Nickel-catalyzed ring-opening three-component coupling of methylenecyclopropane with aldehydes and silanes

Article abstract of DOI:10.1021/ol101838q

A nickel-catalyzed three-component coupling between methylenecyclopropane, aldehydes, and silanes afforded silylated allylic alcohols that possess an alkyl substituent at the 2-position via cleavage of the proximal C - C bond of methylenecyclopropane.

Full text of DOI:10.1021/ol101838q

ORGANIC
LETTERS
2010
Vol. 12, No. 20
4536-4539
Nickel-Catalyzed Ring-Opening
Three-Component Coupling of
Methylenecyclopropane with Aldehydes
and Silanes
Kenichi Ogata,* Yuka Atsuumi, and Shin-ichi Fukuzawa*
Department of Applied Chemistry, Institute of Science and Engineering,
Chuo UniVersity, 1-13-27 Kasuga, Bunkyo-ku, Tokyo 112-8551, Japan
kogata@kc.chuo-u.ac.jp; orgsynth@kc.chuo-u.ac.jp
Received August 6, 2010
ABSTRACT
A nickel-catalyzed three-component coupling between methylenecyclopropane, aldehydes, and silanes afforded silylated allylic alcohols that
possess an alkyl substituent at the 2-position via cleavage of the proximal C-C bond of methylenecyclopropane.
Transition metal-catalyzed multicomponent reactions that
produce complex molecules from more than three parts of a
simple compound in one operation have become increasingly
important in recent organic syntheses.1 Noteworthy among
these is the convenient synthetic approach to allylic alcohols
by the nickel-catalyzed reductive three-component reaction
between an alkyne, aldehyde, and silane (or Lewis acid),
which has been reported by several research groups.2
Although many examples for the synthesis of allylic alcohols
possessing mono- and disubstituted alkenes by this method
have been reported, there are only a few examples of the
selective synthesis of allylic alcohols which possess a
monosubstituent at the 2-position. For example, Montgomery
reported highly regioselective access to a mono-2-position-
substituted silylated allylic alcohol by the reaction between
a terminal alkyne, aldehyde, and silane in the presence of a
nickel/N-heterocyclic carbene (NHC) catalyst.2m Jamison also
reported the synthesis of an allylic alcohol that possessed
an alkyl substituent in the 2-position by the nickel-catalyzed
reaction between an R-olefin, aldehyde, and silyl triflate.3
Recently, methylenecyclopropanes have been used as
versatile building blocks for nickel-catalyzed reactions
because of their unique reactivities.4 However, reductive
multicomponent couplings with methylenecyclopropane have
not been reported. In this report, we describe the first nickel/
NHC-catalyzed three-component coupling between methyl-
(1) Rubin, M.; Rubina, M.; Gevorgyan, V. Chem. ReV. 2007, 107, 3117.
(2) (a) Oblinger, E.; Montgomery, J. J. Am. Chem. Soc. 1997, 119, 9065.
(b) Tang, X.-Q.; Montgomery, J. J. Am. Chem. Soc. 1999, 121, 6098. (c)
Tang, X.-Q.; Montgomery, J. J. Am. Chem. Soc. 2000, 122, 6950. (d) Huang,
W.-S.; Chan, J.; Jamison, T. F. Org. Lett. 2000, 2, 4221. (e) Miller, K. M.;
Huang, W.-S.; Jamison, T. F. J. Am. Chem. Soc. 2003, 125, 3442. (f)
Mahandru, G. M.; Liu, G.; Montgomery, J. J. Am. Chem. Soc. 2004, 126,
3698. (g) Herath, A.; Montgomery, J. J. Am. Chem. Soc. 2006, 128, 14030.
(h) Sa-ei, K.; Montgomery, J. Org. Lett. 2006, 8, 4441. (i) Chaulagain,
M. R.; Sormunen, G. J.; Montgomery, J. J. Am. Chem. Soc. 2007, 129,
9568. (j) Baxer, R. D.; Montgomery, J. J. Am. Chem. Soc. 2008, 130, 9662.
(k) Saito, N.; Katayama, T.; Sato, Y. Org. Lett. 2008, 10, 3829. (l) Malik,
H. A.; Chaulagain, M. R.; Montgomery, J. Org. Lett. 2009, 11, 5734. (m)
Malik, H. A.; Sormunen, G. J.; Montgomery, J. J. Am. Chem. Soc. 2010,
132, 6304.
(3) (a) Ng, S.-S.; Jamison, T. F. J. Am. Chem. Soc. 2005, 127, 14194.
(b) Ho, C.-Y.; Jamison, T. F. Angew. Chem., Int. Ed. 2007, 46, 782.
10.1021/ol101838q  2010 American Chemical Society
Published on Web 09/10/2010

enecyclopropane, aldehydes, and silanes leading to silylated
allylic alcohols which possess an alkyl substituent in the
2-position with complete regioselectivity.
reaction was not observed. On the basis of this screening
of NHC and phosphine ligands, the highest yield for the
formation of 4 was achieved with IMes.
First, ligands and silanes were screened in the three-
component coupling of methylenecyclopropane 1a, ben-
zaldehyde 2a, and silane 3, as shown in Table 1. In the
Next, the Ni(cod)2/IMes-catalyzed three-component cou-
pling reaction was examined with use of various methyl-
enecyclopropanes and aldehydes as shown in Table 2.6 The
Table 1. Screening of Ligands and Silanes for the
Three-Component Coupling between 1a, 2a, and 3a
Table 2. Nickel-Catalyzed Three-Component Coupling between
1a-f, 2a-g, and 3a
a Ni(cod)2 (0.10 mmol), ligand (0.10 mmol), 1a (1.0 mmol), 2a (1.0
mmol), 3 (2.0 mmol), and THF (4 mL) were employed. b GC yield. c Isolated
yield.
presence of a catalyst derived from Ni(cod)2 and NHC
bearing a mesityl substituent (IMes) (1:1),5 the three-
component coupling using triisopropylsilane proceeded
smoothly at room temparature to afford 4aa in high yield
(entry 1). The use of triethylsilane resulted in a slightly
lower yield than that of triisopropylsilane (entry 2). In
comparison, tert-butyldimethylsilane was not effective,
and this reaction resulted in a complex mixture (entry 3).
The reaction with triisopropylsilane in the presence of
Ni(cod)2/PCy3 catalyst resulted in an extremely low yield
(entry 4). In this case, the ring-opening hydroacylation
product of methylenecyclopropane (γ,δ-unsaturated ke-
tone), which was reported by Suginome et al.,4e was also
detected as a byproduct by GC-MS. PnBu3 and PPh3 were
also ineffective for the reaction (entries 5 and 6). Using
other NHC ligands bearing 2,6-diisopropylphenyl and
isopropyl substituents, the three-component coupling
(4) Recently, much research for nickel(0)-catalyzed reaction using
methylenecyclopropane has been reported, for example: (a) Kamikawa, K.;
Shimizu, Y.; Takemoto, S.; Matsuzawa, H. Org. Lett. 2006, 8, 4011. (b)
Komagawa, S.; Saito, S. Angew. Chem., Int. Ed. 2006, 45, 2446. (c) Saito,
S.; Komagawa, S.; Azumaya, I.; Masuda, M. J. Org. Chem. 2007, 72, 9114.
(d) Shirakura, M.; Suginome, M. J. Am. Chem. Soc. 2009, 131, 5060. (e)
Taniguchi, H.; Ohmura, T.; Suginome, M. J. Am. Chem. Soc. 2009, 131,
11298. (f) Komagawa, S.; Takeuchi, K.; Sotome, I.; Azumaya, I.; Masu,
H.; Yamasaki, R.; Saito, S. J. Org. Chem. 2009, 74, 3323. (g) Yamasaki,
R.; Terashima, N.; Sotome, I.; Komagawa, S.; Saito, S. J. Org. Chem. 2010,
75, 480. (h) Saito, S.; Maeda, K.; Yamasaki, R.; Kitamura, T.; Nakagawa,
M.; Kato, K.; Azumaya, I.; Masu, H. Angew. Chem., Int. Ed. 2010, 49,
1830.
a Ni(cod)2 (0.10 mmol), IMes (0.10 mmol), 1 (1.0 mmol), 2 (1.0 mmol),
3 (2.0 mmol), and THF (4 mL) were employed. b Isolated yield.
use of electron-donating (p-methyl and p-methoxy-substi-
tuted) or electron-withdrawing (p- and m- fluoro-substituted)
(5) The N-heterocyclic carbene was prepared in situ by the reaction of
n
the corresponding imidazolium salt with BuLi.
Org. Lett., Vol. 12, No. 20, 2010
4537

arylaldehydes afforded product 4 in good to high yields
(entries 2-5). Reactions of 2f and 2g, which possess
heteroaryl groups, also proceeded to form the products 4af
and 4ag in good yields (entries 6 and 7). In contrast,
alkylaldehydes such as 1-pentanal and cyclohexylaldehyde
did not participate in the reaction.7
Scheme 3
Various methylenecyclopropanes were then reacted with
benzaldehyde 2a and triisopropylsilane 3 (Table 2, entries
8-13). The use of seven- and eight-memberd bicyclic
methylenecyclopropanes also afforded the corresponding
products 4ba and 4ca in high yields (entries 8 and 9).
The cis-dialkyl-chain-substituted methylenecyclopropane
1d-cis also participated in the reaction in high yield (entry
10), but the reaction with the corresponding trans
compound 1d-trans resulted in a lower yield of 4da (entry
11). The cis-ethyl-substituted methylenecyclopropane 1e
also participated in this reaction in high yield (entry 12).
The reaction with cyclohexyl-substituted methylenecy-
clopropane 1f, which has two nonequivalent proximal
C-C bonds, proceeded with selective cleavage of the less
hindered bond to give the corresponding product 4fa,
albeit with low yield (entry 13).
proximal C-C bond of methylenecyclopropane 1 to
nickel(0) affords 2-alkylidene-1-nickelacyclobutane in-
termediate A. The formation of a 2-alkylidene-1-nickela-
cyclobutane complex from the nickel(0) complex system
by reaction with methylenecyclopropane has been pro-
posed previously.4a,10,11 Next, the Ni-C bond of intermedi-
ate A undergoes insertion into aldehyde 2 to give interme-
diate B. In addition to this mechanism, the formation of
metallacycle C, followed by ring-opening is also possible.12
This is followed by cleavage of the nickel-oxygen bond by
σ-bond metathesis of the nickelacycle with triisopropylsilane
(D) to afford hydride- nickel intermediate E.2 Finally,
reductive elimination from E occurs to afford the silylated
allylic alcohol derivative 4.
To obtain insight into the mechanism of the reaction,
reactions with deuterium-labeled aldehydes and silanes were
carried out. The reaction between 1a, benzaldehyde-d1 (2a-
D), and triisopropylsilane 3 in the presence of Ni(cod)2/IMes
catalyst afforded compound 5 (Scheme 1). In compound 5,
Scheme 1
In summary, we have demonstrated the first three-
component coupling between methylenecyclopropane, an
aldehyde, and a silane leading to a silylated allylic alcohol
that possesses an alkyl substituent in the 2-position using
Ni(cod)2/N-heterocyclic carbene as the catalyst. The reactions
the position of the deuterium incorporation8 showed that
oxidative addition of the aldehydic C-H bond did not occur
in the reaction. Reaction of 1b, 2a, and triisopropylsilane-
d1 (3-D) by Ni(cod)2/IMes catalyst afforded the product 6,
which incorporated deuterium in the cycloalkyl group
(Scheme 2).9
(6) In these reactions, almost all methylenecyclopropane molecules were
consumed.
(7) In this reaction, complex mixtures were formed.
(8) In the 1H NMR of 5, the signal of the proton (5.19 ppm), which
was observed in the mesearment of 4aa, disappeared, and in 13C NMR, the
triplet signal (JCD ) 21.6 Hz) assignable to the silylated alcohol attached
carbon was also detected at 77.5 ppm.
Scheme 2
(9) The triplet signal (JCD ) 19.2 Hz) assignable to deuterium attached
alkyl carbon was detected at 36.1 ppm in 13C NMR.
(10) (a) Noyori, R.; Odagai, T.; Talaya, H. J. Am. Chem. Soc. 1970,
92, 5780. (b) Noyori, R.; Kumagai, Y.; Umeda, I.; Takaya, H. J. Am. Chem.
Soc. 1972, 94, 4018.
(11) (a) Kawasaki, T.; Saito, S.; Yamamoto, Y. J. Org. Chem. 2002,
67, 4911. (b) Ohashi, M.; Taniguchi, T.; Ogoshi, S. Organometallics 2010,
29, 2386.
(12) We could not rule out the possibility of mechanism via intermediate
C. In nickel-catalyzed dimerization of methylenecyclopropane, the formation
of a nickelacycle intermediate containing a cyclopropane ring, followed by
cyclopropropenyl-butenyl rearrangement was also proposed. See: Binger,
P.; Doyle, M. J.; Benn, R. Chem. Ber 1983, 116, 1, and ref 11.
A possible pathway for the three-component coupling
is shown in Scheme 3. First, oxidative addition of the
4538
Org. Lett., Vol. 12, No. 20, 2010

proceeded selectively via the cleavage of the proximal C-C
bond of methylenecyclopropane.
Supporting Information Available: Standard experimen-
tal procedure and characterization data for new compounds.
This material is available free of charge via the Internet at
http://pubs.acs.org.
Acknowledgment. This work was supported by The
Sumitomo Fundation. The authors are grateful to Prof. Ken
Tanaka (Tokyo University of Agriculture and Technology)
for obtaining HR-MS spectromeric data for some com-
pounds.
OL101838Q
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4539