H NMR (270 Hz,
CDCl3) δ 8.06-7.22 (m, 4H, aromatic), 7.58-7.44 (m, 3H, aromatic),
7.29-7.25 (m, 2H, aromatic), 3.45 (s, 4H, 2- and 3-H2), 2.42 (s, 3H,
Me); 13C NMR (67.9 Hz, CDCl3) 198.77 (s), 198.28 (s), 143.90 (s),
136.81 (s), 134.30 (s), 133.08 (d), 129.24 (d), 128.55 (d), 128.22 (d),
128.10 (d), 32.60 (t), 32.46 (t), 21.63 (q); MS (EI, 70 eV) m/z 252
(M+, 8), 119 (100), 105 (41); HRMS (EI, 70 eV) calcd for C17H16O2
252.1150, found m/z 252.1121, 252.1140, 252.1175 (M+). Anal. Calcd
for C17H16O2: C, 80.93; H, 6.39. Found: C, 80.63; H, 6.32.
2-Methyl-1,4-diphenylbutane-1,4-dione (3ag). According to the
general procedure, this compound was prepared from 1a, ZnCl2, and
2g in THF to give the product as a white solid after recrystallization
1
(hexane): mp 106 °C; IR (KBr) 2970 (alkyl), 1680, 1660 cm-1; H
NMR (270 Hz, CDCl3) 8.07-7.43 (m, 10H, aromatic), 4.23-4.15 (m,
1H, 2-H), 3.73 (dd, J ) 8.3, 17.6 Hz, 1H, 3-HA), 3.12 (dd, J ) 4.9,
17.6 Hz, 1H, 3-HB), 1.29 (d, J ) 7.3 Hz, 3H, Me); 13C NMR (67.9 Hz,
CDCl3) 203.33 (s, C-1), 198.41 (s, C-4), 136.64 (s), 133.14 (d), 136.06
(s), 132.92 (d), 128.62 (d), 128.52 (d), 128.48 (d), 128.05 (d), 42.30
(t, C-3), 36.23 (d, C-2), 17.91 (q, Me); MS (EI, 70 eV) m/z 252 (M+,
3.5), 147 (5), 105 (100), 77 (37), 51 (12); HRMS:(EI, 70 eV) calcd for
C17H16O2 252.1150, found m/z 252.1121, 252.1140, 252.1175 (M+).
Anal. Calcd for C17H16O2: C, 80.93; H, 6.39. Found: C, 80.63; H,
6.34.
(2R*,4S*)-4-tert-Butyl-2-(2-oxo-2-phenylethyl)cyclohexane-1-
one (3ai). According to the general procedure, this compound was
prepared from 1a, ZnCl2, and 2i in THF to give the product as a white
solid after recrystallization (hexane). The crystal obtained was suitable
for X-ray crystallographic analysis. Details of the crystal structure data
and analysis are provided in the Supporting Information: mp 133 °C;
NMR Study of the Reaction of 1a with 2a (Figure 1). To a dry
benzene-d6 solution of ZnCl2 (0.04 mmol) in an NMR tube was
1
1
IR (KBr) 2950, 1700, 1680 cm1; H NMR (400 MHz, CDCl3) 8.00-
introduced 1a (0.4 mmol) and 2a (0.4 mmol). H NMR spectra were
recorded at varying temperature from 25 to 75 °C as shown in Figure
1. Noncatalyzed reaction was carried out without ZnCl2 at 25-60 °C.
General Procedure for Synthesis of γ,δ-Unsaturated Ketones (8
and/or 9). To a mixture of tin enolate 1 (2.0 mmol) and a catalytic
amount of CuI (0.1 mmol) in dry THF (1 mL) was added organic halide
7 (1.0 mmol) under nitrogen. The reaction mixture was stirred under
the conditions noted in Table 5. Water (5 mL) was then added to the
solution. Diethyl ether (30 mL) and aqueous NH4F (15%; 15 mL) were
added and the resulting Bu3SnF was filtered off. The filtrate was washed
with water (30 mL × 2), dried (MgSO4), and evaporated. Flash
chromatography of the resultant residue on silica gel or recrystallization
gave pure products.
7.97 (m, 2H, aromatic), 7.57-7.53 (m, 1H, aromatic), 7.47-7.43 (m,
2H, aromatic), 3.62 (dd, J ) 17.58, 6.35 Hz, 1H, PhCOCHA), 3.21-
3.16 (m, 1H, 2-H), 2.69 (dd, J ) 17.58, 5.37 Hz, 1H, PhCOCHB),
2.47-2.43 (m, 2H), 2.21-2.13 (m, 2H), 1.74-1.67 (m, 1H), 1.54-
1.42 (m, 1H), 1.32-1.22 (m, 1H), 0.92 (s, 9H, CMe3); 13C NMR (100
MHz, CDCl3) 211.79 (s), 198.48 (s), 137.01 (s), 132.92 (d), 128.45,
(d), 128.00 (d), 46.94 (d), 45.48 (d), 41.16 (t), 38.44 (t), 35.19 (t),
32.36 (s), 28.61 (t), 27.58 (q); MS (EI, 70 eV) m/z 272 (M+, 18), 215
(35), 153 (64), 133 (18), 120 (33), 105 (100), 77 (27), 57 (22); HRMS
(EI, 70 eV) calcd for C18H24O2 272.1776, found m/z 272.1801,
272.1788, 272.1746 (M+). Anal. Calcd for C18H24O2: C, 79.37; H, 8.88.
Found: C, 79.49; H, 8.89.
(2R*,4S*)-4-tert-Butyl-2-(2-oxopropyl)cyclohexane-1-one (3bi).
According to the general procedure, this compound was prepared from
1b, ZnCl2, and 2i in THF to give the product as a colorless liquid after
flash chromatography (hexane/Et2O, 1/1) and distillation: bp 115 °C/1
mmHg; IR (KBr) 2950, 1710, 1700 cm1; 1H NMR (400 MHz, CDCl3)
3.05-2.93 (m, 2H), 2.42-2.35 (m, 2H), 2.21 (s, 3H, MeCdO), 2.20-
1.10 (m, ring), 0.90 (s, 9H, CMe3); 13C NMR (100 MHz, CDCl3) 211.79
(s), 207.28 (s), 46.94 (d), 45.59 (d), 43.31 (t), 41.07 (t), 34.93 (t), 32.35
(s, Me3C), 30.42 (q, MeCO), 28.53 (t), 27.58 (q, Me3C); MS (EI, 70
eV) m/z 167 (M+ - 43, 18), 153 (20), 111 (20), 57 (63), 43 (100).
Anal. Calcd for C13H22O2: C, 74.24; H, 10.54. Found: C, 70.49; H,
10.29.
Spectral Data. These products 3aa,11b 3ab,11b 3ac,11b 3ah,11b 3cb,11b
3cc,11c 3db,37 4bj,18b 8aa,12a 8ab,12a 8ac,38 9ac,39 8ad,40 9ad,41 8ae,12a
8af,11b 8da,42 8bb,12a 9bb,43 and 8ga44 were identified by the spectral
(34) Bedoukian, P. Z. J. Am. Chem. Soc. 1945, 67, 1430-1431.
(35) Olah, G. A.; Ohannesian, L.; Arvanaghi, M.; Parakash, G. K. S. J. Org.
Chem. 1984, 49, 2032-2034.
(36) Allinger, N. L.; Allinger, J.; Freiberg, L. A.; Czaja, R. F.; Lebel, N. A. J.
Am. Chem. Soc. 1960, 82, 5876-5882.
(37) Tsuda, T.; Satomi, H.; Hayashi, T.; Saegusa, T. J. Org. Chem. 1987, 52,
439-443.
(38) Tanko, J. M.; Drumright, R. E.; Suleman, N. K.; Brammer, L. E., Jr. J.
Am. Chem. Soc. 1994, 116, 1785-1791. Roberts, R. M.; Landolt, R. G.;
Greene, R. N.; Heyer, E. W. J. Am. Chem. Soc. 1967, 89, 1404-1411.
(39) Roberts, R. M.; Landolt, R. G.; Greene, R. N.; Heyer, E. W. J. Am. Chem.
Soc. 1967, 89, 1404-1411.
(40) Michael, J. P.; Nkwelo, M. M. Tetrahedron 1990, 46, 2549-2560.
(41) Jemison, R. W.; Laird, T.; Ollis, W. D.; Sutherland, I. O. J. Chem. Soc.,
Perkin Trans. 1 1980, 1450-1457.
5,5-Dimethyl-1-phenylhexane-1,4-dione (3ca). According to the
general procedure, this compound was prepared from 1c, ZnCl2, and
2a in THF to give the product as a colorless liquid after flash
chromatography (hexane/Et2O, 10/1) and distillation: bp 125 °C/1
mmHg; IR (neat) 1680, 1660 cm-1; 1H NMR (400 Hz, CDCl3) 7.99-
7.46 (m, 5H, aromatic), 3.26 (t, J ) 6.4 Hz, 2H, 2-H2), 2.97 (t, J ) 6.4
(42) Molandar, G. A.; Kimberly, O. C. J. Org. Chem. 1993, 58, 5931-5943.
(43) Maruoka, K.; Banno, H.; Yamamoto, H. Tetrahedron: Asymmetry 1991,
2, 647-662.
(44) Barentsen, H. M.; Sieval, A. B.; Cornelisse, J. Tetrahedron 1995, 51, 7495-
7520.
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7446 J. AM. CHEM. SOC. VOL. 124, NO. 25, 2002

Cross-Coupling Reaction of R-Chloroketones and Organotin Enolates
A R T I C L E S
Hz, 2H, 3-H2), 1.22 (s, 9H, But); 13C NMR (100 Hz, CDCl3) 214.66
(C-4), 198.96 (C-1), 136.88, 133.05, 128.56, 128.06, 44.07, 32.42,
30.77, 26.64 (5-Me3); MS (CI, 70 eV) m/z 219 (M+ + 1, 100), 161
(57), 133 (13), 105 (16); HRMS (CI, 70 eV) calcd for C12H20O2
219.3037, found m/z 219.1370, 219.1394, 219.1376 (M+ + 1). Anal.
Calcd for C14H18O2: C, 77.03; H, 8.31. Found: C, 76.98; H, 8.38.
1-(4-Methoxyphenyl)-4-phenylbutane-1,4-dione (3ea) According
to the general procedure, this compound was prepared from 1e, ZnCl2,
and 2a in THF to give the product as a yellow solid after recrystalli-
zation (hexane/benzene, 3/1): mp 98-100 °C; IR (KBr) 1692, 1673
cm-1; 1H NMR (400 MHz, CDCl3) 8.05-8.00 (m, 4H, aromatic), 7.57-
7.46 (m, 3H, aromatic), 6.96-6.93 (m, 2H, aromatic), 3.88 (s, 3H, Me),
3.47-3.39 (m, 4H, 2-H2 and 3-H2); 13C NMR (100 MHz, CDCl3)
198.85, 197.14, 163.50 (C-OMe), 136.81, 133.06, 130.35, 129.87,
128.55, 128.09, 113.70, 55.43 (Me), 32.63, 32.19; MS (EI, 70 eV) m/z
268 (M+, 40), 135 (100), 105 (20), 77 (16); HRMS (EI, 70 eV) calcd
for C17H16O3 268.1099, found m/z 268.1084, 268.1108, 268.1107 (M+).
Anal. Calcd for C17H16O3: C, 76.10; H, 6.01. Found: C, 76.38; H,
6.19.
1-(4-Chlorophenyl)-4-phenylbutane-1,4-dione (3fa). According to
the general procedure, this compound was prepared from 1f, ZnCl2,
and 2a in THF to give the product as a white solid after recrystallization
(hexane/benzene, 3/1): mp 114 °C; IR (KBr) 1670, 1660 cm1; 1H NMR
(400 MHz, CDCl3) 8.05-7.96 (m, 4H, aromatic), 7.60-7.56 (m, 1H,
aromatic), 7.50-7.44 (m, 4H, aromatic), 3.49-3.40 (m, 4H, 2-H2 and
3-H2); 13C NMR (100 MHz, CDCl3) 198.48, 197.47, 139.57, 136.65,
135.11, 133.22, 129.53, 128.91, 128.61, 128.10, 32.53, 32.49; MS (EI,
70 eV) m/z 272 (M+, 53), 139 (59), 133 (13), 111 (13), 105 (100), 77
(23); HRMS (EI, 70 eV) calcd for C16H13O2Cl 272.0604, found m/z
272.0603, 272.0633, 272.0604 (M+). Anal. Calcd for C16H13O2Cl: C,
70.46; H, 4.80; Cl, 13.00. Found: C, 70.25; H, 4.82; Cl, 13.28.
1,3-Diphenyl-4-pentene-1-one (9ab). According to the general
procedure, this compound was prepared from 1a, CuI, and 7b in THF.
The title compound was obtained with 8ab and separated by flash
chromatography (hexane/Et2O, 20/1) and distillation: bp 152 °C/1
mmHg; IR (KBr) 3090, 1700, 1620 cm1; 1H NMR (270 MHz, CDCl3)
7.94-7.90 (m, 2H, aromatic), 7.57-7.17 (m, 8H, aromatic), 6.11-
5.98 (m, 1H, 4-H), 5.07 (d, J ) 6.84 Hz, 1H, CHdCHH1), 5.08-4.99
(m, 2H, 5-H2), 4.18-4.10 (m, 1H, 3-H), 3.44 (dd, J ) 16.6, 7.8 Hz,
1H, 2-HA), 3.35 (dd, J ) 16.6, 6.8 Hz, 1H, 2-HB); 13C NMR (67.9
MHz, CDCl3) 197.99, (s, C-1), 142.99 (s), 140.57 (d, C-4) 136.97 (s),
132.85 (d), 128.42 (d), 127.90 (d), 127.58 (d), 126.39 (d), 114.54 (t,
C-5), 44.36 (d, C-3), 43.83 (t, C-2); MS (EI, 70 eV) m/z 236 (M+, 9),
117 (12), 105 (100), 77 (21); HRMS (EI, 70 eV) calcd for C17H16O
236.1201, found m/z 236.1189, 236.1195, 236.1196 (M+). Anal. Calcd
for C17H16O: C, 86.40; H, 6.82. Found: C, 86.35; H, 6.87.
Acknowledgment. This work was supported by a Grant-in-
Aid for Scientific Research, the Ministry of Education, Science,
Sports, and Culture, of the Japanese Government. Thanks are
due to Mrs. Y. Miyaji and Mr. H. Moriguchi, Faculty of
Engineering, Osaka University, for assistance in obtaining NMR
and MS spectra.
Supporting Information Available: Experimental details and
tables for X-ray crystal structures of 3ai (PDF and CIF). This
material is available free of charge via the Internet at
http://pubs.acs.org.
JA0258172
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J. AM. CHEM. SOC. VOL. 124, NO. 25, 2002 7447