Nickel-catalyzed arylative ring-opening of 3-methylenecycloalkane-1,1- dicarboxylates

Article abstract of DOI:10.1021/ol100599c

An arylative ring-opening reaction of cyclic allylmalonates with arylzinc reagents under nickel catalysis has been developed. Upon the ring-opening sp³C-sp³C bond cleavage, the allylic moiety serves as an allylic electrophile to reac

Full text of DOI:10.1021/ol100599c

ORGANIC
LETTERS
2010
Vol. 12, No. 10
2254-2257
Nickel-Catalyzed Arylative Ring-Opening of
3-Methylenecycloalkane-1,1-dicarboxylates
Yuto Sumida,† Hideki Yorimitsu,*,‡ and Koichiro Oshima*,†
Department of Material Chemistry, Graduate School of Engineering, Kyoto UniVersity,
Kyoto-daigaku Katsura, Nishikyo-ku, Kyoto 615-8510, Japan, and Department of
Chemistry, Graduate School of Science, Kyoto UniVersity,
Sakyo-ku, Kyoto 606-8502, Japan
yori@kuchem.kyoto-u.ac.jp; oshima@orgrxn.mbox.media.kyoto-u.ac.jp
Received March 12, 2010
ABSTRACT
An arylative ring-opening reaction of cyclic allylmalonates with arylzinc reagents under nickel catalysis has been developed. Upon the ring-
opening sp3C-sp3C bond cleavage, the allylic moiety serves as an allylic electrophile to react with arylzinc reagents. Simultaneously, the
malonate moiety is converted to the corresponding zinc enolate, which can react further with electrophiles. The overall process increases
molecular complexity and diversity starting from readily available substrates and is useful in organic synthesis.
Development of efficient methods for cleavage of C-C
bonds catalyzed by transition-metal complexes is a new trend
and a challenging topic of modern organic chemistry.1,2
Having been long pursued, cleavage of unstrained sp3C-sp3C
bonds is still difficult owing to their stability as well as the
high directionality of the σ-orbital of sp3C-sp3C bonds.
Several noteworthy examples of cleavage of unstrained
sp3C-sp3C bonds under transition-metal catalysis have been
reported. Among them, ꢀ-carbon elimination3 and retro-
allylation1g,4 from metal alkoxides have been well exploited.
Another talented approach to cleave sp3C-sp3C bonds
utilizes highly stabilized carbanions including ꢀ-dicarbonyl
enolates5 and cyclopentadienyl anions6 as leaving groups.
Transition-metal-catalyzed synproportionation5a,b of allyl-
malonate derivatives is useful because of the importance of
malonate chemistry in organic synthesis. Recently, Kotora
described nickel-catalyzed deallylation of allylmalonates
under mild conditions with organometallic reagents.5c-f
Nevertheless, the allylic moieties of the malonate derivatives
are simply cleaved off5c-f or transferred to another malonate
anion5a,b without increasing molecular complexity and
diversity. Herein, we report nickel-catalyzed arylative ring-
opening of cyclic allylmalonate derivatives with arylzinc
reagents. The new transformation increases molecular com-
plexity and diversity starting from readily available precur-
† Department of Material Chemistry.
‡ Department of Chemistry.
(1) (a) Jun, C.-H. Chem. Soc. ReV. 2004, 33, 610–618. (b) Murakami,
M.; Makino, M.; Ashida, S.; Matsuda, T. Bull. Chem. Soc. Jpn. 2006, 79,
1315–1321. (c) Satoh, T.; Miura, M. J. Synth. Org. Chem. Jpn. 2006, 64,
1199–1207. (d) Kondo, T.; Mitsudo, T. Chem. Lett. 2005, 34, 1462–1467.
(e) Nakao, Y.; Hiyama, T. J. Synth. Org. Chem. Jpn. 2007, 65, 999–1008.
(f) Necˇas, D.; Kotora, M. Curr. Org. Chem. 2007, 11, 1566–1591. (g)
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Watanabe, Y.; Mitsudo, T. J. Am. Chem. Soc. 1998, 120, 5587–5588. (b)
Hayashi, S.; Hirano, K.; Yorimitsu, H.; Oshima, K. J. Am. Chem. Soc. 2006,
128, 2210–2211. (c) Takada, Y.; Hayashi, S.; Hirano, K.; Yorimitsu, H.;
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5048–5049. (h) Sumida, Y.; Hayashi, S.; Hirano, K.; Yorimitsu, H.; Oshima,
K. Org. Lett. 2008, 10, 1629–1632. (i) Imoto, J.; Hayashi, S.; Hirano, K.;
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10.1021/ol100599c  2010 American Chemical Society
Published on Web 04/15/2010

sors and allows us to regard a ꢀ-dicarbonyl moiety as a
leaving or protective group, utilizing the allylic moieties as
allylic electrophiles.
Treatment of diethyl 4-methyl-3-methylenecyclopentane-
1,1-dicarboxylate (1a) with 2 equiv of phenylzinc bromide,
which was prepared from zinc bromide and phenyl Grignard
reagent in THF, in the presence of 5 mol % of Ni(cod)2/
2PPh3 in toluene at room temperature afforded the corre-
sponding product 2a in 75% yield, and a part of 1a still
remained (Table 1, entry 1). The reaction was completed at
zerovalent nickel complex (entries 5 and 6). Other transition-
metal catalysts were also examined. The product was obtained
in low yield when di- or zerovalent palladium complex was
used as a catalyst (entries 7 and 8). A cobalt complex failed to
catalyze the ring-opening reaction (entry 9).
Various methylenecycloalkanes and arylzinc reagents were
subjected to the optimized conditions (Table 1, entries 2 and
5), and the results are summarized in Table 2. The reactions
Table 2. Scope of Methylenecycloalkanes and Organozinc
Reagents
Table 1. Optimization of Reaction Conditions
entry
catalyst
PhZnX
additive
yielda/%
1
2
3
4
5
6
7
8
9
Ni(cod)2/2PPh3
Ni(cod)2/2PPh3
Ni(cod)2/2PPh3
Ni(cod)2/2PPh3
NiBr2(PPh3)2
Ni(acac)2/2PPh3
PdCl2(PPh3)2
Pd(PPh3)4
PhZnBrb
none
none
none
MgBr2
MgBr2
MgBr2
MgBr2
MgBr2
MgBr2
75c,d
96
PhZnBrb
PhZnI·LiCl
PhZnI·LiCl
PhZnI·LiCl
PhZnI·LiCl
PhZnI·LiCl
PhZnI·LiCl
PhZnI·LiCl
11d
90
89
89
12d
26d
0d
CoCl2(PPh3)2
a Isolated yields. b Prepared from PhMgBr and ZnBr2. The ring-opening
reaction was performed for 8 h. c At room temperature. d NMR yields.
60 °C and gave 2a in excellent yield (entry 2). Knochel’s
arylzinc iodide·lithium chloride complex7 is easy to prepare
from zinc powder and the corresponding aryl iodide in the
presence of lithium chloride in THF, displaying an excep-
tionally broad range of functionalized zinc reagents. Hence,
we applied the phenylzinc iodide·lithium chloride complex
to the reaction. Disappointingly, product 2a was obtained in
only 11% yield (entry 3). However, an addition of magne-
sium bromide, which should be furnished in situ in the case
of phenylzinc bromide in entries 1 and 2, dramatically
increased the yield of the product up to 90% (entry 4). We
assume that magnesium bromide promotes the sp3C-sp3C
bond cleavage by working as a Lewis acid to activate
dicarboxylate moiety (vide infra).8 Alternatively, it might
promote transmetalation between nickel and organozinc
complexes.9 Divalent nickel complexes, such as NiBr2(PPh3)2
and Ni(acac)2/2PPh3, were effective as well as the expensive
a PhZnBr and 2-MeC6H4ZnBr were prepared from the corresponding
ArMgBr and ZnBr2. No additional MgBr2 needed. The ring-opening reaction
was performed for 8 h. b Isolated yields. c The reaction was performed with
2-MeC6H4ZnI·LiCl for 30 h. d Prepared from C6H5CH2Br with Zn powder.
e NMR yield. f At room temperature.
(5) (a) Nilsson, Y. I. M.; Andersson, P. G.; Ba¨ckvall, J.-E. J. Am. Chem.
Soc. 1993, 115, 6609–6613. (b) Bricout, H.; Carpentier, J.-F.; Mortreux,
A. Tetrahedron Lett. 1997, 38, 1053–1056. (c) Necˇas, D.; Tursky´, M.;
Kotora, M. J. Am. Chem. Soc. 2004, 126, 10222–10223. (d) Necˇas, D.;
Tursky´, M.; Tisˇlerova, I.; Kotora, M. New J. Chem. 2006, 30, 671–674. (e)
Necˇas, D.; Tursky´, M.; Drabina, P.; Sedla´k, M.; Kotora, M. Organometallics
2006, 25, 901–907. (f) Necˇas, D.; Kotora, M. Org. Lett. 2008, 10, 5261–
5263. (g) Wilsily, A.; Nguyen, Y.; Fillion, E. J. Am. Chem. Soc. 2009,
131, 15606–15607.
of methylenecyclopentane 1a with 4-methylphenyl- and
4-methoxyphenylzinc reagents proceeded to afford the cor-
responding products in high yields (entries 1 and 2).
Although the efficiency of the reaction with sterically
hindered 2-methylphenylzinc iodide·lithium chloride was
moderate, a high yield was obtained when 2-methylphenylz-
inc bromide was used (entry 3). The reactions of 1a with
(6) Fisher, E. L.; Lambert, T. H. Org. Lett. 2009, 11, 4108–4110.
(7) Krasovskiy, A.; Malakhov, V.; Gavryushin, A.; Knochel, P. Angew.
Chem., Int. Ed. 2006, 45, 6040–6044.
Org. Lett., Vol. 12, No. 10, 2010
2255

electron-deficient 4-fluorophenyl- and 4-ethoxycarbonylphe-
nylzinc reagents provided the ring-opening arylated products
in 90% and 59% yields, respectively (entries 4 and 5). An
alkenylzinc reagent could be employed to give the desired
product in 66% yield (entry 6). An attempt to perform the
alkylative ring-opening with benzylzinc bromide resulted in
the formation of the desired product in only 28% NMR yield
(entry 7). Methylenecyclohexane 1b underwent the arylative
ring-opening smoothly to form 2i in excellent yield (entry
8). Methylenecyclopentane 1c having a ꢀ-ketoester part
participated in the reaction with high efficiency at room
temperature (entry 9). Cyclic 1,3-diester 1d, which is readily
available from Meldrum’s acid,10 was also more reactive than
acyclic 1,3-diester substrates and easily transformed into 2k
at room temperature (entry 10). Moreover, not only diester
and ketoester but also cyclic diamide 1e was applicable and
converted to arylative ring-opening product 2l in 92% yield
(entry 11). Unfortunately, no reaction took place when
monoester 1f or monoketone 1g was used (entries 12 and
13). Thus, the dicarbonyl moieties proved to be essential for
the success of the reaction.
Table 3. Scope of Allylmalonate Derivatives
a Isolated yields. b 4c/4d ) 48/52. E/Z of 4d ) 71/29.
prenylation of 2-naphthylzinc bromide with 3f failed due to
its steric hindrance (entry 4).
On the basis of these facts, we propose the following
reaction mechanism as shown in Scheme 2. Dicarbonyl
We next investigated the reaction of acyclic substrates with
an arylzinc reagent under nickel catalysis. The catalytic
system is also effective for the reaction of diethyl allyl-
(methyl)malonate (3a) with 2-naphthylzinc bromide to yield
2-allylnaphthalene (4a) and diethyl methylmalonate (5a) as
a byproduct (Scheme 1). This result encouraged us to
Scheme 2. Proposed Reaction Mechanism
Scheme 1
.
Reaction of Allylmethylmalonate with 2-NpZnBr
(2-Np ) 2-Naphthyl)
compound 1a coordinates to magnesium bromide. The
coordination assists the oxidative addition to zerovalent
nickel under cleavage of the sp3C-sp3C bond to form nickel
complex 6. Transmetalation between 6 and phenylzinc
reagent followed by reductive elimination11 gives zinc
enolate 712 and regenerates the starting nickel complex.
Finally, protonolysis of the resulting zinc enolate 7 would
provide 2a.
Intermediate 7 could be trapped with various electrophiles.
Treatment of the reaction mixture containing 7 with
CD3CO2D gave 8a (Table 4, entry 1). Furthermore, alkylation
of zinc enolate 7, the reactivity of which has been relatively
unknown, with the reactive organic halides provided the
corresponding products 8b-e in good to excellent yields
(entries 2-5).
examine the scope of various acyclic allylmalonate deriva-
tives in the reaction, which is summarized in Table 3.
On treatment of 3b bearing a methallyl group with
2-naphthylzinc bromide, a high yield of 2-methallylnaph-
thalene (4b) was obtained (Table 3, entry 1). Although the
reaction of crotyl-substituted 3c proceeded successfully, the
products were obtained as a mixture of regio- and stereoi-
somers (entry 2). The lack of regio- and stereoselectivity
indicates that the reaction pathway involves a π-allylnickel
complex. Meanwhile, 4e was obtained in quantitative yield
as the sole product in the case of 3e (entry 3). Attempted
A sequence of arylative ring-opening of 1b, trapping with
allyl bromide, and ring-closing metathesis13 of 9 enabled formal
(8) Magnesium activates dicarbonyl compounds: (a) Yang, D.; Gao, Q.;
Lee, C.-S.; Cheung, K.-K. Org. Lett. 2002, 4, 3271–3274. (b) Yang, D.;
Li, J.-H.; Gao, Q.; Yan, Y.-L. Org. Lett. 2003, 5, 2869–2871. (c) Yip, K.-
T.; Li, J.-H.; Lee, O.-Y.; Yang, D. Org. Lett. 2005, 7, 5717–5719. (d) Coscia,
R. W.; Lambert, T. H. J. Am. Chem. Soc. 2009, 131, 2496–2498.
(9) Effect of magnesium salts on arylzinc reagents under nickel catalysis:
Jin, L.; Liu, C.; Liu, J.; Hu, F.; Lan, Y.; Batsanov, A. S.; Howard, J. A. K.;
Marder, T. B.; Lei, A. J. Am. Chem. Soc. 2009, 131, 16656–16657.
(10) Yamamoto, Y.; Nakagai, Y.-I.; Ohkoshi, N.; Itoh, K. J. Am. Chem.
Soc. 2001, 123, 6372–6380.
(11) (a) Hayashi, T.; Yamamoto, A.; Hagihara, T. J. Org. Chem. 1986,
51, 723–727. (b) Evans, P. A.; Uraguchi, D. J. Am. Chem. Soc. 2003, 125,
7158–7159.
(12) Formation of zinc enolate via sp3C-sp3C bond cleavage: Sada, M.;
Matsubara, S. J. Am. Chem. Soc. 2010, 132, 432–433.
(13) Sholl, M.; Trnka, T. M.; Morgan, J. P.; Grubbs, R. H. Tetrahedron
Lett. 1999, 40, 2247–2250.
2256
Org. Lett., Vol. 12, No. 10, 2010

Table 4. Reaction of Electrophile with Zinc Enolate 7
Scheme 3. Arylative Ring Expansion (E ) CO2Et)
involves nickel-mediated ring-opening sp3C-sp3C bond
cleavage, arylation of the allylic moiety, and the formation
of the corresponding zinc enolate which is ready for further
functionalization.
Acknowledgment. This work was supported by Grants-
in-Aid for Scientific Research and Global COE Research
Programs from JSPS. Y.S. acknowledges JSPS for financial
support.
a Isolated yields. b 87% D.
arylative ring expansion of 1b into cycloheptene 10, which one
can hardly accomplish by a different way (Scheme 3).
In summary, we have developed a nickel-catalyzed ary-
lative ring-opening reaction of 3-methylenecycloalkane-1,1-
dicarboxylate derivatives with arylzinc reagents. The reaction
Supporting Information Available: Characterization data
of the products. This material is available free of charge via
the Internet at http://pubs.acs.org.
OL100599C
Org. Lett., Vol. 12, No. 10, 2010
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