Synthesis of five- and six-membered benzocyclic ketones through intramolecular alkene hydroacylation catalyzed by Nickel(0)/N-Heterocyclic Carbenes

Article abstract of DOI:10.1002/anie.201206186

Getting some closure: Mechanistic studies supported the participation of an oxanickelacycle complex in the hydroacylation step of the title reaction, which proceeds without decarbonylation even in the absence of well-known chelation assistance by heteroatoms. Copyright

Full text of DOI:10.1002/anie.201206186

Angewandte
Chemie
DOI: 10.1002/anie.201206186
Organometallic Catalysis
Synthesis of Five- and Six-Membered Benzocyclic Ketones through
Intramolecular Alkene Hydroacylation Catalyzed by Nickel(0)/N-
Heterocyclic Carbenes**
Yoichi Hoshimoto, Yukari Hayashi, Haruka Suzuki, Masato Ohashi, and Sensuke Ogoshi*
Transition-metal-catalyzed hydroacylation has been accepted
as a promising synthetic method to form carbon–carbon
bonds between an aldehyde and unsaturated compounds,
such as alkenes, alkynes, and ketones. A number of catalyst
systems have been developed, and high enatio-, regio-, and
chemo-selectivity has been achieved.[1] Despite these exten-
sive efforts and praiseworthy results, an inevitable side
reaction persists: decarbonylation from an acyl metal inter-
mediate, which causes a decrease in atom-efficiency and
a deactivation of the catalyst through the coordination of
carbon monoxide (Scheme 1, path a).[1,2] Major advances in
that the former was more plausible because of the formation
of decarbonylated olefinic products in the reaction with
benzaldehyde. On the other hand, during the course of our
research on heteronickelacycles,[7] we demonstrated that an
oxanickelacycle prepared by oxidative cyclization of an
alkyne and an aldehyde with Ni0 slowly decomposed to
furnish an a,b-enone and no decarbonylated product.[7b] This
result indicated that the oxanickelacycle can act as a potential
intermediate in Ni0-catalyzed alkyne hydroacylation
(Scheme 1, path b). We also reported the Ni0-catalyzed
crossed- and homodimerization of aldehydes to give esters.
Although it can be regarded as the hydroacylation of an
aldehyde, the undesired decarbonylation was not obser-
ved.[7c,d] The results of kinetic experiments are consistent
with the participation of a dioxanickelacycle intermediate in
the reaction path.
The formation of dimeric oxanickelacycles in the stoi-
chiometric reaction of o-allylbenzaldehyde (1a), [Ni(cod)2]
(cod = 1,5-cyclooctadiene), and tertiary phosphines has been
reported as well.[7a] Thus, the construction of a catalytic
alkene hydroacylation through an oxanickelacycle seems
quite effective for the generation of a benzocyclic ketone
without decarbonylation (Scheme 2). Given the importance
of benzocyclic ketones, the structural motifs of which have
Scheme 1. Transition-metal-catalyzed alkyne hydroacylation through
a) an acyl metal intermediate or b) a nickelacycle intermediate.
M=Rh, Ru, Co, Ir, Ni, or Pd.
hydroacylation have been associated with the development of
strategies to suppress decarbonylation.[3,4] Thus, in the interest
of promoting further progress, it is worthwhile to provide an
alternative strategy to avoid decarbonylation.
Tsuda and Saegusa et al. reported Ni0/PR3-catalyzed
intermolecular alkyne hydroacylation to give a,b-enones.[5,6]
They proposed two possible reaction pathways: a) proceeds
through an acyl nickel intermediate, and b) proceeds through
an oxanickelacycle intermediate (Scheme 1). They concluded
Scheme 2. Catalytic generation of a benzocyclic ketone without decar-
bonylation.
been found in the synthetic intermediates of numerous
biologically active natural products and medicinal agents,[8,9]
this new approach is an attractive method. Herein, we report
an intramolecular alkene hydroacylation catalyzed by a Ni0/
N-heterocyclic carbene (NHC) complex that yields a variety
of five- and six-membered benzocyclic ketones. Mechanistic
studies that include stoichiometric reactions and the isolation
of the oxanickelacycle intermediate are also discussed.
An optimization of the reaction conditions for the intra-
molecular hydroacylation of 1a was conducted.[10] NHCs with
an N-alkyl-substituent, such as ItBu and IAd, gave
2-methylindanone (2a) in excellent yields, whereas PPh3,
[*] Y. Hoshimoto, Y. Hayashi, H. Suzuki, Dr. M. Ohashi, Prof. S. Ogoshi
Department of Applied Chemistry, Faculty of Engineering, Osaka
University, Suita, Osaka 565-0871 (Japan)
E-mail: ogoshi@chem.eng.osaka-u.ac.jp
[**] This work was supported by a Grant-in-Aid for Scientific Research
(No. 21245028) and for Scientific Research on Innovative Area
“Molecular Activation Directed toward Straightforward Synthesis”
(No. 23105546) from MEXT, and the Asahi Glass Foundation. Y.H.
expresses his special thanks for the research fellowships for young
scientists from the Japan Society for the Promotion of Science
(JSPS).
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201206186.
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PCy3, and N-aryl-substituted NHCs were not effective. We
found that the treatment of 1a at 1308C for 5 h in the
presence of [Ni(cod)2]/ItBu (5 mol%) in mesitylene resulted
in the formation of 2a, which was isolated in 98% yield.
The scope of the reaction was investigated with respect to
o-allylbenzaldehyde derivatives 1a–j (Scheme 3). When an
electron-donating group was bonded to the benzene ring (1b–
e), the hydroacylation proceeded to give the corresponding
indanones, which were isolated in > 93% yield.[11] Fluorine-
substituted product 2 f was obtained in moderate yield.
Chlorine-substituted 1g did not afford the corresponding
ketone 2g and was recovered in 95% yield after isolation. In
was required, 1h was successfully converted into 2h in 92%
yield. This method can also be applied to substituted allyl
groups (1i and 1j) to give the corresponding ketones (2i and
2j) in moderate to good yields. Furthermore, we applied the
method to the hydroacylation of o-homoallylbenzaldehyde
derivatives 1k–p. For reported transition-metal-catalyzed
alkene hydroacylations, the formation of six-membered (or
larger) ring systems is difficult,[3,12–14] as the rate of the ring-
closing step is much slower than that of the decarbonylation
from an acyl metal intermediate.[1a] Thus, the introduction of
suitable chelation assistance by heteroatoms has been essen-
tial for stabilizing the acyl metal intermediate.[3] By contrast,
in the Ni0/ItBu-catalyst system, the formation of 1-tetralone
derivatives was successfully achieved in excellent yields (2k–
o, up to 99% yield) without the need for chelation assistance.
A decrease in yield was observed in the case of 2p, and the
decarbonylated olefinic product, 2-methyl-4-phenylbutene,
was also detected in 2% yield by GC analysis (see below).
The presented Ni0-catalyzed hydroacylation is 100%
atom-efficient and generates no waste. Thus, it is a highly
environmentally favorable route to 1-indanone and 1-tetra-
lone derivatives.[7,8,15] The most common approach to these
compounds has been the intramolecular Friedel–Crafts
acylation with conventional conditions that require excess
amounts of acid promoters and high temperatures, particu-
larly for the formation of 1-indanone.[16] Thus, the approach
for the preparation of five- and six-membered benzocyclic
ketones demonstrated here has synthetic utility.
this case, o-allylbenzaldehyde was detected by GC-MS, thus
0
À
the oxidative addition of an Ar Cl bond to Ni might
deactivate the catalyst. Although [Ni(cod)2]/ItBu (10 mol%)
To gain insight into the reaction mechanism, some
stoichiometric reactions were conducted (Scheme 4). The
treatment of 1a with [Ni(cod)2] and ItBu in C6D6 (or toluene)
2
2
=
at 228C resulted in the quantitative formation of (h :h -CH2
CHCH2C6H4CHO)Ni(ItBu) (C1a) within 5 min, which was
isolated in 83% yield. Complex C1a was converted into
dimeric oxanickelacycle C2a’, which was isolated in 84%
yield (228C, 33 days). The monomeric complex C2a was not
observed by NMR spectroscopy; however, it is logical that
C2a’ was formed through the dimerization of C2a. The
Scheme 3. Ni0-catalyzed intramolecular alkene hydroacylation. Reaction
conditions: Enal 1a–p (0.80 mmol), [Ni(cod)2]/ItBu (5 mol%,
0.040 mmol) and mesitylene (2 mL) were reacted at 1308C. Yields
presented are of isolated product; yields determined by GC analysis
using n-pentadecane as an internal standard are given in parentheses.
[a] [Ni(cod)2] (7 mol%) and ItBu (5 mol%) in toluene were used.
[b] [Ni(cod)2]/ItBu (10 mol%) was used. [c] [Ni(cod)2]/IMes (10 mol%)
was used. cod=1,5-cyclooctadiene (For the structures of ItBu and
IMes, see the Supporting Information).
Scheme 4. Stoichiometric reactions with 1a and proposed reaction
pathways. See text for details on the structure of C2a’.
2
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structure of C2a’ in solution was identified by NMR as
a mixture of two isomers, syn-C2a’ and anti-C2a’. Moreover,
the molecular structure of anti-C2a’ was confirmed by X-ray
crystallography (Figure 1a). We also observed the conversion
of C2a’ into the hydroacylated ketone 2a in 32% yield when
C2a’ was heated at 1308C for 24 h (32% conv.).[17] Compared
with the catalytic reaction, the generation of 2a from C2a’ at
1308C was significantly slower. However, in the presence of
2.5 mol% C2a’, 2a was obtained in 101% from both 1a and
C2a’ (maximal yield of 2a is 105%) within 5 h. These results
indicate that the formation of C2a’ has no significant
influence on catalytic efficiency under the catalytic reaction
conditions.
ylation occurs through (h2:h2-enal)Ni(ItBu) complex C1 or
not (Scheme 5). Both 1k and 1p quantitatively reacted with
[Ni(cod)2]/ItBu to give C1k and C1p, respectively. The
structure of C1k was confirmed by X-ray analysis (Fig-
The stoichiometric reaction of 1k or 1p with [Ni(cod)2]/
ItBu was also examined to confirm whether the decarbon-
Scheme 5. Stoichiometric reactions with 1k and 1p.
ure 1b). Thermolysis of C1k or C1p in C6D6 at 608C for 36 h
resulted in the quantitative formation of the corresponding
tetralone derivatives (2k or 2p) with the regeneration of
[Ni(cod)2]/ItBu.[18] Although a small amount of the decar-
bonylated olefinic product was observed in the catalytic
reaction of 1p, no decarbonylated product was observed by
1H NMR or GC-MS analysis during the formation of 2p from
C1p. Based on these results, C1p afforded 2p exclusively, and
the lower yield of 2p vs. 2k in the catalytic reaction could be
rationalized by the slower formation of C1p (24 h) vs. C1k
(30 min).
This intramolecular hydroacylation might proceed
through the steps shown in Scheme 4. The coordination of
1 to Ni0/L gives rise to C1 (step a) and the oxidative
cyclization then takes place to give the monomeric nickela-
cycle intermediate C2 (step b). Finally, b-hydride elimination
and reductive elimination occur to give 2, along with
regeneration of the catalyst (step c).[19]
In conclusion, we have developed the first Ni0/NHC-
catalyzed intramolecular hydroacylation. A variety of inda-
none derivatives were prepared in good to excellent yields.
Notably, the synthesis of tetralone derivatives, which were
difficult to prepare by the reported hydroacylation systems
without chelation assistance, was also achieved. The enal-
coordinated complex C1 and the dimeric oxanickelacycle C2’
were isolated. The transformation of C2’ into the correspond-
ing ketone under both stoichiometric and catalytic conditions
was also observed, which indicated the participation of the
oxanickelacycle complex (as a monomeric and/or dimeric
structure) in the presented hydroacylation. This work pro-
vides a novel design for alkene hydroacylation that proceeds
without the decarbonylation, that is, the simultaneous coor-
dination of both olefin and formyl moieties to Ni0 followed by
oxidative cyclization to give the oxanickelacycle. Further
studies on the reaction mechanism (kinetics and computa-
tional chemistry) are ongoing in our laboratory.
Received: August 2, 2012
Published online: && &&, &&&&
Figure 1. Molecular structure of a) anti-C2a’ and b) C1k with thermal
ellipsoids set at 50% probability. Calculated hydrogen atoms are
omitted for clarity.
Keywords: homogeneous catalysis · hydroacylation · ketones ·
nickel · transition metals
.
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4
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Angew. Chem. Int. Ed. 2012, 51, 1 – 5
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Communications
Organometallic Catalysis
Y. Hoshimoto, Y. Hayashi, H. Suzuki,
M. Ohashi, S. Ogoshi*
&&&& — &&&&
Synthesis of Five- and Six-Membered
Benzocyclic Ketones through
Intramolecular Alkene Hydroacylation
Catalyzed by Nickel(0)/N-Heterocyclic
Carbenes
Getting some closure: Mechanistic stud-
ies supported the participation of an
oxanickelacycle complex in the hydroacy-
lation step of the title reaction, which
proceeds without decarbonylation even in
the absence of well-known chelation
assistance by heteroatoms.
Angew. Chem. Int. Ed. 2012, 51, 1 – 5
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
5
These are not the final page numbers!