Metal Heptafluoroisopropyl (M-hfip) Complexes for Use as hfip Transfer Agents

Article abstract of DOI:10.1021/acs.organomet.7b00837

New coinage-metal heptafluoroisopropyl (L_nM-hfip) complexes are synthesized from the metal fluoride and inexpensive hexafluoropropene (M = Ag, Cu; L = PPh₃, 2,2,6,6-tetramethylpiperidine (Htmp)). Reaction of the silver Htmp complex with a Ni dibromide complex led to efficient hfip transfer to afford L₂NiBr(hfip) (L = 2-ethylpyridine). Treatment of the Ni-hfip complex with ZnPh₂ gave the corresponding L₂NiPh(hfip) complexes, which were investigated for reductive elimination of PhCF(CF₃)₂. Although the desired reductive elimination proved unsuccessful, addition of carbon monoxide to L₂NiPh(hfip) effected an efficient heptafluoroisopropyl carbonylative cross-coupling. Further, while the silver complex does not undergo hfip transfer to organic electrophiles, the copper complex (phen)(PPh₃)Cu(hfip) (3b) effectively transfers the hfip unit to various substrates. We investigated the scope of 3b with acid chlorides toward the synthesis of perfluoroisopropyl aryl ketones. Additionally, reaction conditions for hfip transfer to p-fluorobenzyl bromide and p-fluorobenzaldehyde were identified. As a bonus, 3b was easily generated on a gram scale using commercially available copper hydride by taking advantage of a rapid hydrodefluorination to generate Cu-F in situ. Aspects of the observed reactivity are supported by DFT calculations.

Full text of DOI:10.1021/acs.organomet.7b00837

Article
Cite This: Organometallics XXXX, XXX, XXX−XXX
Metal Heptafluoroisopropyl (M-hfip) Complexes for Use as hfip
Transfer Agents
Nicholas O. Andrella,† Karen Liu,† Bulat Gabidullin,† Monica Vasiliu,‡ David A. Dixon,‡
and R. Tom Baker*,†
†Department of Chemistry and Biomolecular Sciences and Center for Catalysis Research and Innovation, University of Ottawa,
Ottawa, Ontario K1N 6N5, Canada
‡Department of Chemistry, The University of Alabama, Tuscaloosa, Alabama 35487, United States
S
* Supporting Information
ABSTRACT: New coinage-metal heptafluoroisopropyl (LnM-
hfip) complexes are synthesized from the metal fluoride and
inexpensive hexafluoropropene (M = Ag, Cu; L = PPh3, 2,2,6,6-
tetramethylpiperidine (Htmp)). Reaction of the silver Htmp
complex with a Ni dibromide complex led to efficient hfip transfer
to afford L2NiBr(hfip) (L = 2-ethylpyridine). Treatment of the Ni-
hfip complex with ZnPh2 gave the corresponding L2NiPh(hfip)
complexes, which were investigated for reductive elimination of
PhCF(CF3)2. Although the desired reductive elimination proved
unsuccessful, addition of carbon monoxide to L2NiPh(hfip)
effected an efficient heptafluoroisopropyl carbonylative cross-
coupling. Further, while the silver complex does not undergo hfip transfer to organic electrophiles, the copper complex
(phen)(PPh3)Cu(hfip) (3b) effectively transfers the hfip unit to various substrates. We investigated the scope of 3b with acid
chlorides toward the synthesis of perfluoroisopropyl aryl ketones. Additionally, reaction conditions for hfip transfer to p-
fluorobenzyl bromide and p-fluorobenzaldehyde were identified. As a bonus, 3b was easily generated on a gram scale using
commercially available copper hydride by taking advantage of a rapid hydrodefluorination to generate “Cu−F” in situ. Aspects of
the observed reactivity are supported by DFT calculations.
INTRODUCTION
■
Fluorinated carbon fragments, i.e. fluoroalkyls and -aryls, have
become quite common in many applications.1,2 In the
pharmaceutical industry,3,4 for example, many household
drugs now contain these functional groups,5 which offer
benefits in metabolic stability, solubility, lipophilicity, and
bioavailability. Many of these fluoroalkyl-containing drugs have
Figure 1. Biologically active compounds containing hfip group.
become “blockbusters”, such as Celebrex, Prevacid, and
Pantoprazole.
While many such fragments can be envisioned, only a few are
currently readily accessible. For example, trifluoromethylation
The Ruppert−Prakash reagent Me3Si-CF3, for example, has
seen widespread adoption primarily because of its moderate
cost and ready availability.12 Recently, Grushin et al.
successfully prepared a series of [Cu]CF2CF3 complexes
reactions have seen a period of rapid growth spurred by unique
biological applications.6 However, installation of other fluo-
10
roalkyl fragments such as CF2H,7 C2F5,8 OCF3,9 and SCF3
remains challenging. There has also been a huge investment in
identifying new biologically active agents for use in both the
agrochemical and pharmaceutical industries. For example, the
heptafluoroisopropyl (hfip) group has recently been incorpo-
rated into insecticides (Figure 1),11 prompting our current
study of its synthesis, coordination chemistry, and transfer to
organic electrophiles.
generated from pentafluoroethane,13 and Vicic et al. developed
a zinc reagent of the type [Zn]CF2H.14 In both cases, the cost
of preparation for these reagents remains low by using base
metals and readily available hydrofluoroalkanes. The reactivity
of these reagents depends heavily on the choice of ancillary
ligand, with 1,10-phenanthroline (phen) giving rise to increased
reactivitysuch as the (phen)Cu(CF3) Trifluoromethylator.15
In this report, we find that changes in the coordination
The success and application of fluoroalkylation routes
generally hinges on the stability and ease of access of the
critical reagent.
Received: November 20, 2017
© XXXX American Chemical Society
A
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chemistry of copper leads to improved transfer of the hfip
fragment to organic electrophiles.
Scheme 2. Reported Reactions of hfip Compounds
To date, methodologies for the introduction of the hfip
group to organic molecules remain scarce. One can generate
the hfip nucleophile as the hfip anion [CF(CF3)2]− (Figure
2A)16 or the metal complex [M]-hfip (Figure 2B).17 In these
Figure 2. Heptafluoroisopropyl anion vs M-hfip complex.
procedures, two reagents provide a foundation to access the
hfip moiety. The more obvious of the two is 2-iodohepta-
fluoropropane, which has been successfully metalated to yield
hfip complexes (Scheme 1A)18 Alternatively, one can generate
Scheme 1. (A) Metalation of Heptafluoro-2-iodopropane
and (B) Addition of M−F to Hexafluoropropene
Scheme 3. Synthesis of Compound 1
similar compounds from hexafluoropropene (HFP) and a
source of fluoride (Scheme 1B).19 This route benefits from the
significantly less expensive starting material (23.7 (HFP) vs 192
$/mol (Ihfip)), and HFP can be generated selectively from
waste polytetrafluoroethylene (PTFE).20
In reports that explore such reactivity, four reagents stand
out: the hfip anion and hfip complexes of cadmium, silver, and
copper (Scheme 2).21 Evidently, each system has its own
drawbacks, which could possibly be remediated with the
development of new hfip organometalllic reagents. Herein, we
report the synthesis and characterization of new Cu, Ni, and Ag
hfip complexes. The reactivity of each compound is then tested
with simple organic electrophiles to determine the nucleophil-
icity.
progressively grayer over time. However, this did not preclude
the collection of single-crystal X-ray diffraction data (Figure 3).
Figure 3. ORTEP representation of the molecular structure of 1.
Thermal ellipsoid probabilities are set to 35%, with hydrogen atoms
omitted for clarity.
RESULTS AND DISCUSSION
■
Synthesis and Characterization of a Silver hfip
Complex. Following a modified literature procedure,19a the
new silver hfip complex 1 was prepared directly from HFP and
silver fluoride in the presence of 2,2,6,6-tetramethylpiperidine
(Htmp) (Scheme 3). As is typical for such reactions, only a
single isomer is observed. The metal fluoride inserts HFP such
that the less sterically hindered and the more δ+ carbon (
CF2) is oriented toward the fluoride. This choice of ligand was
inspired by previous work with AgCF3 complexes,22 to target
the neutral compound (vs [Ag(CF3)2]−). The colorless powder
1 is slightly unstable at room temperature, becoming
The molecular structure of complex 1 exhibits a linear
coordination about Ag and features a hydrogen bond
interaction (N−H···F) between the isopropyl fluoride (F4)
and the tetramethylpiperidine amine (N1H1′) from the
neighboring complex in the crystal lattice (see Figure S40 in the
Supporting Information). There is a slight distortion from
linearity with the shortest C12−Ag−N1 angle being 173°.
B
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The 19F NMR spectrum of 1 in C6D6 is consistent with the
structure determined in the solid state. Whereas the
trifluoromethyl group displays a chemical shift difference for
the 106Ag and 107Ag isotopomers, the iPr fluoride does not and
neither resonance displays Ag−F coupling. Consistent with
previous reports, on dissolution in more polar and coordinating
solvents an equilibrium between (Htmp)Ag[CF(CF3)2] and
Ag+[Ag{CF(CF3)2}2]− is evident, with the neutral complex
being favored.17g
Synthesis and Characterization of Nickel hfip Com-
plexes. With the stable Ag complex 1 in hand, we proceeded
to transmetalate the hfip fragment to other transition-metal
halides.23 Generally, the reaction with transition-metal halides
led to decomposition of 1 by formation of HFP (β-fluoride
elimination) or 2H-heptafluoropropane. Reaction with bis(2-
ethylpyridine)nickel dibromide in benzene, however, yielded
the singly transmetalated product 2a (Scheme 4). Even when
an excess of 1 was used, only 2a was observed.
to the CH2Et and CHpy fragments which reside closest to the
metal center. The dynamic process that contributes to these
broad resonances is most evident in the variable-temperature
19F NMR spectrum that exhibits the expected doublet and
septet resonances only at elevated temperature (Figure S8). At
room temperature the inequivalent CF3 resonances are likely
due to hindered rotation about the Ni−C and Ni−N bonds in
the two rotamers observed in the solid-state structure.
As 2a can be considered the oxidative addition product of Br-
CF(CF3)2 to nickel(0), it may serve as a potential platform to
study the cross-coupling synthesis of Ar-CF(CF3)2. To model
such a reaction, we selected diphenylzinc as a potential coupling
partner. Immediately upon addition of the zinc reagent to a
solution of 2a in THF, a reaction was observed to form
complex 2b (Scheme 5). This new complex (not isolated) was
Scheme 5. Synthesis of Phenyl Ni-hfip Complexes 2b−d
Scheme 4. Synthesis of Compound 2a
The nickel atom of complex 2a adopts a square-planar
geometry with the hfip and bromide trans to each other (Figure
4). While the Cα−F bond appears to be significantly longer24
then treated in situ with bis(phosphines) to give stable
products: 1,2-bis(dicyclohexylphosphino)ethane (dcpe; 2c),
1,1′-bis(diphenylphosphino)ferrocene (dppf; 2d (not iso-
lated)), and xantphos (multiple products).
Complex 2c was isolated as a bright yellow powder and
crystallized from acetonitrile. The molecular structure of 2c
shows a distorted-square-planar Ni center with the hfip and the
phenyl cis to each other (see Figure S1 in the Supporting
Information). The Cα−F bond distance (1.437 Å) is now closer
in length to that in complex 1.
Synthesis and Characterization of Copper hfip
Complexes. Reaction of 1 with copper chloride in benzene
produces the solvated Cu-hfip complex disclosed previously17c
and used extensively in arylboronic acid cross-coupling
reactions21a and others.18b,21 Looking to avoid the use of the
costlier silver fluoride starting material (928 $/mol), we
endeavored to synthesize the Cu complex from commercially
available copper fluoride dihydrate (43 $/mol) and triphenyl-
phosphine (45$/3 mol). The choice of copper fluorides is
limited, since only a few have been reported and/or isolated,25
with (PPh3)3CuF being successfully used as a source of
Figure 4. ORTEP representation of the disordered molecular structure
of 2a (ethyl groups can be syn, anti or anti, anti to hfip). Thermal
ellipsoid probabilities are set to 35%, with hydrogen atoms omitted for
clarity.
than that in 1 (1.59 Å (average) vs 1.420(2) Å in 1), this is
likely an artifact of the disorder in the crystal structure, as the
calculated value is in line with other complexes (Table 1).
The 1H NMR spectrum of 2a has three broad signals
centered at δ 4.5, 5.2, and 9.4, respectively. These are assigned
a
Table 1. Selected Bond Lengths
1
2a
2c
3a
3b
́
nucleophilic fluoride. In one example, Szabo et al. demon-
M−C
Cα−F
Cβ−F
2.11/2.14
1.42/1.42
1.32/1.36
2.00/2.04
2.00
1.44
1.35
2.00/2.04
1.43/1.43
1.35/1.37
2.00/2.04
1.44/1.43
1.34/1.37
c
strated the substitution of allylic C−X bonds (X = Br, Cl, OTf)
using said reagent to synthesize allylic C−F compounds.26
Similarly, Grushin et al. employed this complex to easily
generate CuCF3 from Me3SiCF3.27 In this regard, we expected
the coinage-metal fluoride to yield a net addition of Cu−F
across the HFP double bond, as seen with AgF.
1.60 /1.42
b
1.35/1.36
a
All values are rounded and are given in Å: experimental/calculated.
Average for calculated values at the DFT/B3LYP level. Accuracy
likely affected by disorder.
b
c
C
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The copper(I) fluoride complex CuF(PPh3)3 was synthe-
sized as previously reported,24a and treatment with HFP in
Et2O over a 24 h period afforded the hfip complex 3a in high
yield (80%) and excellent purity (>90%, Scheme 6). Solvents of
Scheme 7. Synthesis of 3a from HFP and Stryker’s Reagent
Scheme 6. Synthesis of 3a from HFP and Copper(I)
Fluoride
on the Cu−C or Cα−F bond lengths (Figure 5 (right) and
Table 1).
higher polarity yielded impurities that are not trivially separated
from 3a. Moreover, the use of dichloromethane or N,N-
dimethylformamide (DMF) yielded no product and only HFP
oligomers. Like the previously reported pentafluoroethyl
copper complex,28 the molecular structure of 3a features a
hfip group and two PPh3 ligands in a trigonal-planar array about
the copper (Figure 5 (left)). As expected, the Cu−C bond
The 19F NMR spectrum of 3a in C6D6 shows an unusually
broad resonance for Cα−F, indicating some fluxional behavior.
This is supported by a broad signal in the 31P NMR spectrum at
−5 ppm for both PPh3 ligands. While 3b in C6D6 reveals a
similar trend in the 31P NMR spectrum (broad resonance at −5
ppm), the 19F NMR spectrum now consists of sharp resonances
3
with the typical JFF coupling constant (FC−CF3) being quite
1
apparent, although no JPF value could be identified. The H
NMR spectrum also shows broadening of the signal assigned to
phen-H lying closest to the metal center, resulting presumably
from fast cleavage and re-formation of the Cu−PPh3 bond.
Reactivity of M-hfip Complexes with Aroyl Chlorides.
Having these four new M-hfip complexes in hand, we
proceeded to test their reactivity with benzoyl chloride to
determine which one may be a suitable platform for further
nucleophilic studies. First, when 1 was mixed with benzoyl
chloride in many solvents, no reaction was observed. This is in
line with previously described reactivity for the analogous
compound (MeCN)Ag[CF(CF3)2].17h Second, when 2a was
mixed with benzoyl chloride, immediate formation of HCF-
(CF3)2 (Hhfip) was observed. In contrast, when 3a or 3b was
mixed with benzoyl chloride in DMF, both produced
fluorinated ketone 4a in moderate (50%) and high (75%)
yields, respectively. In the case of 3a the reagent is unstable
under the reaction conditions and produces an equivalent
amount of benzoyl fluoride, arising presumably from β-fluoride
elimination with concomitant formation of HFP. Optimizing
the reaction of 3b with benzoyl chloride, we found that DMF
was required; all other solvents tested yielded no product and
gave exclusively Hhfip. The reaction proceeds readily at room
temperature over 24 h.
Existing methods for the synthesis of these compounds have
been limited either by (a) generation of the [CF(CF3)2]− anion
and accompanying HFP oligomers16a or (b) the use of acid
fluorides, generated from acid chlorides.17i,31 The reaction can
be applied to a wide range of acid chlorides bearing various
functional groups, including halide (4e−g), CN (4i), ether
(4k), alkyl (4c), nitro (4j,k), naphthyl (4l), and thiophene (4n;
Scheme 8). Some steric effects could be observed. For example,
the ortho derivatives gave lower yields (4d,k). The extent of
this effect is better measured using the 2,4,6-chloro-substituted
benzoyl chloride that does not react with 3b. In general, the
electron-rich aroyl chlorides always gave lower yields,
presumably due to reversibility under the reaction conditions.
This is more evident in the case of 3,4,5-trimethoxybenzoyl
chloride, for which the yield drops off as the reaction
progresses. Similarly, this highlights the inherent difficulty in
isolating these products, as the hfip group is readily substituted
and therefore demands rigorously dry conditions. To
Figure 5. ORTEP representation of the molecular structures of (left)
3a and (right) 3b. Thermal ellipsoid probabilities are set to 35%, with
hydrogen atoms omitted for clarity.
(2.003(3) Å) is shorter than the Ag−C bond (2.114(2) Å) but
is like those in the Cu−CF2CF3 (1.99 Å) and Cu−CF3
(2.025(7) Å) analogues. On this note, the Cα−F bond distance
gets progressively smaller with decreasing fluoroalkyl size (1.44
Å for 3a vs 1.40 and 1.39 Å for CF2CF3 and CF3, respectively).
As the reaction to form 3a was slowlikely related to the
limited solubility of [(PPh3)3CuF] in Et2Owe sought an
alternate Cu−X precursor that upon rapid insertion of HFP
would undergo β-fluoride elimination to Cu−F followed by
subsequent addition of HFP to yield 3a. For example, Ogoshi
et al. have taken advantage of β-fluoride elimination of a copper
complex to generate fluorostyrenes.29 To avoid side reactions,
we selected X such that the produced fluoroalkene would be a
gas at room temperature. We thus turned to commercially
available [(PPh3)CuH]6 (Stryker’s reagent). Although copper
hydride has been used for hydrodefluorination of ArF
compounds,30 it has never been used with fluoroalkenes.
When [(PPh3)CuH]6 with an additional 1 equiv of PPh3 per
Cu is exposed to HFP in benzene, it reacts in <2 h to give 3a in
excellent yield (81% based on [(PPh3)CuH]6, Scheme 7).
Moreover, addition of phen to 3a in Et2O gave [(phen)-
(PPh3)Cu(hfip)] (3b) in high yield (>80% based on
(PPh3)2Cu(hfip)) as a bright orange powder. This change in
coordination number and ligand did not have a profound effect
D
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c
Scheme 8. Perfluoroisopropylation of Aroyl Chlorides
Scheme 9. Reactions of 3b with Other Electrophiles
Scheme 10. Reaction of 3b with a Benzyl Bromide and
Suspected Decomposition Pathways of 3b′
a
b
c
1 equiv of 3b. 4 h at room temperature. Reaction conditions unless
specified otherwise: 0.074 mmol of Cu, 0.049 mmol of acid chloride.
and 0.027 mmol of internal standard in 0.5 mL of DMF at room
temperature for 24 h. The reactions were performed in an NMR tube
sealed with a plastic cap and wrapped with Parafilm without stirring.
The yields were determined by 19F NMR spectroscopy with
hexafluorobenzene as an internal standard vs moles of electrophile.
For details see the Supporting Information.
by employing a weak Lewis acid as an additive. While 3b does
not react readily with 4-fluorobenzaldehyde, addition of a
strong Lewis acid also does not produce the desired product.
3b itself reacts with both trimethylsilyl trifluoromethanesulfo-
nate (TMSOTf) and trifluoroborane etherate (BF3·Et2O).
However, addition of triphenylborane gave the desired product
5b in 91% yield.
Reactivity of Ni(Ph)hfip (2b) toward Reductive
Elimination. Upon heating complexes 2b−d to 66 °C, (a)
no reaction (2c), (b) decomposition to Hhfip (2b), or (c) a
mixture of unknown products (2d) was observed. With the
stable complex 2c in hand, we attempted to effect the
associatively induced reductive elimination by addition of
excess triethyl phosphite, 2,6-dimethylphenyl isocyanide, or CO
gas. Although addition of triethyl phosphite had no effect, the
isocyanide reacted immediately to give a mixture of unidentified
products. Addition of CO (3 atm) to 2c (in either THF or
benzene-d6) at 50 °C instead produced the ketone in 90% yield
(Scheme 11), with some Hhfip produced in a side reaction.
compound this issue, all of the products are volatile and could
not be easily separated from DMF. However, they can be
collected as the distillate with DMF.32 Noticeably, phenyl acetyl
chloride, the only alkyl acid chloride, does not react with 3b.
Reactivity of Cu-hfip Complexes with Other Electro-
philes. Reactions of 3b with several other electrophiles
generally required ∼1.5 equiv of 3b due to competing
formation of Hhfip.33 Reaction of 3b with 4-fluorobenzyl
bromide (Scheme 9, top) gave an unusually low yield and
produced several unidentifiable products on heating to 50 °C.
To compound the issue, the product 5a was unstable under
regular workup conditions. In one attempt at isolation of 5a by
column chromatography, no product was collected. Although
we expected the formation of benzyl fluoride to arise from β-
fluoride transfer, we did not observe concomitant formation of
HFP under the reaction conditions.
We suspect that the benzyl fluoride arises from α-fluoride
transfer (Scheme 10, route B) from an intermediate copper(III)
complex (3b′) and is in competition with product formation,
corroborating the 30% yield. On the trend of alkyl halides, we
found that those vicinal to a ketone do not react with 3a (e.g.,
bromoacetophenone). We also found that bulkier benzhydryl
halides do not substitute readily. Unfortunately, 5c was not
stable under the reaction conditions and slowly decomposed,
precluding its isolation. Finally, aldehydes could be substituted
Scheme 11. Carbonylation and Reductive Elimination of the
hfip Group
E
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Table 2. Bond Dissociation Energies (BDE, ΔH0K, and ΔG298 K at the B3LYP/DZVP2/aug-cc-pvdz-pp(M) Level in kcal/mol)
and Charge Distribution of Some Reported Complexes
a
The Ni cation has a triplet ground state.
This suggests that catalytic perfluoroalkylcarbonylation34
using nickel could be possible and will be explored further in
due course.
the perfluoroisopropyl anion. The BDEs for 2a suggest that
both heterolytic and homolytic cleavage could occur.
Computational Chemistry. To provide insight into these
reactivity trends, we carried out DFT calculations (at the
B3LYP/DZVP2/aug-cc-pvdz-pp(M) level; Table 2). The
calculated bond distances are in good agreement with
experiment (Table 1). The calculated 31P gas-phase NMR
chemical shifts are within about 12 ppm of experiment, while
CONCLUSIONS
■
In summary, we have prepared a series of stable M-hfip
complexes and investigated their reactivity. Isolation of the first
stable Ni-hfip complexes demonstrates their potential for new
cross-coupling reactions. The synthesis of 2a was enabled by
the underexploited salt metathesis reaction between Ag-RF and
transition-metal halides, whereby previous attempts had yielded
ionic species such as [Rh]+[Ag(RF)2]−,17f the prior paradigm
being that only copper complexes could be synthesized.17b,21a
Further, this may enable access to metals in low oxidation states
without the need for reduction. However, as demonstrated
herein, a judicious choice of transition-metal starting material
and ligand is necessary for success of these transfers.
Although the aforementioned reaction does yield the copper
complex, we have discovered a new convenient synthesis of Cu-
hfip complexes 3a,b. An easily prepared, air-stable copper
fluoride can be used to synthesize new Cu-hfip complexes, thus
bypassing the need for silver. We have optimized these
conditions to prevent side reactions, such as HFP oligomeriza-
tion, which we found can occur in media other than Et2O. Still,
we wished to improve the reaction efficiency by decreasing the
reaction time (likely limited by poor solubility of the Cu−F
complex) and increasing the atom efficiency (Cu−F synthesis
<50%). We have thus shown that a commercially available
copper hydride can readily hydrodefluorinate HFP, generating
Cu−F in situ which reacts rapidly with HFP to give the Cu-hfip
complex.
those for 19F differ by ∼20−30 ppm for CF3 PrF and the CFiPrF
i
(see the Supporting Information). This is typical of the usual
errors in calculated chemical shifts for these nuclei.
There are two types of bond dissociation energies (BDEs) to
consider for this system: homolytic with formation of a metal-
centered radical and the perfluoroisopropyl radical and
heterolytic with formation of a metal-centered cation and the
perfluoroisopropyl anion. In the gas phase, homolytic cleavage
always requires less energy than heterolytic cleavage. However,
in solution, heterolytic cleavage can become favored due to
solvation of the ions. In the gas phase, 1 and 3a have
significantly higher homolytic BDEs than do 2a and 3b, with 2a
having the lowest homolytic BDE. In DMF solution 3a is
predicted to have a heterolytic BDE of close to 0 kcal/mol and
2a is predicted to have a heterolytic BDE of just above 10 kcal/
mol. In contrast, 1 and 3b have heterolytic BDEs of slightly
greater than 30 kcal/mol in solution. The difference between
the heterolytic BDEs in 3a and 3b arises from the bulky cation
generated from 3b, which is not as well solvated as is the
smaller cation generated from 3a. Furthermore, the perfluor-
oisopropyl anion can release fluoride to generate CF3(F)C
CF2. The fluoride affinity of perfluoropropene is ΔH298 K = 46.3
kcal/mol and ΔG298 K = 37.2 kcal/mol in the gas phase at the
G3MP2 level35 (see the Supporting Information). Inclusion of
a solvent effect leads to the result that it is exothermic to release
On evaluating the reactivity of all new M-hfip complexes
toward electrophiles, we showed that Cu complexes 3a,b
readily transfer the hfip fragment to benzoyl chloride. These
findings have been supported by DFT calculations, which
yielded parameters against which to compare for suspected
reactivity/stability trends. It may serve as a preliminary
screening mechanism to identify successful candidates to
further expand the scope of hfip transfers.
i
F− from the PrF anion by −6.3 kcal/mol.
The lack of reactivity observed for 1 is consistent with the
calculated BDEs. The instability of 3a is also consistent with the
low energy for heterolytic cleavage and should be very sensitive
to reaction conditions, especially as F− can be generated from
F
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was stirred at 25 °C for ∼24 h and wrapped in tin foil. The solid
became dark green after a few hours. As the reaction progressed, the
solution became progressively clear with a slight silver mirror forming.
The solution was filtered through a Celite pad (15 mL medium pore
fritted funnel), and the remaining solvent was removed in vacuo to
yield a colorless powder. A 10 mL portion of hexanes was added, and
the solid was collected (30 mL medium pore fritted funnel), washed
with hexanes (4 °C, 3 × 5 mL), and dried in vacuo to yield 1.44 g of 1
(3.55 mmol, 90% based on AgF). The isolated material was stored in a
refrigerator under nitrogen in an amber container. 1H NMR (300
MHz, C6D6): δ 1.17 (br, 2H, CH2), 1.06 (m, JHH = 6 Hz, 4H, CH2),
The trend in BDE explains quite readily the propensity for
the formation of Hhfip or HFP over the course of the reaction.
This is especially true in the case of 3b, where without judicious
choice of solvent (e.g., DMF) the desired reaction does not
occur, although a balance must be struck between the M−C
BDE (3b ≪ 3a) and the desired reactivity. As a bonus 3b also
possesses a greater positive charge at Cu that could be
beneficial for reactivity with less activated substrates.
Ongoing work is focused on (a) expanding the range of
electrophiles that can undergo substitution with 3b and (b)
exploring conditions for catalytic cross-coupling for both 2c and
3b or analogues thereof. Preliminary results of the stoichio-
metric substitution reactions with 3b are encouraging and
indicate an enhanced reactivity of said reagent. Full details of
these results will be published in due course.
0.76 (br, 12H, Me). 19F NMR (282 MHz, C6D6): δ −68.45 (d, 3JFF
=
3
13 Hz, 6F, CF3), −68.50 (d, JFF = 13 Hz, 6F, CF3), −211.03 (d
“hept”, JFF = 13 Hz, JAgF = 2 Hz, 1F, CFiPrF), −211.12 (d “hept” ,
3
2
3JFF = 13 Hz, JAgF = 2 Hz, 1F, CFiPrF). 13C{1H} NMR (75 MHz,
2
C6D6): δ 17.3 (Htmp), 32.0 (br, Htmp), 37.3 (Htmp), 54.0 (Htmp),
1
2
104.1 (“multiplet”, CFiPrF), 127.1 (qdqd, JCF = 273 Hz, JCF= 24 Hz,
3JCF = 2JAgC = 5 Hz). IR: 3262(w), 2948(w, br), 1452(m, br), 1394(s),
1351(s), 1098(w), 932(s), 734(s), 692(s) cm−1. ESI-MS: m/z (%)
562.15 (100), 563.16 (20), 564.15 (95), 566.15 (15) [M+ − H +
2THF], 142.16 [L+ − H]. See Figures S2−S4 for 1H, 19F, and 13C{1H}
NMR spectra.
EXPERIMENTAL SECTION
■
General Procedures. Experiments were conducted under nitro-
gen, using Schlenk techniques or an MBraun glovebox. All solvents
were deoxygenated by purging with nitrogen. Hexanes, diethyl ether
(Et2O), 1,2-dimethoxyethane (DME), and tetrahydrofuran (THF)
were dried on columns of activated alumina using a J. C. Meyer
(formerly Glass Contour) solvent purification system. Benzene-d6
(C6D6) was dried by stirring over activated alumina (ca. 10 wt %)
overnight, followed by filtration. All solvents were stored over
activated (heated at ca. 250 °C for >10 h under vacuum) 4 Å
molecular sieves, and glassware was oven-dried at 120 °C for >2 h.
The following chemicals were obtained commercially, as indicated:
silver fluoride (AgF, Alfa, 99%), hexafluoropropene (HFP, Synquest,
99%), triphenylphosphine (PPh3, Oakwood Chemical, 99%), copper-
(II) fluoride dihydrate (CuF2·2H2O, Alfa), diphenylzinc (ZnPh2,
Strem Chemicals, 99%), all acid chlorides (Sigma-Aldrich, 99%), 4-
fluorobenzyl bromide (Oakwood Chemicals, 99%), 4-fluorobenzalde-
hyde (Oakwood Chemicals, 99%), 3-bromo-1-phenyl-1-propene
(cinnamyl bromide, Sigma-Aldrich, 97%), 2,2,6,6-tetramethylpiper-
idine (Htmp, Sigma-Aldrich, 99%), 1,10-phenanthroline, anhydrous
(phen, Alfa, 99%), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene
(xantphos, Accela, 97%), 1,1′-bis(diphenylphosphino)ferrocene (dppf,
Accela, 95%), 1,2-bis(dicyclohexylphosphino)ethane (dcpe, Strem,
98%), triethyl phosphite (P(OEt)3, Sigma-Aldrich, 99%), and 2,6-
dimethylphenyl isocyanide (XylCN, Sigma-Aldrich, 96%). 1H, 19F,
31P{1H}, and 13C{1H} NMR spectra were recorded on a 300 MHz
Bruker Avance instrument at room temperature (21−23 °C) unless
Synthesis of [(PyEt)2NiBr(hfip)] (2a). The purple complex
[(PyEt)2NiBr2]59 (1.000 g, 2.31 mmol) was placed in a 100 mL
round-bottom flask and mixed with 30 mL of benzene. A 10 mL
colorless solution of 1 in benzene (990 mg, 2.37 mmol) was then
added to the slurry. The reaction mixture was stirred at 25 °C for 24 h.
The solution became progressively pink as the reaction progressed.
The deep pink solution with a light yellow precipitate (AgBr) was
filtered through a Celite pad (15 mL medium-pore fritted funnel), and
the remaining solvent was removed in vacuo to yield a light pink
powder. Roughly 5 mL of hexanes was added, and the solid was
collected (30 mL medium-pore fritted funnel), washed with hexanes
(4 °C, 3 × 5 mL), and dried in vacuo to yield 1.05 g of 2a (2.00 mmol,
87% based on [(PyEt)2NiBr2]). The isolated material was stored at
room temperature under nitrogen. UV−vis (1.0 mM in THF): λmax
1
(ε) 495 nm (407 M−1 cm−1). H NMR (300 MHz, C6D6): δ 1.38 (t,
3JHH = 7 Hz, 6H, MeEt), 4.56 (br, 2H, CH2Et), 5.19 (br, 2H, CH2Et),
6.23 (td, 3JHH = 7 Hz, 4JHH = 1 Hz, 2H, CHPy), 6.36 (d, 3JHH = 7 Hz,
2H, CHPy), 6.54 (td, 3JHH = 7 Hz, 4JHH = 1 Hz, 2H, CHPy), 9.37 (br,
i
2H, CHPy). 19F NMR (282 MHz, C6D6): δ −68.24 (br, CF3 PrF),
i
i
−68.68 (br, CF3 PrF), −70.11 (br, CF3 PrF), −204.65 (br, CFiPrF). 1H
NMR (300 MHz, C6D6, 50 °C): δ 1.45 (td, 3JHH = 7 Hz, 4JHH = 2 Hz,
6H, MeEt), 4.87 (br, 4H, CH2Et), 6.34 (t “multiplet”, JHH = 7 Hz,
3
3
2H, CHPy), 6.50 (d, JHH = 7 Hz, 2H, CHPy), 6.67 (t “multiplet”,
1
stated otherwise. H NMR spectra were referenced to residual proton
3JHH = 7 Hz, 2H, CHPy), 9.49 (br, 2H, CHPy). 19F NMR (282 MHz,
peaks associated with the deuterated solvents (C6D6: 7.16 ppm). 19F
NMR spectra were referenced to internal standard hexafluorobenzene
(C6F6, Oakwood, 99%), unless stated otherwise, set to −164.5 ppm.
13C{1H} NMR data were referenced to carbon peaks associated with
the solvent (C6D6, 128.39 ppm; THF, 67.57 ppm). 31P{1H} NMR
data were referenced to external H3PO4 (85% aqueous solution), set to
0.0 ppm. Electrospray ionization mass spectral data were collected
using an Applied Biosystem API2000 triple quadrupole mass
spectrometer. UV−vis spectra were recorded on a Cary 100
instrument, using sealable quartz cuvettes (1.0 cm path length). IR
data were obtained on a Nicolet Nexus 6700 FT-IR spectrometer. For
3a, the sample was prepared by allowing a benzene solution of 1 to
evaporate on a NaCl plate under a stream of nitrogen. Elemental
i
C6D6, 50 °C): δ −68.56 (br, CF3 PrF), −206.10 (br, CFiPrF). Anal.
Calcd for C17H18BrF7N2Ni: C, 39.12, H, 3.48, N, 5.37. Found: C,
38.37, H, 3.71, N, 5.16. See Figures S5 and S6 for H and 19F NMR
1
spectra. See Figures S7 and S8 for 1H and 19F NMR spectra at 50 °C.
In Situ Synthesis of [(PyEt)2Ni(Ph)(hfip)] (2b). The pink
complex [(PyEt)2NiBr(hfip)] (20 mg, 0.04 mmol) was placed in a 5
mL round-bottom flask and mixed with 1 mL of THF. A 1 mL
colorless solution of Ph2Zn in THF (9 mg, 0.04 mmol) was then
added to the solution, affording a yellow-brown solution after 10 min
i
that was used as is. 19F NMR (282 MHz, C6D6): δ −66.70 (br, CF3 PrF
i
(2b′)), −67.39 (“quint”, 3JFF = 4JFF = 9 Hz, CF3 PrF (2b′′), −68.00 (d,
3JFF = 10 Hz, CF3 PrF (2b′′′)), −68.01 (br, CFiPrF (2b′)), −69.14
i
3
4
i
(“quint”, JFF = JFF = 9 Hz, CF3 PrF (2b′′)), −197.33 (br, CFiPrF
(2b′)), −214.80 (sept, 3JFF = 9 Hz, CFiPrF (2b′′)), −215.26 (sept, 3JFF
= 10 Hz, CFiPrF (2b′′′)). See Figure S9 for 19F NMR spectra.
Synthesis of [(dcpe)Ni(Ph)(hfip)] (2c). To a 5 mL solution of
complex 2b in THF (100 mg, 0.19 mmol, vide supra) was added solid
dcpe (89 mg, 0.21 mmol). On stirring at 25 °C over 1 h, the solution
became progressively lighter yellow with concomitant formation of a
black precipitate. The light yellow solution was filtered through a
Celite pad (15 mL medium-pore fritted funnel), and the remaining
solvent was removed in vacuo to yield a light yellow powder. Roughly
5 mL of acetonitrile was added and the solid was collected (15 mL
́ ́
analyses were performed by Laboratoire d’analyze elementaire,
́ ́
Universite de Montreal (Montreal, Quebec, Canada). Note that the
NMR spectra (1H, 19F, 19F{1H}, 31P{1H} and 13C{1H}) for the title
compounds are displayed in the Supporting Information.
Synthesis of [(Htmp)Ag(hfip)] (1). AgF (500 mg, 3.94 mmol)
was placed in a 100 mL ampule and mixed with 15 mL of THF.
Colorless Htmp (612 mg, 4.34 mmol) was then added to the slurry.
The reaction vessel was attached via a three-way valve to an HFP
canister with a regulator and a Schlenk line. The solution was degassed
using a regular freeze/pump/thaw method. The HFP was added to the
degassed solution with the regulator set to 5 psi. The reaction mixture
G
DOI: 10.1021/acs.organomet.7b00837
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
medium-pore fritted funnel), washed with Et2O (4 °C, 3 × 3 mL), and
dried in vacuo to yield 105 mg of 2c (0.14 mmol, 75% based on
(PyEt)2NiBr2). UV−vis (1.5 mM in THF): λmax (ε) 373 (882), 307
((PPh3)CuH)6). IR: 3053(m,br), 1480(m), 1434(s,sh), 1292(w),
1
1231(w), 1146(w), 1116(w), 1094(w), 741(s,sh), 639(s,sh) cm−1. H
NMR (300 MHz, C6D6): δ 6.88 (m, 18H, Ar), 7.31 (m, 12H, Ar). 19
F
NMR (282 MHz, C6D6): δ −68.93 (br, CF3 PrF), −207.98 (br,
CFiPrF). 31P{1H} NMR (121 MHz, C6D6): δ −4.66 (s, PPh3). Anal.
Calcd for C39H30CuF7P2: C, 61.87, H, 3.99. Found: C, 63.47, H, 4.12.
1
i
nm (2348 M−1 cm−1)). H NMR (300 MHz, C6D6): δ 7.89 (m, 2H,
Ar), 7.05 (m, 2H, Ar), 6.91 (m, 1H, Ar), 2.5−0.5 (overlap, 48H, Cy
and CH2Et). 19F NMR (282 MHz, THF): δ −65.19 (dd, 4JFP = 5 Hz,
1
See Figures S15−S17 for H, 19F, and 31P{1H} NMR spectra.
i
4
4
3JFF = 13 Hz, CF3 PrF), −169.28 (dsept, JFP = 96 Hz, JFF = 13 Hz,
CFiPrF). 13C{1H} NMR (75 MHz, THF): δ 153.1 (dd, JPC = 76 Hz,
2
Synthesis of (PPh3)2(phen)Cu(hfip) (3b). The colorless complex
[(PPh3)2Cu(hfip)] (500 mg, 0.66 mmol) was placed in a 20 mL
scintillation vial and mixed with 10 mL of Et2O. Phen (130 mg, 0.73
mmol) was then added slowly while the solution was vigorously
stirred. The reaction mixture was stirred for 1 h as it changed from
clear to deep orange with a significant amount of orange precipitate.
Roughly 10 mL of hexanes was added, and the solid was collected (15
mL medium-pore fritted funnel). The solid was dissolved in 10 mL of
DME, the solution was filtered through a Celite-padded frit (15 mL
medium-pore fritted funnel), 50 mL of hexanes was added, and the
solid was collected, washed with hexanes (3 × 10 mL), and dried in
vacuo to yield 356 mg of 3b (0.53 mmol, 80% based on 3a). The
isolated material was stored at room temperature under nitrogen. A
second crop of product could be collected by crystallizing from the
remaining solution at −35 °C. UV−vis (1.0 mM in benzene): λmax (ε)
2JPC = 43 Hz, CαAr), 137.9 (CAr), 124.9 (CAr), 121.1 (CAr), 36.2
(“multiplet”, dcpe), 34.5 (“multiplet”, dcpe), 29.9−24 (overlap(THF),
dcpe), 20.0 (“multiplet”, dcpe). 31P{1H} NMR (121 MHz, THF): δ
57.81 (dd, 3JPF = 96 Hz, 2JPP = 31 Hz, P-trans-hfip), 47.75 (dsept, 2JPP
4
= 31 Hz, JPF = 6 Hz, P-cis-hfip). Compound 2c proved to be quite
hygroscopic and sensitive to air and moisture. Collection of elemental
analysis data returned a value closest to [(Cy2PCH2CH2P(O)Cy2)-
Ni(Ph)(hfip)·2H2O]. Anal. Calcd for C35H57F7NiO3P2: C, 53.93; H,
1
7.37. Found: C, 53.98; H, 7.28. See Figures S10−S13 for H, 19F,
13C{1H}, and 31P[1H] NMR spectra.
In Situ Synthesis of [(dcpe)NiC(O)Ph(hfip)] (2c′). A J. Young
NMR tube containing a 0.6 mL solution of complex 2c in C6D6 or
THF (20 mg, 0.028 mmol) was degassed, and CO (1 atm) was added.
The tube was heated for 2 h at 50 °C to produce a mixture [6:7:1] of
2c, 2c’ and 4a respectively. 19F NMR (282 MHz, C6D6): δ −66.24
1
395 nm (1276 M−1 cm−1). H NMR (300 MHz, C6D6): δ 8.88 (br,
i
(“quint”, 3JFF = 4JFF = 9 Hz, CF3 PrF), −67.22 (“quint”, 3JFF = 4JFF = 9
2H, phen), 7.49 (m, 6H, PPh3), 7.28 (m, 2H, phen), 6.99 (s, 2H,
phen), 6.90 (m, 9H, PPh3), 6.72 (m, 2H, phen). 19F NMR (282 MHz,
i
Hz, CF3 PrF), −167.619 (m, 3JFF = 4JFF = 9 Hz, 3JFP = 26 Hz, 3JFP = 120
3
i
3
C6D6): δ −67.39 (d, JFF = 10 Hz, CF3 PrF), −209.05 (sept, JFF = 10
Hz, CFiPrF). 31P{1H} NMR (121 MHz, C6D6): δ −4.95 (br, PPh3).
Anal. Calcd for C33H23CuF7N2P: C, 58.71, H, 3.43, N, 4.15. Found: C,
58.18, H, 3.51, N, 4.15. See Figures S18−S20 for 1H, 19F, and 31P{1H}
NMR spectra.
Hz, CFiPrF). 31P{1H} NMR (121 MHz, C6D6): δ 45.15 (m, 3JFP = 120
3
Hz), 39.48 (m, JFP = 26 Hz). N.B.: for the reaction to go to completion
(yield 90%) 3 atm of CO should be employed. See Figures S21−S24 for
19F and 31P{1H} NMR spectra of the reaction carried out at 1 atm
(30% yield).
Perfluoroisopropylation of Acid Chlorides: General Proce-
dure. The copper complex 3b (50 mg, 0.07 mmol) was loaded into an
NMR tube and mixed with DMF. The benzoyl chloride (A mg, 0.05
mmol) was then added to the solution. The reaction was left to sit at
room temperature for 24 h. The reaction mixture changed from deep
orange-red to light orange with a significant amount of orange
precipitate being formed. See Figures S25−S36 for 19F NMR spectra.
In Situ Synthesis of [(dppf)Ni(Ph)(hfip)] (2d). In a J. Young
NMR tube containing a 0.6 mL solution of complex 2b in THF (20
mg, 0.04 mmol) was placed solid dppf (21 mg, 0.04 mmol). The
solution became deep orange and was used as is. 19F NMR (282 MHz,
i
C64D6): δ −65.16 (d, 3JFF = 9 Hz, CF3 PrF (2d)), −66.30 (“quint”, 3JFF
i
3
4
= JFF = 9 Hz, CF3 PrF (2d′)), −67.96 (“quint”, JFF = JFF = 9 Hz,
i
3
4
3
CF3 PrF (2d′)), −166.99 (br m, JFF = JFF = 9 Hz, JFP = 150 Hz,
CFiPrF (2d)), −200.42 (sext, 3JFP = 3JFF = 4JFF = 9 Hz, CFiPrF (2d′)).
See Figure S14 for 19F NMR spectrum.
PhC(O)(hfip) (4a). 19F NMR (282 MHz, DMF): δ −73.95 (d, 3JFF
=
i
7 Hz, CF3 PrF), −179.17 (m, 3JFF = 7 Hz, CFiPrF). GC-MS (retention
time 3.91 min): expected, 274.1; found, 274.1.
Synthesis of [(PPh3)2Cu(hfip)] (3a). Method A. The colorless
complex [(PPh3)3CuF] (500 mg, 0.56 mmol) was placed in a 100 mL
ampule and mixed with 30 mL of Et2O. The reaction vessel was
attached via a three-way valve to an HFP canister with a regulator and
a Schlenk line. The solution was degassed using a regular freeze/
pump/thaw method. The HFP was added to the degassed solution
with the regulator set to 5 psi. The reaction mixture was stirred at 25
°C for ∼24 h. A colorless precipitate remained over the course of the
reaction. The solvent was removed in vacuo, 10 mL of DME was
added, and this solution was filtered through a Celite pad (15 mL
medium-pore fritted funnel) to remove unreacted Cu−F. The volatiles
were removed in vacuo, and roughly 10 mL of hexanes was added. The
solid was collected (15 mL medium-pore fritted funnel), triturated
with hexanes (3 × 10 mL), and dried in vacuo to yield 391 mg of 3a
(0.52 mmol, 90% based on (PPh3)3CuF). The isolated material was
stored at room temperature under nitrogen.
Method B. The red complex [(PPh3)CuH]6 (5.23 g, 16 mmol based
on monomeric unit) and PPh3 (5.03 g, 19.2 mmol) were placed in a 1
L Schlenk round-bottom flask and mixed with 100 mL of benzene.
The reaction vessel was attached via a three-way valve to an HFP
canister with a regulator and a Schlenk line. The solution was degassed
using a regular freeze/pump/thaw method. The HFP was added to the
degassed solution with the regulator set to 5 psi and the reaction
mixture stirred at 25 °C for ∼2 h. The solution became light yellow.
The solvent was removed in vacuo, leaving a buff powder. The powder
was dissolved in DME (100 mL) and stirred vigorously. The solution
was then filtered (15 mL medium pore fritted funnel) and the solvent
removed in vacuo. The solid was collected (30 mL medium-pore
fritted funnel), triturated with cold Et2O (−35 °C, 3 × 20 mL), and
dried in vacuo to yield 9.81 g of 3a (12.96 mmol, 81% based on
3,4,5-(OMe)3-PhC(O)(hfip) (4b). 19F NMR (282 MHz, DMF): δ
3
i
3
−73.93 (d, JFF = 7 Hz, CF3 PrF), −177.79 (m, JFF = 7 Hz, CFiPrF).
GC-MS (retention time 7.11 min): expected, 364.1 (100%); found,
364.1 (100%).
p-Me-PhC(O)(hfip) (4c). 19F NMR (282 MHz, DMF): δ −74.50 (d,
i
3
3JFF = 7 Hz, CF3 PrF), −179.19 (m, JFF = 7 Hz, CFiPrF). GC-MS
(retention time 4.63 min): expected, 288.1; found, 288.1.
o-Me-PhC(O)(hfip) (4d). 19F NMR (282 MHz, DMF): δ −74.19 (d,
i
3
3JFF = 7 Hz, CF3 PrF), −177.46 (m, JFF = 7 Hz, CFiPrF). GC-MS:
(rentention time: 4.34 min): expected, 288.1; found, 288.1.
m-Br-Ph(CO)(hfip) (4e). 19F NMR (282 MHz, DMF): δ −74.50 (d,
i
3
3JFF = 7 Hz, CF3 PrF), −179.85 (m, JFF = 7 Hz, CFiPrF). GC-MS
(retention time 5.16 min): expected, 351.9 (100%), 353.9 (97.3%);
found, 351.9 (100%), 353.9 (93%).
p-F-PhC(O)(hfip) (4f). 19F NMR (282 MHz, DMF): δ −73.99 (d,
i
3
3JFF = 7 Hz, CF3 PrF), −101.26 (m, F−Ar), −178.43 (m, JFF = 7 Hz,
CFiPrF). GC-MS (retention time 3.75 min): expected, 292.0 (100%).
Found: 291.9 (100%).
p-Br-Ph(CO)(hfip) (4g). 19F NMR (282 MHz, DMF): δ −73.97 (d,
i
3
3JFF = 8 Hz, CF3 PrF), −178.90 (d“multiplet”, JFF = 8 Hz, CFiPrF).
GC-MS (retention time 5.22 min): expected, 351.9 (100%), 353.9
(97.3%); found, 352.1 (100%), 354.0 (90%).
p-CN-PhC(O)(hfip) (4i). 19F NMR (282 MHz, DMF): δ −73.9 (d,
3JFF = 7 Hz, CF3 Pr), −179.45 (d“multiplet”, 3JFF = 7 Hz, CFiPrF). GC-
i
MS (retention time 5.30 min). expected, 299.0 (100%); found, 299.1
(100%).
p-NO2-PhC(O)(hfip) (4j). 19F NMR (282 MHz, DMF): δ −73.87 (d,
i
3JFF = 7 Hz, CF3 PrF), −179.30 (m, 3JFF = 7 Hz, CFiPrF). GC-MS: N/
A.
H
DOI: 10.1021/acs.organomet.7b00837
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
o-NO2-PhC(O)(hfip) (4k). 19F NMR (282 MHz, DMF): δ −73.90
(d, 3JFF = 7 Hz, CF3iPrF), −179.45 (m, 3JFF = 7 Hz, CFiPrF). GC-MS:
N/A.
charge via www.ccdc.cam.ac.uk/data_request/cif, or by email-
ing data_request@ccdc.cam.ac.uk, or by contacting The
Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
2-Naph(CO)iPrF (4l). 19F NMR (282 MHz, DMF): δ −74.21 (d,
i
3
3JFF = 7 Hz, CF3 PrF), −176.83 (m, JFF = 7 Hz, CFiPrF). GC-MS
(retention time 6.70 min): expected, 324.0 (100%); found, 324.1
(100%).
AUTHOR INFORMATION
Corresponding Author
*E-mail for R.T.B.: rbaker@uottawa.ca.
■
2-Tp(CO)iPrF (4n). 19F NMR (282 MHz, DMF): δ −74.32 (d, JFF
3
i
3
= 7 Hz, CF3 PrF), −179.83 (m, JFF = 7 Hz, CFiPrF). GC-MS
(retention time 4.20 min): expected, 280.1 (100%); found, 280.0
(100%).
ORCID
David A. Dixon: 0000-0002-9492-0056
R. Tom Baker: 0000-0002-1133-7149
Notes
Synthesis of p-F-PhCH2(hfip) (5a). 19F NMR (282 MHz, DMF): δ
3
i
−75.86 (d, JFF = 7 Hz, CF3 PrF), −115.91 (m, F−Ar), −182.76 (t
sept, 3JFH = 24 Hz, 3JFF = 7 Hz, CFiPrF). GC-MS (retention time 3.82
min) expected, 278.0 (100%); found, 278.1 (100%).36 See Figure S36
for 19F NMR spectra.
The authors declare no competing financial interest.
Synthesis of p-F-PhCH(OH)(hfip) (5b). 19F NMR (376.5 MHz,
ACKNOWLEDGMENTS
i
C6D6): −70.40 (“quint”, 3JFF = 4JFF = 9 Hz, CF3 PrF), −73.23 (“quint”,
■
3JFF = JFF = 9 Hz, CF3 PrF), −111.51 (m, F−Ar), −179.55 (d sept,
3JFH = 12 Hz, 3JFF = 9 Hz, CFiPrF). GC-MS (retention time 5.01 min)
expected, 294.0 (100%); found, 294.0 (100%).37 See Figures S37 and
S38 for 19F NMR spectra.
4
i
We thank the NSERC and the Canada Research Chairs
program for generous financial support and the University of
Ottawa, Canada Foundation for Innovation and Ontario
Ministry of Economic Development and Innovation for
essential infrastructure. NOA gratefully acknowledges support
from the province of Ontario, NSERC and the University of
Ottawa (OGS and CGS-M/D). The computational work at UA
was supported by the Chemical Sciences, Geosciences and
Biosciences Division, Office of Basic Energy Sciences, U.S.
Department of Energy (DOE) under the DOE BES Catalysis
Center Program by a subcontract from Pacific Northwest
National Laboratory (KC0301050-47319). DAD also thanks
the Robert Ramsay Chair Fund of The University of Alabama
for support.
Computational Methods. The geometries were optimized at the
density functional theory (DFT)38 level with the hybrid B3LYP39,40
with the DFT-optimized DZVP2 basis set41 for H, N, C, F, and P
atoms and aug-cc-pVDZ-PP42,43 basis sets for M = Ag, Ni, Cu using
the Gaussian09 program system.44 Vibrational frequencies were
calculated to show that the structures were minima. The B3LYP/
DZVP2/aug-cc-pVDZ-PP(M) geometries were used to predict the
NMR chemical shifts for F (19F NMR) and P (31P NMR) in C6H6
using the ADF program system45,46 with the BLYP47 functional and
the TZ2P basis set in ADF.48 Scalar relativistic effects were included at
the two-component zero-order regular approximation (ZORA) level
for the NMR calculations.49−51 The 19F NMR and 31P NMR chemical
shifts are reported relative to their specific standards CFCl3 and
H3PO4 calculated at the same level.
Using the gas-phase geometries, the solvation free energies in DMF
at 298 K were calculated using the self-consistent reaction field
(SCRF) approach52 with the COSMO parameters53,54 as implemented
in Gaussian 0944 at the same B3LYP/DZVP2 level of theory using the
COSMO radii. The Gibbs free energy in DMF solution, ΔGDMF, was
calculated from eq 1.
REFERENCES
■
(1) Banks, R. E.; Smart, B. E.; Tatlow, J. C. Organofluorine Chemistry:
Principles and Commercial Applications; Plenum: New York, 1994.
(2) Chambers, R. D. Fluorine Chemistry at the Millennium; Elsevier:
Amsterdam, 2000.
(3) Gouverneur, V.; Muller, K. Fluorine in Pharmaceutical and
̈
Medicinal Chemistry; Imperial College Press: London, 2012.
(4) Purser, S.; Moore, P. R.; Swallow, S.; Gouverneur, V. Chem. Soc.
Rev. 2008, 37, 320−330.
ΔGDMF = ΔGgas + ΔGSOLV
(1)
́ ́
(5) Wang, J.; Sanchez-Rosello, M.; Acena, J. L.; del Pozo, C.;
̃
where ΔGgas is the gas phase free energy and ΔGsolv is the solvation
free energy in DMF. A dielectric constant of 37.22 corresponding to
that of bulk DMF was used in the COSMO calculations.
The Natural Population Analysis based on the Natural Bond
Orbitals (NBOs)55,56 using NBO657,58 with wave functions are
calculated at the B3LYP/DZVP2/aug-cc-pVDZ-PP(M) density func-
tional theory level using Gaussian09.
The calculations were performed on a Xeon-based Dell Linux
cluster at the University of Alabama, and a local AMD Opteron-based
and Intel Xeon-based Linux cluster from Penguin Computing.
Sorochinsky, A. E.; Fustero, S.; Soloshonok, V. A.; Liu, H. Chem. Rev.
2014, 114, 2432−2506.
(6) (a) Charpentier, J.; Fruh, N.; Togni, A. Chem. Rev. 2015, 115,
̈
650−682. (b) Yang, X.; Wu, T.; Phipps, J.; Toste, F. D. Chem. Rev.
2015, 115, 826−870. (c) Alonso, C.; Martínez de Marigorta, E.;
Rubiales, G.; Palacios, F. Chem. Rev. 2015, 115, 1847−1935. (d) Gao,
P.; Song, S.-R.; Liu, X.-Y.; Liang, Y.-M. Chem. - Eur. J. 2015, 21, 7648−
7661. (e) Kyasa, S. Synlett 2015, 26, 1911−1912. (f) Wang, S.-M.;
Han, J.-B.; Zhang, C.-P.; Qin, H.-L.; Xia, J.-C. Tetrahedron 2015, 71,
7949−7976.
(7) (a) Hu, J.; Zhang, W.; Wang, F. Chem. Commun. 2009, 7465−
7478. (b) Lu, Y.; Liu, C.; Chen, Y.-C. Curr. Org. Chem. 2015, 19,
1638−1650. (c) Chen, B.; Vicic, D.. Transition-Metal-Catalyzed
Difluoromethylation, Difluoromethylenation, and Polydifluoromethy-
lenation Reactions. In Organometallic Fluorine Chemistry; Braun, T.,
Hughes, R. P., Eds.; Springer US: New York, 2014; Topics in
Organometallic Chemistry 52, pp 113−141. (d) Serizawa, H.; Ishii, K.;
Aikawa, K.; Mikami, K. Org. Lett. 2016, 18, 3686−3689.
(8) (a) Huang, Y.; Ajitha, M. J.; Huang, K.-W.; Zhang, Z.; Weng, Z.
Dalton Trans. 2016, 45, 8468−8474. (b) Sugiishi, T.; Amii, H.; Aikawa,
K.; Mikami, K. Beilstein J. Org. Chem. 2015, 11, 2661−2670. (c) Li, L.;
Ni, C.; Xie, Q.; Hu, M.; Wang, F.; Hu, J. Angew. Chem., Int. Ed. 2017,
56, 9971−9975.
(9) (a) Landelle, G.; Panossian, A.; Leroux, F. R. Curr. Top. Med.
Chem. 2014, 14, 941−951. (b) Lee, K.; Lee, J.; Ngai, M.-Y. Synlett
ASSOCIATED CONTENT
* Supporting Information
This material is available free of charge via the Internet at
http://pubs.acs.org.” The Supporting Information is available
free of charge on the ACS Publications website at DOI:
10.1021/acs.organomet.7b00837.
■
S
Additional crystallographic information, DFT studies,
and 1H, 19F, 13C{1H} and 31P{1H} NMR spectra. (PDF)
optimized Cartesian coordinates in Å (PDF)
Accession Codes
CCDC 1586727−1586731 contain the supplementary crystal-
lographic data for this paper. These data can be obtained free of
I
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Organometallics
Article
2016, 27, 313−319. (c) Besset, T.; Jubault, P.; Pannecoucke, X.;
Poisson, T. Org. Chem. Front. 2016, 3, 1004−1010.
D. J.; Daniels, A. L.; Korobkov, I.; Baker, R. T. Organometallics 2015,
34, 4598−4604.
(25) (a) Gulliver, D. J.; Levason, W.; Webster, M. Inorg. Chim. Acta
1981, 52, 153−159. (b) Chaudhuri, M. K.; Dhar, S. S.; Viayashree, N.
Transition Met. Chem. 2000, 25, 559−561.
(10) (a) Landelle, G.; Panossian, A.; Pazenok, S.; Vors, J.-P.; Leroux,
F. R. Beilstein J. Org. Chem. 2013, 9, 2476−2536. (b) Barata-Vallejo, S.;
Bonesi, S.; Postigo, A. Org. Biomol. Chem. 2016, 14, 7150−7182.
(11) (a) Tohnishi, M.; Nakao, H.; Kohno, E.; Nishida, T.; Furuya, T.;
Shimizu, T.; Seo, A.; Sakata, K.; Fujioka, S.; Kanno, H. EP 919542,
1999. (b) Tohnishi, M.; Nakao, H.; Kohno, E.; Nishida, T.; Furuya, T.;
Shimizu, T.; Seo, A.; Sakata, K.; Fujioka, S.; Kanno, H. EP 1006107,
2000. (c) Kimura, M.; Morimoto, M.; Uehara, M.; Watanabe, M.;
Yoshida, M. EP 1097932A1, 2001. (d) Zhang, J.; Tang, X.; Ishaaya, I.;
Cao, S.; Wu, J.; Yu, J.; Li, H.; Quain, X. J. Agric. Food Chem. 2010, 58,
2736−2740. Zhou, S.; Meng, X.; Jin, R.; Ma, Y.; Xie, Y.; Zhao, Y.;
Song, H.; Xiong, L.; Li, Z. Mol. Diversity 2017, 21, 915.
(12) Prakash, G. K. S.; Hu, J.; Olah, G. A. J. Org. Chem. 2003, 68,
4457−4463.
(26) Larsson, J. M.; Pathipati, S. R.; Szabo,
78, 7330−7336.
(27) Tomashenko, O. A.; Escudero-Adan
́
K. J. J. Org. Chem. 2013,
́
, E. C.; Belmonte, M. M.;
Grushin, V. V. Angew. Chem., Int. Ed. 2011, 50, 7655−7659.
(28) Panferova, L. I.; Miloserdov, F. M.; Lishchynskyi, A.; Belmonte,
M. M.; Benet-Buchholz, J.; Grushin, V. V. Angew. Chem., Int. Ed. 2015,
54, 5218−5222.
(29) Kikushima, K.; Sakaguchi, H.; Saijo, H.; Ohashi, M.; Ogoshi, S.
Chem. Lett. 2015, 44, 1019−1021. More recently, oxycupration:
Ohashi, M.; Adachi, T.; Ishida, N.; Kikushima, K.; Ogoshi, S. Angew.
Chem., Int. Ed. 2017, 56, 11911−11915.
(30) Lv, H.; Cai, Y.-B.; Zhang, J.-L. Angew. Chem., Int. Ed. 2013, 52,
3203−3207.
(31) It should be noted that the scope of both referenced reactions
was quite limited.
(32) The vacuum transfer procedure was done for 4f and 4n.
(33) Note that 3b undergoes homolysis at room temperature only in
the presence of an electrophile.
(34) (a) Zhu, F.; Yang, G.; Zhou, S.; Wu, X.-F. RSC Adv. 2016, 6,
57070−57074. (b) Braun, T.; Parsons, S.; Perutz, R. N.; Voith, M.
Organometallics 1999, 18, 1710−1716.
(35) Curtiss, L. A.; Redfern, P. C.; Raghavachari, K.; Rassolov, V.;
Pople, J. A. J. Chem. Phys. 1999, 110, 4703−4709.
(36) Characterization data match those of some reported benzyl-hfip
and analogous alkyl-hfip compounds: (a) Dneprovskii, A. S.;
Kasatochkin, A. N.; Kondakov, D. Y. Russ. J. Org. Chem. 1989, 25,
1984−1991. (b) Ignatowska, J.; Wojciech, D. J. Fluorine Chem. 2007,
128, 997−1006.
(37) Characterization data match those of some reported
arylcarbinol-hfip compounds: (a) O’ Reilly, N. J.; Maruta, M.;
Ishikawa, N. Chem. Lett. 1984, 13, 517−520. (b) Kitazume, T.;
Ishikawa, N. J. Am. Chem. Soc. 1985, 107, 5186−5191. (c) Kitazume,
T.; Ishikawa, N. Chem. Lett. 1981, 10, 1337−1338.
(38) Parr, R. G.; Yang, W. Density-Functional Theory of Atoms and
Molecules; Oxford University Press: New York, 1989.
(39) Becke, A. D. J. Chem. Phys. 1993, 98, 5648−5652.
(40) Lee, C.; Yang, W.; Parr, R. G. Phys. Rev. B: Condens. Matter
Mater. Phys. 1988, 37, 785−789.
(41) Godbout, N.; Salahub, D. R.; Andzelm, J.; Wimmer, E. Can. J.
Chem. 1992, 70, 560−571.
(42) Peterson, K. A.; Puzzarini, C. Theor. Chem. Acc. 2005, 114, 283−
296.
(43) Peterson, K. A.; Figgen, D.; Dolg, M.; Stoll, H. J. Chem. Phys.
2007, 126, 124101.
(44) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.;
Robb, M. A.; Cheeseman, J. R.; Scalmani, G.; Barone, V.; Mennucci,
B.; Petersson, G. A., et al. Gaussian 09, Revision A.2; Gaussian, Inc.,
Wallingford, CT, 2009.
(45) te Velde, G.; Bickelhaupt, F. M.; van Gisbergen, S. J. A.; Fonseca
Guerra, C.; Baerends, E. J.; Snijders, J. G.; Ziegler, T. J. Comput. Chem.
2001, 22, 931−967.
(46) ADF 2017, ADF Users Guide; SCM, Theoretical Chemistry,
Vrije Universiteit: Amsterdam; http://www.scm.com, Accessed 6-15-
2017.
(13) Lishchynskyi, A.; Grushin, V. V. J. Am. Chem. Soc. 2013, 135,
12584−12587.
(14) Xu, L.; Vicic, D. A. J. Am. Chem. Soc. 2016, 138, 2536−2539.
(15) Morimoto, H.; Tsubogo, T.; Litvinas, N. D.; Hartwig, J. F.
Angew. Chem., Int. Ed. 2011, 50, 3793−3798.
(16) (a) Ishikawa, N.; Shin-ya, S. Bull. Chem. Soc. Jpn. 1975, 48,
1339−1340. (b) Takechi, N.; Aït-Mohand, S.; Med
́
ebielle, M.; Dolbier,
W. R., Jr. Tetrahedron Lett. 2002, 43, 4317−4319.
(17) (a) Naumann, D.; Finke, M.; Lange, H.; Dukat, W.; Tyrra, W. J.
Fluorine Chem. 1992, 56, 215−237. (b) Chambers, R. D.; Musgrave,
W. K. R.; Savory, J. J. Chem. Soc. 1962, 0, 1993−1991. (c) Nair, H. K.;
Burton, D. J. J. Fluorine Chem. 1992, 56, 341−351. (d) Ishikawa, N.;
Ochiai, M. Nippon Kagaku Kaishi 1973, 1973, 2351−2356.
(e) McLoughlin, V. C. R.; Thrower, J. Tetrahedron 1969, 25, 5921−
5940. (f) Burch, R. R.; Calabrese, J. C. J. Am. Chem. Soc. 1986, 108,
5359−5360. (g) Naumann, D.; Wessel, W.; Hahn, J.; Tyrra, W. J.
Organomet. Chem. 1997, 547, 79−88. (h) Bubot, G.; Mansuy, D.;
Lecolier, S.; Normant, J. F. J. Organomet. Chem. 1972, 42, C105−
C106. (i) Sekiya, A.; Ishikawa, N. Chem. Lett. 1977, 6, 81−84.
(18) (a) Toscano, P. J.; Brand, H.; Geremia, S.; Randaccio, L.;
Zangrando, E. Organometallics 1991, 10, 713−720. (b) Jiang, D.-F.;
Liu, C.; Guo, Y.; Xiao, J.-C.; Chen, Q.-Y. Eur. J. Org. Chem. 2014,
2014, 6303−6309.
(19) (a) Miller, W. T.; Burnard, R. J. J. Am. Chem. Soc. 1968, 90,
7367−7368. (b) Dyatkin, B. L.; Martynov, B. I.; Martynova, L. G.;
Kizim, N. G.; Sterlin, S. R.; Stumbrevichute, Z. A.; Fedorov, L. A. J.
Organomet. Chem. 1973, 57, 423−433.
(20) (a) Simon, C. M.; Kaminsky, W. Polym. Degrad. Stab. 1998, 62,
1−7. (b) Van der Walt, I. J.; Grunenburg, A. T.; Nel, J. T.; Maluleke,
G. G.; Bruinsma, S. L. J. Appl. Polym. Sci. 2008, 109, 264−271.
(21) (a) Li, Y.; Wang, X.; Guo, Y.; Zhu, Z.; Wu, Y.; Gong, Y. Chem.
Commun. 2016, 52, 796−799. (b) Wang, X.; Li, Y.; Guo, Y.; Zhu, Z.;
Wu, Y.; Cao, W. Org. Chem. Front. 2016, 3, 304−308. (c) Liu, X.-H.;
Leng, J.; Jia, S.-J.; Hao, J.-H.; Zhang, F.; Qin, H.-L.; Zhang, C. P. J.
Fluorine Chem. 2016, 189, 59−67.
(22) Zeng, Y.; Zhang, L.; Zhao, Y.; Ni, C.; Zhao, J.; Hu, J. J. Am.
Chem. Soc. 2013, 135, 2955−2958.
(23) Example of successful transmetalation with silver perfluoroalkyl
to nickel: Zhang, C.-P.; Wang, H.; Klein, A.; Biewer, C.; Stirnat, K.;
Yamaguchi, Y.; Xu, L.; Gomez-Benitez, V.; Vicic, D. A. J. Am. Chem.
Soc. 2013, 135, 8141−8144.
(24) Examples of M−RF compounds with elongated Cα−F bonds:
(a) Hughes, R. P. J. Fluorine Chem. 2010, 131, 1059−1070.
(b) Goodman, J.; Grushin, V. V.; Larichev, R. B.; Macgregor, S. A.;
Marshall, W. J.; Roe, D. C. J. Am. Chem. Soc. 2009, 131, 4236−4238.
(c) Garratt, S. A.; Hughes, R. P.; Kovacik, I.; Ward, A. J.; Willemsen,
S.; Zhang, D. J. Am. Chem. Soc. 2005, 127, 15585−15594. (d) Torrens,
H. Coord. Chem. Rev. 2005, 249, 1957−1985. (e) Huang, D.; Koren, P.
R.; Folting, K.; Davidson, E. R.; Caulton, K. G. J. Am. Chem. Soc. 2000,
122, 8916−8931. (f) Richmond, T. G.; Shriver, D. F. Organometallics
1984, 3, 314−319. (g) Richmond, T. G.; Shriver, D. F. Organometallics
1983, 2, 1061−1062. (h) Andrella, N. O.; Sicard, A. J.; Gorelsky, S. I.;
Korobkov, I.; Baker, R. T. Chem. Sci. 2015, 6, 6392−6397. (i) Harrison,
(47) Becke, A. D. Phys. Rev. A: At., Mol., Opt. Phys. 1988, 38, 3098−
3100.
(48) ADF 2008.01, ADF Users Guide; SCM, Theoretical Chemistry,
Vrije Universiteit: Amsterdam, 2008; http://www.scm.com.
(49) Wolff, S. K.; Ziegler, T.; van Lenthe, E.; Baerends, E. J. J. Chem.
Phys. 1999, 110, 7689−7698.
(50) van Lenthe, E.; Baerends, E. J.; Snijders, J. G. J. Chem. Phys.
1993, 99, 4597−4610.
J
DOI: 10.1021/acs.organomet.7b00837
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
(51) Autschbach, J.; Ziegler, T. In Calculation of NMR and EPR
Parameters: Theory and Application, Kaupp, M., Buhl, M., Malkin, V.
G., Eds.; Wiley-VCH: Weinheim, Germany, 2004; pp 249−264.
(52) Tomasi, J.; Mennucci, B.; Cammi, R. Chem. Rev. 2005, 105,
2999−3093.
(53) Klamt, A. Quantum Chemistry to Fluid Phase Thermodynamics
and Drug Design; Elsevier: Amsterdam, 2005.
(54) Klamt, A.; Schuurmann, G. J. Chem. Soc., Perkin Trans. 2 1993, 2,
̈
̈
799−805.
(55) Reed, A. E.; Curtiss, L. A.; Weinhold, F. Chem. Rev. 1988, 88,
899−926.
(56) Weinhold, F.; Landis, C. R. Valency and Bonding: A Natural
Bond Orbital Donor-Acceptor Perspective; University Press: Cambridge,
U.K., 2005.
(57) Glendening, E. D.; Badenhoop, J. K.; Reed, A. E.; Carpenter, J.
E.; Bohmann, J. A.; Morales, C. M.; Landis, C. R.; Weinhold, F.
Natural Bond Order 6.0; Theoretical Chemistry Institute, University of
Wisconsin, Madison, WI, 2013; http://nbo6.chem.wisc.edu/, accessed
12−01-2013.
(58) Glendening, E. D.; Landis, C. R.; Weinhold, F. J. Comput. Chem.
2013, 34, 1429−1437.
(59) Prepared by a modification of procedure for (2-methylpyr-
idine)2NiBr2: Vallarino, L. M.; Hill, W. E.; Quagliano, J. V. Inorg.
Chem. 1965, 4, 1598−1604.
K
DOI: 10.1021/acs.organomet.7b00837
Organometallics XXXX, XXX, XXX−XXX