Nickel-catalyzed direct conjugate addition of simple alkenes to enones

Article abstract of DOI:10.1021/ja903510u

(Chemical Equation Presented) A direct conjugate addition of simple alkenes to enones has been achieved in the presence of a Ni(0)/PCy₃ catalyst.

Full text of DOI:10.1021/ja903510u

Published on Web 07/10/2009
Nickel-Catalyzed Direct Conjugate Addition of Simple Alkenes to Enones
Sensuke Ogoshi,* Toshifumi Haba, and Masato Ohashi
Department of Applied Chemistry, Graduate School of Engineering, Osaka UniVersity, Suita,
Osaka 565-0871, Japan
Received April 30, 2009; E-mail: ogoshi@chem.eng.osaka-u.ac.jp
The introduction of an alkenyl group at the ꢀ-position of an enone
by the addition of a C-H bond of a simple alkene has not been
achieved because C-H bonds of simple alkenes are less reactive
toward transition metals than those of enones (eq 1). In fact, the
insertion of alkenes into the C-H bond of enones to give more
substituted R,ꢀ-unsaturated carbonyl compounds occurs in the pre-
sence of ruthenium catalysts, since the oxidative addition of the
C-H bond of an enone to ruthenium occurs prior to that of the
simple alkenes (eq 2).1-3 A nickel-catalyzed hydroalkenylation is
also a potential method used to achieve a direct conjugate addition
of alkenes to enones, although no example of the hydroalkenylation
of enones with simple alkenes to form a carbon-carbon bond at
the ꢀ-position has been reported.4 To date, employing alkenyl metal
compounds has been indispensable for the introduction of an alkenyl
group at the ꢀ-position of an enone by conjugate addition (eq 3).5,6
Although a variety of alkenyl groups are available for this reaction,
the preparation of alkenyl metal compounds is required. Recently,
Jamison reported a nickel-catalyzed reaction of enones with alkenes
in the presence of Et3SiOTf and Et3N to give enol silyl ethers, which
is a more straightforward method for introducing an alkenyl group
at the ꢀ-position of enones.7 However, to date, direct conjugate
addition of alkenes to enones remains an elusive goal.
reaction of 1 with Ni(cod)2 and PBu3, the formation of en-enone 3, an
isomer of 1, was observed. Formally, these nickel complexes can be
generated by the intramolecular oxidative cyclization of 3 with nickel(0)
complexes. Thus, we confirmed the occurrence of oxidative cyclization
by the reaction of 3 with Ni(cod)2 and PBu3 at 100 °C to give 2b
quantitatively (Scheme 1), in which carbon-carbon bond formation
occurred at the ꢀ-position of the carbonyl group.10 The formation of
an η3-oxaallylnickel moiety might stabilize the generated complex and
control the regiochemistry, leading to formation of a carbon-carbon
bond at the ꢀ-position. The reaction was expanded to an intermolecular
reaction, and we chose (E)-1-phenylbut-2-en-1-one (4a) as the enone
and styrene as the alkene for the first combination. A stoichiometric
reaction of 4a and styrene with Ni(cod)2 and PCy3 was carried out.
The formation of a µ-η2-enonenickel dimer complex was observed at
room temperature.8a Heating at 60 °C for 48 h led to the formation of
the expected direct conjugate addition product 5 in 88% yield (eq 4):
In the intramolecular reaction, carbon-carbon bond formation between
the ꢀ-carbon and the internal carbon of the styryl moiety occurred. In
the intermolecular reaction, formation of a carbon-carbon bond
between the terminal carbon of styrene and the ꢀ-carbon of 4a
occurred. These results inspired us to construct a nickel-catalyzed direct
conjugate addition reaction of simple alkenes to enones, as shown in
eq 1.
Scheme 1. Oxidative Cyclization of Alkene and Enone with Ni(0)
In the course of the study of the nickel-catalyzed [3 + 2]
cycloaddition of cyclopropyl ketones,8 the reaction of 2-vinylphenyl
cyclopropyl ketone (1) with a nickel(0) complex was carried out to
trap a cyclopropyl group with an intramolecular carbon-carbon double
bond. Unexpectedly, an insoluble black crystal was obtained in 58%
isolated yield, and X-ray crystallography showed that it has a dimeric
nickelacycle structure (2a in Scheme 1). Similarly, the reaction of 1
with Ni(cod)2 and PBu3 also gave the corresponding soluble complex
2b in 57% isolated yield. The Ni-C(carbonyl) distance of 2.4143(18)
Å in 2b is intermediate between that found in η1-C-enolate nickel
complexes (2.990 and 2.938 Å)9 and that observed in η3-oxaallylnickel
complexes [2.024(3) and 2.034(4) Å].8b The 13C NMR signal attribut-
able to the carbonyl carbon of 2b appears at δ 176, which is shifted
to higher field by 30 ppm relative to that observed in the η1-C-enolate
nickel complex Cp*Ni(PPh3)CH2COPh (δ 206)9a and is close to those
for η3-oxaallylnickel complexes (δ 160).8b These facts suggest that
the contribution of the η3-oxaallyl structure to 2b might be larger than
that of the η1-C-enolate structure in solution. At an early stage of the
In the presence of a catalytic amount of Ni(cod)2 and PCy3, however,
only a trace amount of 5 was obtained, and the precipitation of nickel
black was observed. To suppress the formation of nickel black, the
reaction was carried out in the presence of 4 equiv of PCy3 at 100 °C
for 4 h. Although 4a was consumed, the expected direct conjugate
addition product was obtained in only 39% yield because of the
formation of oligomers of 4a. In fact, in the absence of styrene, 4a
was consumed under the same reaction conditions to give a mixture
of oligomers. Thus, in the presence of 2 equiv of styrene, 4a was added
slowly at 100 °C to avoid the occurrence of oligomerization, and 5
was obtained in 91% yield (Table 1, entry 1). Similarly, the reactions
of 4a with 4-trifluoromethylstyrene, 4-methoxystyrene, and 4-tert-
9
10350 J. AM. CHEM. SOC. 2009, 131, 10350–10351
10.1021/ja903510u CCC: $40.75  2009 American Chemical Society

C O M M U N I C A T I O N S
butylstyrene occurred to give the corresponding direct conjugate
addition products 6, 7, and 8 (entries 2-4). Moreover, both octene
and decene could also be employed as nucleophiles for 4a to give the
expected products 9 and 10 as mixtures of E and Z isomers in high
yields (entries 5 and 6). The regioselectivity contrasted with that
observed in Jamison’s work.7 A prolonged reaction time and a higher
concentration were required. This might be due to a weaker coordina-
tion of 1-octene and 1-decene to the nickel(0) center, since the
simultaneous coordination of an enone and an alkene to nickel(0) is
required to undergo oxidative cyclization.11 Similarly, (E)-1-phenylhex-
2-en-1-one (4b) reacted with styrenes under the same reaction
conditions to give the expected products (11, 12, 13) in high yields
(entries 7-9). The reaction of (E)-3-penten-2-one (4c) with the same
alkenes also occurred, affording the corresponding conjugate addition
products (14, 15, 16) in moderate to high yields (entries 10-12). The
reaction of 4c with 1-octene gave an inseparable mixture of a trace
mount of products and oligomers of 4c.12 Under the same reaction
conditions, (E)-2-butenal underwent polymerization to give an insoluble
white powder. Although 2a and 2b could be isolated as nickelacycle
complexes, intramolecular direct conjugate addition of an alkene to
an enone in 4d proceeded catalytically to give the expected cyclic
compound 17 (entry 13). The phenyl group and benzyl carbon of the
styryl moiety in 4d are on opposite sides of the double bond. On the
other hand, those in 17 are on the same side. These observations
suggest that rotation of the double bond and abstraction of the hydrogen
on the same side as the phenyl group might occur during the reaction.
The coordination ability of enones toward the nickel(0) center is
much stronger than that of the simple alkenes. Therefore, a slow
addition of enones might be required in order to carry out the
reaction at a low enone concentration, thereby simultaneously
coordinating enones and alkenes and avoiding the occurrence of
oligomerization of the enones.
Scheme 2. Plausible Reaction Path
In conclusion, we have demonstrated the first example of a direct
conjugate addition of simple alkenes to enones catalyzed by a
nickel(0) complex. This reaction is a very straightforward method
for the introduction of an alkenyl group at the ꢀ-position of enones,
since the conventional conjugate addition method requires the
preparation of alkenyl metals and its metal must be discarded after
the reaction. The regiochemistry of the carbon-carbon bond at the
ꢀ-position might be controlled by the formation of an η3-
oxaallylnickel species that might stabilize the generated intermediate.
Acknowledgment. This work was supported by a Grant-in-Aid
for Scientific Research (21245028), a Grant-in-Aid for Scientific
Research on Priority Areas (19028038, Chemistry of Concerto
Catalysis), and Encouragement for Young Scientists (B) (21750102)
from MEXT.
Table 1. Nickel-Catalyzed Direct Conjugate Additiona
Supporting Information Available: Detailed experimental proce-
dures, analytical and spectral data for all new compounds, and
crystallographic data (CIF) for 2a and 2b. This material is available
free of charge via the Internet at http://pubs.acs.org.
References
(1) Sato, T.; Kakiuchi, F.; Chatani, N.; Murai, S. Chem. Lett. 1998, 893.
(2) Kakiuchi, F.; Tanaka, Y.; Sato, T.; Chatani, N.; Murai, S. Chem. Lett. 1995,
679.
(3) Trost, B. M.; Imi, K.; Davies, I. W. J. Am. Chem. Soc. 1995, 117, 5371.
(4) (a) Review: Babu, T. V. R. Chem. ReV. 2003, 103, 2845. (b) Ni: Muller,
G.; Ordinas, J. I. J. Mol. Catal. A 1997, 125, 97. (c) Ru: He, Z.; Yi, C. S.;
Donaldson, W. A. Synlett 2004, 1312. (d) Ru: Yi, C. S.; He, Z.; Lee, D. W.
Organometallics 2001, 20, 802.
(5) (a) Perlmutter, P. Conjugate Addition Reactions in Organic Chemistry;
Tetrahedron Organic Chemistry Series, Vol. 7; Elsevier: Amsterdam, 1992;
p 63. (b) Hayashi, T.; Yamasaki, K. Chem. ReV. 2003, 103, 2829.
(6) Nickel-catalyzed coupling reactions of enones and alkynes with organotin
or organozinc compounds can also give an alkenylated compounds. See:
(a) Review: Ikeda, S.-i. Acc. Chem. Res. 2000, 33, 511. (b) Montgomery,
J. Angew. Chem., Int. Ed. 2004, 43, 3890. (c) Herath, A.; Thompson, B. B.;
Montgomery, J. J. Am. Chem. Soc. 2007, 129, 8712.
(7) Ho, C.-Y.; Ohmiya, H.; Jamison, T. F. Angew. Chem., Int. Ed. 2008, 47,
1893.
(8) (a) Ogoshi, S.; Nagata, M.; Kurosawa, H. J. Am. Chem. Soc. 2006, 128,
5350. (b) Tamaki, T.; Nagata, M.; Ohashi, M.; Ogoshi, S. Chem.sEur. J.
2009, in press. (c) Liu, L.; Montgomery, J. J. Am. Chem. Soc. 2006, 128,
5348.
(9) (a) Burkhardt, E. R.; Bergman, R. G.; Heathcock, C. H. Organometallics
´
1990, 9, 30. (b) Ca´mpora, J.; Matas, I.; Palma, P.; Alvarez, E.; Graiff, C.;
a General conditions: 2:1 alkene/enone, Ni(cod)2 (10 mol %), PCy3
(40 mol %), 100 °C, slow addition over 5 h followed by additional
heating for 2 h. GC yields are given, with isolated yields in parentheses.
b Additional heating for 4 h. c 10:1 alkene/enone. d 64:46 E/Z. e 58:42 E/
Z. f Ni(cod)2 (5 mol %), PCy3 (20 mol %), 2.5 h. g NMR Yield.
Tiripicchio, A. Organometallics 2007, 26, 5712.
(10) The oxidative cyclization of an enone and an alkyne to give an O-nickel
enolate has been reported by Montgomery and Schlegel. See: (a) Amaras-
inghe, K. K. D.; Chowdhury, S. K.; Heeg, M. J.; Montgomery, J.
Organometallics 2001, 20, 370. (b) Hratchian, H. P.; Chowdhury, S. K.;
Gutie´rrez-Garc´ıa, V. M.; Amarasinghe, K. K. D.; Heeg, M. J.; Schlegel,
H. B.; Montgomery, J. Organometallics 2004, 23, 4636.
A plausible reaction path is depicted in Scheme 2. Oxidative
cyclization of an enone and an alkene to generate an η3-
oxaallylnickelacycle occurs, followed by ꢀ-hydrogen elimination
and reductive elimination to give direct conjugate addition products.
(11) Ogoshi, S.; Oka, M.; Kurosawa, H. J. Am. Chem. Soc. 2004, 126, 11802.
(12) The formation of a trace amount of conjugate addition products was
observed by GC-MS.
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