Synthesis, Characterization, and unique catalytic activities of a fluorinated nickel enolate

Article abstract of DOI:10.1021/ja511730k

We have synthesized a new nickel enolate [(PhCOCF₂)Ni(dcpe)][FB(C₆F₅)₃] featuring fluorine atoms on the enolate moiety via B(C₆F₅)₃-promoted C-F bond activation of α,α,α-trifluoroacetophenone. X-ray diffraction study of [(PhCOCF₂)Ni(dcpe)][FB(C₆F₅)₃] revealed that the complex had adopted an η³-oxallyl coordination mode in the crystal lattice. The reaction of ^tBuNC with [(PhCOCF₂)Ni(dcpe)][FB(C₆F₅)₃] resulted in the coordination of isocyanide to the nickel center to form a C-bound enolate complex. The reactions of [(PhCOCF₂)Ni(dcpe)][FB(C₆F₅)₃] with aldehydes gave insertion products quantitatively which were fully characterized by NMR spectroscopy. Furthermore, we established unique catalytic applications for [(PhCOCF₂)Ni(dcpe)][FB(C₆F₅)₃] toward a Tishchenko reaction, along with a highly selective crossed-esterification of α,α,α-trifluoroacetophenones with aldehydes.

Full text of DOI:10.1021/ja511730k

Article
pubs.acs.org/JACS
Synthesis, Characterization, and Unique Catalytic Activities of a
Fluorinated Nickel Enolate
Ryohei Doi,† Kotaro Kikushima,† Masato Ohashi,*,† and Sensuke Ogoshi*,†,‡
†Department of Applied Chemistry, Faculty of Engineering, Osaka University, Suita, Osaka 565-0871, Japan
‡ACT-C, Japan Science and Technology Agency (JST), Suita, Osaka 565-0871, Japan
S
* Supporting Information
ABSTRACT: We have synthesized a new nickel enolate
[(PhCOCF2)Ni(dcpe)][FB(C6F5)3] featuring fluorine atoms on
the enolate moiety via B(C6F5)3-promoted C−F bond activation
of α,α,α-trifluoroacetophenone. X-ray diffraction study of
[(PhCOCF2)Ni(dcpe)][FB(C6F5)3] revealed that the complex
had adopted an η3-oxallyl coordination mode in the crystal lattice.
t
The reaction of BuNC with [(PhCOCF2)Ni(dcpe)][FB(C6F5)3]
resulted in the coordination of isocyanide to the nickel center to
form a C-bound enolate complex. The reactions of [(PhCOCF2)-
Ni(dcpe)][FB(C6F5)3] with aldehydes gave insertion products
quantitatively which were fully characterized by NMR spectroscopy. Furthermore, we established unique catalytic applications for
[(PhCOCF2)Ni(dcpe)][FB(C6F5)3] toward a Tishchenko reaction, along with a highly selective crossed-esterification of α,α,α-
trifluoroacetophenones with aldehydes.
their chemistry, only a few examples of fluorinated transition-
metal enolates have been established due to a lack of readily
accessible synthetic routes. To date, oxidative addition of a C−
Cl bond to Pt(0) is the only method that has been used to
successfully obtain the fluorinated analogues of transition-metal
enolates (Figure 1b).5 Moreover, α-halogenated fluoroketones
(such as A and B) are neither easy to prepare nor commercially
available. Therefore, trifluoromethylketones could be ideal
candidates for the precursors of fluorinated transition-metal
enolates when using the well-established preparative procedure
making use of inexpensive trifluoroacetic acid derivatives as
starting materials.6 Amii and Uneyama have reported pioneer-
ing work that demonstrates an efficient synthetic method to
gain fluorinated-silyl enolates via the treatment of α,α,α-
trifluoroacetophenone with magnesium metal and chlorotrime-
thylsilane via C−F bond activation (Figure 1c).7 As far as we
could ascertain, there is no precedence for the synthesis of
fluorinated transition-metal enolates from trifluoromethylke-
tones. Recently, we developed a Lewis acid-promoted C−F
bond activation of perfluoroalkenes8 and perfluoroarenes9 on
Pd(0) or Ni(0) to afford a series of fluorinated organometallic
complexes. In those reactions, the Lewis acids that were
effective were those bearing a strong affinity with fluoride
anions such as lithium, magnesium, aluminum, and boron
compounds.10 Herein, we report a C−F bond activation of
α,α,α-trifluoroacetophenone coordinated to Ni(0) promoted
by the addition of B(C6F5)3, which gives the first example of
fluorinated Ni(II) enolate. Furthermore, a unique catalytic
INTRODUCTION
■
The synthesis, structure, and reactivity of transition-metal
enolates continues to garner interest because of their important
roles in various organic transformations.1 Many transition-metal
enolates have been prepared via the nucleophilic displacement
of carbonyl compounds bearing a leaving group at the α-
position, via the transmetalation of a transition-metal salt with
the enolate of a main group element and the oxidative
cyclization of α,β-unsaturated carbonyl compounds on
Ni(0).2−4 These reactions result in the formation of
transition-metal enolates with coordination modes that are
classified as either O-bound, C-bound, or η3-oxallyl, although
most main group elements preferentially bind to the oxygen
atom of an enolate (Figure 1a). Despite numerous studies on
Figure 1. (a) Coordination modes of transition-metal enolates. (b)
Fluorinated platinum enolates obtained via C−Cl bond cleavage. (c)
Synthesis of fluorinated silyl enolate from readily available
trifluoromethylketones. (d) This work: Synthesis of fluorinated Ni(II)
enolate starting from α,α,α-trifluoroacetophenone.
Received: November 14, 2014
© XXXX American Chemical Society
A
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activity of the nickel enolate has been demonstrated for the
crossed-esterification of aldehydes with α-fluorinated ketones.
RESULTS AND DISCUSSION
■
We recently reported the selective C−F bond activation of a
CF3 group of hexafluoropropylene on Pd(0) via the addition of
B(C6F5)3 (1).8d Thus, the C−F bond cleavage of α,α,α-
trifluoroacetophenone (2a) was also expected by the
combination of 1 and low valent transition metals. There are
some reports dealing with η2-ketone complexes of Ni(0),
including the ones bearing trifluoromethylketones.11,12 For
instance, Yamamoto et al. have described the synthesis of (η2-
Figure 2. ORTEP representation of the cation of 4 with thermal
ellipsoids at the 50% probability level. H atoms and the [FB(C6F5)3]
counteranion were omitted for clarity. Selected bond lengths (Å):
Ni−P1 2.1590(7), Ni−P2 2.1965(6), Ni−O1 1.922(2), Ni−C1
2.049(2), Ni−C2 1.989(3).
PhCOCF3 )Ni(dppe)1 2 g (3a, dppe
= 1, 2-bis-
(diphenylphosphino)ethane). However, complex 3a led to
decomposition following treatment with 1. Therefore, we
decided to use a more electron-rich bidentate phosphine ligand,
1,2-bis(dicyclohexylphosphino)ethane (DCPE) that would
result in a nickel center that was more suitable for C−F
bond activation by increasing the electron density,13 with a
resultant Ni(II) complex that was more stable. The reaction of
Ni(cod)2 and DCPE with 2a resulted in the formation of (η2-
PhCOCF3)Ni(dcpe) (3b) in an 85% isolated yield. The signal
attributable to the carbonyl carbon in 3b (73.8 ppm) was
observed in the upfield region relative to that of 3a (79.4
ppm).12g This upfield-shift would be invoked by the stronger
electron-donating ability of the DCPE ligand that would
enhance d → π* back-donation. Treatment of 3b with 1 in
C6D6 afforded [(PhCOCF2)Ni(dcpe)][FB(C6F5)3] (4) in a
quantitative yield (Scheme 1). It is noteworthy that in the
The reaction of 4 with tBuNC resulted in the coordination of
isocyanide to the Ni(II) center to give η1-C-enolate 5 in an 87%
yield (Scheme 2). 19F NMR showed a signal derived from CF2
t
Scheme 2. Treatment of BuNC with 4
at δ = −79 ppm (dd, JPF = 22, 30 Hz). In the 31P NMR
spectrum, two signals were observed at δ = 79 (dt, JPP = 29 Hz,
JPF = 22 Hz) and 78 ppm (dt, JPP = 29 Hz, JPF = 30 Hz). The
13C NMR spectrum exhibited a resonance of carbonyl carbon at
δ = 194.1 ppm as a triplet (2JCF = 22.3 Hz). This was
unambiguously supported by X-ray analysis (Figure 3).
Scheme 1. Treatment of 3b with 1 To Yield the Fluorinated
Nickel Enolate 4
absence of 1, complex 3b was thermally stable. In fact, no
decomposition was observed after heating the C6D6 solution of
3b at 100 °C in a sealed NMR tube for a period of several days.
Nickel complex 4 was fully characterized by NMR, elemental
analysis and X-ray crystallography. The 19F NMR spectrum of 4
exhibited a signal that was attributable to CF2 at δ = −100 ppm
(2F, dd, JPF = 7, 18 Hz) and resembled that of previously
reported analogous platinum complex D (Figure 1b)5b as well
as a set of resonances for the [FB(C6F5)3] counteranion.14 In
the 31P NMR spectrum, two sets of doublet of triplets with the
same intensity were observed at δ = 80 (JPF = 7 Hz, JPP = 11
Hz) and 82 ppm (JPF = 18 Hz, JPP = 11 Hz). The presence of
two 31P resonances was probably due to a weak interaction
between the carbonyl oxygen atom and the nickel center
preventing a fluxional rotation around the Ni−C bond.15
Fine crystals of 4 were obtained from the toluene/pentane
layer at −35 °C. The ORTEP diagram of the cationic portion of
4 depicts a fluorinated enolate complex of Ni(II) coordinated
in an η3-oxallyl fashion (Figure 2). The C1−O1 bond length of
1.313(3) Å was an intermediate between a typical C−O double
bond (ca. 1.22 Å) and a single bond (ca. 1.44 Å). The bond
length of the C1−C2 bond of 1.426(5) Å was also within the
range of standard C−C (ca. 1.54 Å) and CC (ca. 1.34 Å)
bond lengths.
Figure 3. ORTEP representation of the cation of 5 with thermal
ellipsoids at the 50% probability level. H atoms and the [FB(C6F5)3]
counteranion were omitted for clarity. Selected bond lengths (Å):
Ni−P1 2.215(2), Ni−P2 2.215(2), Ni−C1 1.966(7), Ni−C3 1.842(9).
The solid-state structure of 5 showed the square-planar
geometry of the Ni(II) C-bound enolate. The observed
C2−O1 bond lengths of 1.219(10) Å and C1−C2 of
1.495(9) Å were typical values of a C−O double bond and a
C−C single bond, respectively.
Transition-metal enolates often act as nucleophiles toward
aldehydes.16 For instance, a C-bound nickel enolate reacted
with an aldehyde to give aldol products according to a report of
Bergman and Heathcock.16a The complex 4 containing
electron-withdrawing fluorine atoms on an enolate moiety
smoothly reacted with 1 equiv of p-tolualdehyde (6a) to allow
B
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the migratory insertion of the carbonyl group into the Ni−C
bond in a quantitative yield (Scheme 3). This was in sharp
structure of 7b was determined by X-ray crystallography to be
consistent with that deduced by NMR spectroscopy (Figure 4).
Scheme 3. Insertion of Aldehyde 6a and 6b into Ni−C Bond
of 4
contrast to the reactions of corresponding silyl enolates with
aldehydes that required the addition of Lewis acids and/or an
excess amount of substrates and suffered from low yields.7,17
We think that the C−C bond formation might occur via the
Zimmerman−Traxler-type six-membered transition-state ini-
tiated by coordination of an aldehyde giving an O-bound
enolate intermediate E (Scheme 4). This is partly supported by
Figure 4. ORTEP representation of the cation of 7b with thermal
ellipsoids at the 30% probability level. H atoms except for H3 and the
[FB(C6F5)3] counteranion were omitted for clarity. Selected bond
lengths (Å): Ni−P1 2.180(2), Ni−P2 2.136(2), Ni−O1 1.932(5), Ni−
O2 1.818(6).
On the other hand, the reaction of 4 with 2 equiv of 6a also
resulted in the formation of 7a and a homocoupled ester 8a,
which was unexpectedly formed from the residual aldehyde
(Scheme 5). The dimerization of aldehydes to give an ester is
Scheme 4. A Possible Reaction Pathway to Give Nickel
Alkoxide Complex 7
Scheme 5. Reaction of 4 with 2 equiv of 6a
́
the report of Campora et al. in which they concluded that only
the O-bound enolate is sufficiently nucleophilic to afford the
aldol product by a reaction with an aldehyde, based on
unequivocal evidence for the difference of the reactivities
between the O-bound Ni(II) enolate and its C-bound
tautomer.16c The reaction, however, was too fast to observe
any intermediates when the reaction of 4 with 6a was
monitored by means of NMR at −50 °C.
known as the Tishchenko reaction, and it is one of the most
famous methods of ester synthesis in an atom-economic and
waste-free reaction manner.18 The classical Tishchenko
reactions catalyzed by aluminum alkoxides, however, suffer
from limited substrate scope. Thus, many catalyst systems have
been developed for this promising reaction avoiding side
reactions such as the aldol reaction, the Cannizzaro reaction,
the Meerwein−Pondorf−Verley reduction, and the Oppenauer
oxidation. Encouraged by our results, we next investigated the
catalytic activity of 4 in a Tishchenko reaction (Table 1).
In the presence of 1 mol % of 4, the reactions of 6a,
benzaldehyde (6c), 4-biphenylcarboxyaldehyde (6d), 3,5-
dimethylbenzaldehyde (6e), and 4-anisaldehyde (6f) afforded
the corresponding esters 8a,c−f in excellent isolated yields
under ambient temperature for 1 h. Contrary to these results, 2-
tolualdehyde (6g) did not react at ambient temperature.
However, the reaction proceeded smoothly by heating at 60 °C
for 1 h to give the corresponding ester 8g in a quantitative
yield. Even very bulky mesitaldehyde (6h) reacted under these
conditions to yield 8h in an 87% yield. Aldehydes bearing either
an ester 6i or an acetal 6j group were tolerated under these
reaction conditions to give 8i and 8j in 98 and 84% yields,
respectively. The reaction of 2-naphthaldehyde (6k) gave the
corresponding ester 8k in a quantitative yield; however, the
reaction of 1-naphthaldehyde (6l) required an elevated
temperature to obtain 8l. The intramolecular Tishchenko
reaction of o-phthalaldehyde (6m) occurred to give phthalide
8m in the presence of 2 mol % of 4, and no oligomer was
observed in the crude reaction mixture. This result was in sharp
contrast with that of our previous report employing a Ni(0)
The 19F NMR spectrum of the resultant complex 7a showed
two signals that could be attributable to a diastereotopic CF2
group at δ = −103 (dd, JHF = 9 Hz, JFF = 270 Hz) and −118
ppm (dd, JHF = 12 Hz, JFF = 270 Hz). Coupling constants of 9
and 12 Hz were attributable to the 3JHF coupling and suggested
a C−C bond formation between an enolate and an aldehyde.
This was consistent with the substantial upfield shift of a signal
1
derived from a formyl group to 4.9 ppm in H NMR that was
observed as a broad triplet with a coupling constant of ca. 10
Hz that resulted from the coupling of two fluorine atoms at 9
2
and 12 Hz. A large coupling constant of 270 Hz for JFF in the
19F NMR is characteristic of geminal coupling between fluorine
atoms bound to sp3 C. In the 31P NMR spectrum, two signals
with equivalent intensities were observed at 88 and 77 ppm and
were coupled at 59 Hz. The two inequivalent phosphorus
atoms indicated coordination of the carbonyl and newly formed
carbinol oxygen atoms to the nickel center. The 13C NMR
spectrum of 7a in CD2Cl2 gave signals attributable to CF2 at
1
118.7 ppm as doublet of doublet bearing characteristic JCF
coupling constants, 251 and 265 Hz, and α-carbons at 202.2 (t,
2
2JCF = 28.5 Hz, carbonyl group) and 73.5 ppm (t, JCF = 23.0
Hz, carbinol carbon). Although we could not obtain a single
crystal of 7a, an analogous complex 7b, generated by the
reaction of 4 with 9-anthracenecarboxaldehyde (6b), was
isolated, and its single crystal was obtained. The molecular
C
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Table 1. Substrate Scope of Homo-Esterification of
Aldehydes
Scheme 6. Treatment of 7a with 2 equiv of 6p
a
alkoxide complex 7a was quite fast even at −50 °C, and
complete conversion of the starting complex 4 was confirmed
by 19F NMR. However, at this temperature, starting aldehyde
6a was observed along with only trace amount of homo-
Tishchenko product 8a. Although the Tishchenko reaction
mostly did not proceed below −10 °C, the broadening of the
signal of the formyl proton of 6a was observed by raising the
temperature.
A possible reaction mechanism is described in Scheme 7.
First, the reaction of 4 with an aldehyde generates the active
Scheme 7. A Possible Reaction Pathway of the Tishchenko
Reaction
a
b
c
Isolated Yields. Reactions conducted at 60 °C. 2 mol % catalyst
d
loading. NMR yield.
catalyst wherein the reaction of 6m yielded a complicated
mixture as a result of oligomerization.19a Not only aromatic
aldehydes but also aliphatic aldehydes such as primary 6n,
secondary 6o and 6p, and tertiary alkylaldehyde 6q were prone
to esterification under the reaction conditions to afford the
corresponding esters 8n−q in good to high yields.
Furthermore, the catalytic transformation of acetaldehyde
(6r) into ethyl acetate (8r) was accomplished in moderate
yield. Complex 4 proved to be an efficient catalyst for the
Tishchenko reaction with utility toward both aromatic and
aliphatic aldehydes and relatively low degree of catalyst
loading.19,20
catalyst 7. Insertion of aldehyde into the nickel alkoxide bond
in 7 then gives intermediate F. The carbonyl group coordinated
to the nickel center in an intermediate F is replaced by another
aldehyde to generate an intermediate G that is transformed into
H by β-hydrogen elimination−insertion sequence. Internal
nucleophilic substitution of ester yields the homocoupling
product with regeneration of the active catalyst 7.
Although the complete reaction mechanism is unclear at this
point, we propose that the nickel alkoxide complex 7 might be
involved as an active catalyst. The reaction of 7a with 2 equiv of
aldehyde 6p resulted in a quantitative formation of
homoesterification product 8p (Scheme 6). Note that ester
products bearing a p-tolyl group derived from 7a were not
detected from the reaction mixture, and complex 7a was
recovered. We also tested the reaction of 7a with 6k-d1 with
formyl proton deuterated to afford the 8k-d2, and no significant
scrambling was observed. This result rules out the possibility of
nickel-hydride species as an active catalyst, although other
metal hydrides often catalyze the Tishchenko reaction. To gain
deeper insight into the mechanism, we monitored the reaction
of 4 with 2 equiv of 6a in toluene-d8 by use of a variable-
temperature NMR from −50 to 25 °C. Formation of a nickel
Next, we attempted the crossed-esterification of a ketone
with an aldehyde (Scheme 8). In the presence of a catalytic
amount of 4, the reaction of acetophenone with 6k gave no
Scheme 8. Crossed-Esterification of Ketones with Aldehyde
6k
D
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coupling product and both starting materials were recovered.
However, reaction of 2a with 6k gave the desired product 9ak
in high yield. The crossed-esterification of 2a with aldehydes
was reported by Connon’s group utilizing thiophenoxide or
selenoxide catalysts.19b,21 The reaction also proceeded with
difluoroacetophenone (2b) to give the corresponding ester
compound 9bk in a 92% yield. The reactions of 4′-methoxy-
2,2,2-trifluoroacetophenone (2c) and 2,2,2,3,3-pentafluoropro-
piophenone (2d) were also successful. Note that no coupling
product derived from nickel catalyst 4, i.e., 9ak, was observed
from these reaction mixtures by GCMS. We also attempted the
reaction with α-fluoroacetophenone, but the starting materials
were recovered from the reaction mixture along with some
unidentified products that were not isolable.
In this crossed-esterification reaction, a nickel alkoxide
complex generated by insertion of a fluorinated ketone 2 to a
fluorinated nickel enolate 4 would be involved as a resting state
of the catalyst. The reaction of 2c with 4 afforded a nickel
alkoxide complex 10 that was characterized by NMR
spectroscopy (Scheme 9). It is noteworthy that the complex
Table 2. Optimization of the Reaction Condition of
Crossed-Esterification of a Trifluoroacetophenone 2 with an
Aldehyde
ab
,
run
catalyst
conditions
yield
1
2
3
4
5
6
7
10 mol %
10 mol %
10 mol %
10 mol %
10 mol %
10 mol %
2 mol %
toluene, 100 °C, 4 h
toluene, 100 °C, 4 h
toluene, 100 °C, 4 h
toluene, 100 °C, 4 h
toluene, 60 °C, 5 h
THF, 60 °C, 5 h
88%
ND
ND
ND
64%
87%
88%
c
d
e
f
THF, 60 °C, 24 h
a
Yields were determined by GC using tetradecane as an internal
b
c
d
e
standard. ND = not detected. Without DCPE. Without 1. Without
Ni(cod)2. Isolated Yield.
f
Scheme 9. Insertion of Ketone 2c into Ni−C Bond of 4
dimethylbenzaldehyde 6q and 3,5-dimethylbenzaldehyde 6e
gave corresponding cross-coupled esters 9aq and 9ae in 84 and
94% yields, respectively. A bulky aldehyde 6h reacted to give
ester 9ah in a high yield using an elongated reaction time. The
reaction of 6d was also successful, and the structure of the
product 9ad was confirmed by X-ray crystallography (Figure 5).
The ester and acetal groups on the aldehydes survived under
these reaction conditions and gave the corresponding esters 9ai
and 9aj. The reaction of p-formylbenzonitrile 6r was
unsuccessful under the optimized conditions listed above, and
the starting materials were recovered. The reaction conducted
in toluene at 100 °C, however, yielded the corresponding ester
9ar in a moderate yield. In the same manner, the reaction of 2a
with 6f afforded a quantitative product 9af in toluene at 100 °C.
Naphthaldehydes 6k and 6l reacted with 2a to give the
corresponding esters 9ak and 9al in THF at 60 °C for 24 h.
Using an aldehyde bearing the phenanthrene structure 6s
required a much longer time to yield the ester product 9as. The
reaction of p-phthalaldehyde with 2 equiv of 2a resulted in the
conversion of both aldehyde moieties to afford diester 11 in a
40% yield. The reactions of 2a with aliphatic aldehydes such as
6n and 6m were unsuccessful in delivering the required
products 9an and 9ap. The reaction of 2a with 6q, however,
gave the corresponding ester 9aq in a 75% yield. Both
trifluoroacetophenone bearing electron-donating methoxy
group 9c and -withdrawing CF3 group 9e reacted cleanly to
give the desired product in high yields. The reaction of
alkylketone 2f with 6k gave no coupling product. Difluorinated
ketone 2b reacted with 6k to give the corresponding ester 9bk
in a good yield. This result implies formation of an active nickel
catalyst from α,α-difluorinated ketone. The reaction of 9d
conducted in THF resulted in a low conversion of starting
materials. Therefore, we attempted the reaction in toluene at an
elevated temperature (100 °C), which afforded the desired
ester 9dk in a 66% yield.
10 showed no catalytic activity for homoesterification of
aldehyde 6a at room temperature, probably because the
insertion of aldehyde to complex 10, a possible step involved
in the homo-Tishchenko reaction, might not occur. The
difference in catalytic activities between alkoxide complexes 10
and 7a might be rationalized by lower nucleophilicity of 10
bearing a highly electron-withdrawing CF3 group than that of
complex 7a. To gain further insight, we monitored the reaction
of 2a with 6k in the presence of catalytic amount of 4 by use of
variable-temperature NMR at 95 °C (Figure S1). As a result,
interestingly, we observed an induction period that indicates
formation of an active catalyst from nickel alkoxide species
under the reaction condition. Mechanistic studies to elucidate
this phenomenon are ongoing.
These results motivated us to develop a more practical
catalyst system for the crossed-esterification of a trifluorome-
thylketone with an aldehyde in which an active nickel catalyst
was generated in situ from the reaction of Ni(0),
trifluoromethylketone 2, and 1. In the presence of 10 mol %
of Ni(cod)2, DCPE, and 1, the reaction of 2a with 6a in toluene
at 100 °C resulted in the formation of the corresponding cross-
coupled ester 9aa in an 88% yield (Table 2, run 1). The
reaction did not work in the absence of Ni(cod)2, DCPE, or 2
(runs 2−4). Reactions with other ligands (1,2-bis-
( d i p h e n y l p h o s p h i n o ) e t h a n e a n d 1 , 3 - b i s ( 2 , 6 -
diisopropylphenyl)imidazole-2-ylidene as well as 20 mol % of
PCy3) gave no coupling product. The use of THF as a solvent
allowed the reaction to proceed at a temperature that was lower
than that of the reaction conducted in toluene (runs 5, 6). The
amount of catalyst loadings could be reduced to 2 mol %, and
with this optimized condition, the desired product was
successfully isolated in an 88% yield (run 7).
CONCLUSION
■
In summary, we have demonstrated the first synthesis of a
fluorinated analogue of nickel enolate 4, via the C−F bond
activation of trifluoroacetophenone, which was drastically
accelerated by the addition of B(C6F5)3. The combination of
Ni(0) with an electron-rich DCPE ligand might be the key to
With the optimized reaction conditions in hand, substrate
scope was studied (Table 3). The reactions of 2a with 2,4-
E
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the in situ generation of a nickel-enolate catalyst. Thus, we have
successfully developed an efficient Ni(cod)2/DCPE/B(C6F5)3
catalyst system for a highly selective crossed-esterification of
trifluoroacetophenones with aldehydes. Detailed studies on the
reaction mechanism of esterification are currently underway in
our laboratory.
Table 3. Substrate Scope of Crossed-Esterification of
Trifluoroacetophenone 2 with Aldehydes 6 by Using in Situ-
a
Generated Catalyst
ASSOCIATED CONTENT
* Supporting Information
■
S
Experimental details of isolation and characterization of all the
new compounds are described along with spectral data. This
material is available free of charge via the Internet at http://
pubs.acs.org.
AUTHOR INFORMATION
Corresponding Authors
*ogoshi@chem.eng.osaka-u.ac.jp
*ohashi@chem.eng.osaka-u.ac.jp
■
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was partially supported by a Grant-in-Aid for Young
Scientist (A) (25708018) and a Grant-in-Aid for Scientific
Research on Innovative Areas “Molecular Activation Directed
toward Straightforward Synthesis” (23105546) from MEXT
and by the ACT-C and the A-STEP programs from JST. R.D. is
grateful for support as a JSPS Research Fellow. M.O. also
acknowledges The Noguchi Institute.
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a
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Isolated Yields. ND = not detected. 50 h. Reactions conducted at
d
100 °C in toluene. Reactions conducted at 100 °C in toluene for 48
h. 4 mol % catalyst loading.
e
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t
3 with BuNC resulted in coordination to the nickel center to
́
(c) Hratchian, H. P.; Chowdhury, S. K.; Gutierrez-García, V. M.;
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F
DOI: 10.1021/ja511730k
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Journal of the American Chemical Society
Article
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(15) We failed to find resonances derived from carbonyl and CF2
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upfield shift of resonance of carbonyl carbon caused by the interaction
G
DOI: 10.1021/ja511730k
J. Am. Chem. Soc. XXXX, XXX, XXX−XXX