Nickel-catalyzed [3 + 2] cycloaddition of α,β-unsaturated ketones with vinyl oxiranes

Article abstract of DOI:10.1246/cl.2011.808

A nickel-catalyzed cycloaddition of α,β-unsaturated ketones with vinyl oxiranes to afford polysubstituted tetrahydrofurans has been developed. The key intermediate is a five-membered nickelacycle, which is formed by oxidative cyclization of nickel(0) to α

Full text of DOI:10.1246/cl.2011.808

doi:10.1246/cl.2011.808
808
Published on the web June 25, 2011
Nickel-catalyzed [3 + 2] Cycloaddition of ¡,¢-Unsaturated Ketones with Vinyl Oxiranes
Saori Sako, Takuya Kurahashi,* and Seijiro Matsubara*
Department of Material Chemistry, Graduate School of Engineering, Kyoto University, Kyoto 615-8510
(Received May 20, 2011; CL-110430; E-mail: tkuraha@orgrxn.mbox.media.kyoto-u.ac.jp,
matsubar@orgrxn.mbox.media.kyoto-u.ac.jp)
Me
EtO
O
A nickel-catalyzed cycloaddition of ¡,¢-unsaturated ketones
1a
with vinyl oxiranes to afford polysubstituted tetrahydrofurans
has been developed. The key intermediate is a five-membered
nickelacycle, which is formed by oxidative cyclization of
nickel(0) to ¡,¢-unsaturated ketones.
O
O
+
Ph
O
Me
O
Me
EtO
N
2a (2.5 equiv)
O
[Ni(cod)2]
(1.0 equiv)
Ni
OEt
Ph
Toluene
r.t., 15 min
Toluene
100 °C, 24 h
P
O
Ph2
+
Ph
O
Cy
4 99% yield
3aa 65% yield
Transition-metal-catalyzed cycloadditions represent a pow-
erful strategy of assembling complex heterocyclic compounds
from readily available starting materials. Thus, the development
of new formal reaction patterns still constitutes an important
ongoing challenge.1 Among these, a formal [3 + 2] cyclo-
addition of oxiranes with olefins seems to be an attractive
strategy to construct tetrahydrofuran frameworks in a single
operation. However, these types of cycloaddition are rarely
reported.2 We recently developed a series of nickel-catalyzed
cycloaddition using ¡-ester-substituted ¡,¢-unsaturated ketones
as a key component.3 During the course of our study, we found
that ¡-ester-substituted ¡,¢-unsaturated ketones 1 reacted with
vinyl oxiranes 2 to furnish polysubstituted tetrahydrofuran 3 via
a formal [3 + 2] cycloaddition; the reaction process included
oxidative cyclization of ¡-ester-substituted ¡,¢-unsaturated
ketones to nickel(0).
N
PPh2
IP-a (1.0 equiv)
Me
Me
O
EtO
EtO
O
Me
O
O
Ph
O
Ph
Ph
1b
1c
1d
Scheme 1. Stoichiometric reaction.
Table 1. [3 + 2] Cycloaddition of ¡,¢-unsaturated ketone 1a
with vinyl oxirane 2a with nickel catalysta
O
Me
Me
EtO
O
O
[Ni(cod)2] (10 mol %)
Ligand (20 mol %)
O
+
OEt
Ph
Toluene, 24 h
O
O
Ph
1a
2a
3aa
Ph
tBu
Ph
We first examined the stoichiometric reaction. The reaction
of ¡-ester-substituted ¡,¢-unsaturated ketone 1a was treated
with [Ni(cod)2] and iminophosphine ligand4 IP-a in toluene at
ambient temperature for 15 min (Scheme 1). Oxa-nickelacycle
4 was obtained in quantitative yield.3,5 Neither benzylidene-
substituted pentane-2,4-dione 1b, diethyl malonate 1c, nor enone
1d participated in oxidative cyclization with [Ni(cod)2]/IP-a,
and each was recovered unchanged quantitatively. Treatment of
4 with vinyl oxirane (2a) in toluene at 100 °C for 24 h afforded
tetrahydrofuran 3aa in 65% yield. The results prompted us to
investigate the possibilities of the catalytic reactions of 1a with
2a. Indeed, the reaction of 1a with 2a in the presence of
10 mol % of [Ni(cod)2] and 20 mol % of IP-a in toluene at
100 °C for 24 h furnished the tetrahydrofuran 3aa in 56% yield
(Table 1, Entry 1). Not even trace amounts of cycloadduct 3aa
were obtained in the absence of nickel. Further examination of
reaction conditions revealed that the cycloaddition proceeds at
lower reaction temperature (60 °C), providing a higher yield of
desired cycloadduct 3aa (75% yield, Entry 2). It was also found
that the reaction furnished 3aa in 98% yield at 30 °C (Entry 3).
In other reaction media, the yields of 3aa were decreased
(Entries 4-6). Among the iminophosphines examined, cyclo-
hexylamine-derived ligand IP-a gave the best result (Entries 3
and 7-9). With other phosphine ligands, such as PMe3, PMe2Ph,
and PPh3, the reaction afforded even lower amounts of desired
cycloadduct 3aa (Entries 10-12).
N
N
N
PPh2
IP-b
PPh2
PPh2
IP-d
IP-c
Entry Ligand
Solvent
Temperature/°C Yield/%b
1
2
3
4
5
6
7
8
9
IP-a
IP-a
IP-a
IP-a
IP-a
IP-a
IP-b
IP-c
IP-d
PMe3
Toluene
Toluene
Toluene
THF
100
60
30
30
30
30
30
30
30
30
30
30
56
75
98
77
37
18
34
11
59
<1
<1
9
MeCN
Pyridine
Toluene
Toluene
Toluene
Toluene
10
11
12
PMe2Ph Toluene
PPh3 Toluene
aReactions were carried out using [Ni(cod)2] (10 mol %),
ligand (20 mol %), 1a (0.5 mmol), and 2 (1.25 mmol) for
24 h. bReactions afford tetrahydrofurans 3 as a mixture of
inseparable diastereoisomers.
that vinyl oxirane 2b possessing pentyl substituent on the
oxirane ring also reacted with ¡,¢-unsaturated ketone 1a to
furnish the corresponding tetrahydrofuran derivative 3ab in 71%
yield (Entry 2). However, the reaction of 1a with vinyl oxirane
2c possessing gem-dimethyl substituents on the oxirane ring did
The scope of ¡,¢-unsaturated ketones 1 and vinyl oxiranes
2 in the cycloaddition is summarized in Table 2. It was found
Chem. Lett. 2011, 40, 808-809
© 2011 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/

809
Table 2. Nickel-catalyzed [3 + 2] cycloaddition of ¡,¢-un-
O
OEt
O
O
saturated ketones 1 with vinyl oxiranes 2a
Me
Ph
CO2Et
O
R1
Me
Ph
N
R1
O
O
[Ni(cod)2] (10 mol %)
Ni(0)
O
O
IP-a (20 mol %)
R3
P
3aa
1a
+
EtO
R4
R3
Ph2
OEt
R2
Toluene, 30 °C, 24 h
R4
O
O
R2
O
1
2
3
Me
EtO
Me
O
Me
EtO
O
Me
EtO
O
Me
OEt
EtO
O
Me
EtO
Ph
N
O
O
Ph
O
O
O
O
Ni
1a
1e
1f
1g
Ni
P
Ph2
O
Ph
4
O
OMe
O
CF3
O
5
O
Me
EtO
Ph
EtO
2a
O
Pr
O
Ph
1h
1i
R4
Scheme 2. Plausible reaction mechanism.
Entry
1
2
R3
3
Yield/%b
This work was supported by Grants-in-Aid from the
Ministry of Education, Culture, Sports, Science and Technology,
Japan. T.K. also acknowledges the Asahi Glass Foundation,
Kansai Research Foundation, and Toyota Physical and Chemical
Research Institute.
1
2
3
4
5
6
7
8
1a
2a
2b
2c
2a
2a
2a
2a
2a
H
H
H
Me
H
H
H
3aa
3ab
3ac
3ea
3fa
3ga
3ha
3ia
98
71
<1
81
76
63
71
51
1a
1a
1e
1f
1g
1h
1i
C5H11
Me
H
H
H
References and Notes
H
H
H
H
1
a) G. Zeni, R. C. Larock, Chem. Rev. 2004, 104, 2285. b) I.
Nakamura, Y. Yamamoto, Chem. Rev. 2004, 104, 2127. c) M.
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M. Tzamarioudaki, Z. Li, R. J. Donovan, Chem. Rev. 1996, 96,
635.
For pioneering studies of [3 + 2] cycloaddition of vinyl oxiranes
and olefins to furnish tetrahydrofurans, see: J.-G. Shim, Y.
Yamamoto, J. Org. Chem. 1998, 63, 3067.
aReactions were carried out using [Ni(cod)2] (10 mol %), IP-a
(20 mol %), 1 (0.5 mmol), and 2 (1.25 mmol) in toluene at
30 °C for 24 h. bReactions afford tetrahydrofurans 3 as a
mixture of inseparable diastereoisomers.
2
3
4
a) I. Koyama, T. Kurahashi, S. Matsubara, J. Am. Chem. Soc. 2009,
131, 1350. b) S. Sako, T. Kurahashi, S. Matsubara, Chem.
Commun. 2011, 47, 6150.
not afford the desired cycloadduct (Entry 3). A range of
¡,¢-unsaturated ketones 1 was also tested in the reaction with
2a. ¢-Aryl-substituted enones possessing an electron-donating
or -withdrawing group on the phenyl ring also provided
corresponding cycloadducts 3ea and 3fa in 81% and 76%
yields respectively (Entries 4 and 5). ¢-Naphthyl-substituted
enone 1g also participated in the reaction with 2a to give
tetrahydrofuran 3ga in 63% yield (Entry 6). The reaction of
¢-alkyl-substituted enone 1h provided the cycloadduct 3ha
in 71% yield (Entry 7). Enone 1i reacted with 2a to furnish
tetrahydrofuran 3ia in 51% yield (Entry 8).6
The formation of polysubstituted tetrahydrofuran 3aa can be
rationalized as arising from oxidative cyclization of nickel(0) to
an enone 1a to form oxa-nickelacycle 4 (Scheme 2). Subsequent
coordination of vinyl oxirane 2a and nucleophilic addition of
nickel enolate to vinyl oxirane 2a take place to afford six-
membered oxa-nickelacycle 5,5d,7 which undergoes reductive
elimination to give 3aa; the starting nickel(0) complex is
regenerated.
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Benzylidene-substituted pentane-2,4-dione 1b and diethyl malonate
1c failed to participate in the reaction with 2a, probably due to
difficulties in formation of oxa-nickelacycle intermediates with
nickel(0) catalyst.
For some selected examples of six-membered oxa-nickalacyle
intermediate formation, see: a) C. Molinaro, T. F. Jamison, J. Am.
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5
6
7
8
In conclusion, we have developed a new nickel-catalyzed
[3 + 2] cycloaddition of ¡,¢-unsaturated ketones with vinyl
oxiranes to provide polysubstituted tetrahydrofurans. We man-
ifested that the reaction is initiated by oxidative cyclization of
¡,¢-unsaturated ketones with nickel(0). Further efforts to
control the diastereoselectivity of the reaction are now in
progress.8
Supporting Information is available electronically on the CSJ-
Journal Web site, http://www.csj.jp/journals/chem-lett/index.html.
Chem. Lett. 2011, 40, 808-809
© 2011 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/