Ortho derivatization of phenols through C-H nickelation: Synthesis, characterization, and reactivities of ortho-nickelated phosphinite complexes

Article abstract of DOI:10.1021/om500938u

Reported here are the synthesis and characterization of ortho-nickelated complexes derived from phosphinite ligands and investigated as model compounds in the development of C-H functionalization strategies for arenol substrates. Reaction of i-Pr₂POPh with 0.6 equiv of [(i-PrCN)NiBr₂]_n and 0.8 equiv of NEt₃ in toluene (100 °C, 36 h) gave the yellow, monomeric cyclometalated complex trans-{κ²P,C-C₆H₄OP(i-Pr)₂}Ni(i-Pr₂POPh)Br (3a) in 93% yield. The closely related yellow-orange dimeric species [{κ²P,C-C₆H₄OP(i-Pr)₂}Ni(μ-Br)]₂ (4a) was obtained in 70% yield when i-Pr₂POPh was treated with 2 equiv each of the Ni precursor and NEt₃. These complexes have been characterized fully and shown to interconvert in the presence of excess ligand (4a → 3a) or excess Ni precursor (3a → 4a). Treatment of 3a or 4a with benzyl bromide at 90°C over extended periods led to benzylation of the Ni-aryl moiety in these complexes. Examination of the cyclometalation pathway for i-Pr₂POPh has shown that the first species formed from its ambient-temperature reaction with [(i-PrCN)NiBr₂]_n is trans-(i-Pr₂POPh)₂NiBr₂ (2a). NMR studies showed that 2a undergoes a rapid ligand exchange at room temperature, which can be slowed down at -68°C; this fluxional process shifts in the presence of NEt₃, implying the partial formation of an amine adduct. Heating toluene mixtures of 2a and NEt₃ at 90°C for 38 h led to the formation of 3a via C-H nickelation. That phosphinite dissociation from 2a precedes the C-H nickelation step is implied by the observation that the formation of 3a is hindered in the presence of excess i-Pr₂POPh. The impact of phenol ring substituents on the C-H nickelation rate was probed by preparing substituted derivatives of 2a, trans-(4-R-C₆H₄OP(i-Pr₂)}₂NiBr₂ (R = OMe (2b), Me (2c), COOMe (2d)), and measuring their relative rates of C-H nickelation. These studies showed that the formation of cyclonickelated products is favored in the order COOMe < Me < OMe, which is consistent with an electrophilic nickelation mechanism. Studying the C-H nickelation of 3-F-C₆H₄OP(i-Pr₂) allowed us to establish that metalation is favored at the para position with respect to F (85:15).

Full text of DOI:10.1021/om500938u

Article
pubs.acs.org/Organometallics
Ortho Derivatization of Phenols through C−H Nickelation: Synthesis,
Characterization, and Reactivities of Ortho-Nickelated Phosphinite
Complexes
Boris Vabre, Felix Deschamps, and Davit Zargarian*
́
́ ́ ́ ́ ́
Departement de chimie, Universite de Montreal, Montreal, Quebec, Canada H3C 3J7
S
* Supporting Information
ABSTRACT: Reported here are the synthesis and character-
ization of ortho-nickelated complexes derived from phosphinite
ligands and investigated as model compounds in the develop-
ment of C−H functionalization strategies for arenol substrates.
Reaction of i-Pr2POPh with 0.6 equiv of [(i-PrCN)NiBr2]n and
0.8 equiv of NEt3 in toluene (100 °C, 36 h) gave the yellow,
monomeric cyclometalated complex trans-{κ2P,C-C6H4OP(i-
Pr)2}Ni(i-Pr2POPh)Br (3a) in 93% yield. The closely related
yellow-orange dimeric species [{κ2P,C-C6H4OP(i-Pr)2}Ni(μ-
Br)]2 (4a) was obtained in 70% yield when i-Pr2POPh was
treated with 2 equiv each of the Ni precursor and NEt3. These
complexes have been characterized fully and shown to
interconvert in the presence of excess ligand (4a → 3a) or excess Ni precursor (3a → 4a). Treatment of 3a or 4a with
benzyl bromide at 90 °C over extended periods led to benzylation of the Ni−aryl moiety in these complexes. Examination of the
cyclometalation pathway for i-Pr2POPh has shown that the first species formed from its ambient-temperature reaction with [(i-
PrCN)NiBr2]n is trans-(i-Pr2POPh)2NiBr2 (2a). NMR studies showed that 2a undergoes a rapid ligand exchange at room
temperature, which can be slowed down at −68 °C; this fluxional process shifts in the presence of NEt3, implying the partial
formation of an amine adduct. Heating toluene mixtures of 2a and NEt3 at 90 °C for 38 h led to the formation of 3a via C−H
nickelation. That phosphinite dissociation from 2a precedes the C−H nickelation step is implied by the observation that the
formation of 3a is hindered in the presence of excess i-Pr2POPh. The impact of phenol ring substituents on the C−H nickelation
rate was probed by preparing substituted derivatives of 2a, trans-(4-R-C6H4OP(i-Pr2)}2NiBr2 (R = OMe (2b), Me (2c), COOMe
(2d)), and measuring their relative rates of C−H nickelation. These studies showed that the formation of cyclonickelated
products is favored in the order COOMe < Me < OMe, which is consistent with an electrophilic nickelation mechanism.
Studying the C−H nickelation of 3-F-C6H4OP(i-Pr2) allowed us to establish that metalation is favored at the para position with
respect to F (85:15).
Scheme 1. Idealized Scheme for Chelation-Assisted, Direct
Functionalization of C−H Bonds
INTRODUCTION
■
Synthetic strategies based on C−H functionalization have
grown in prominence and constitute a central part of the
current global drive to develop sustainable chemical processes.1
The most facile and common strategy in the area of metal-
catalyzed C−H metalation relies on the presence in substrates
of nucleophilic moieties that can bind the metal atom to
facilitate its interaction with the C−H moiety to be activated.
This type of chelation-assisted approach based on “functional
directing groups” is commonly assumed to generate metalla-
cycles as key intermediates that react subsequently with
cosubstrates to give the products of functionalization (Scheme
1).
Whereas most C−H functionalization methodologies are
based on one-pot approaches that bypass isolation or even
detection of reaction intermediates, there are potentially
significant benefits in intercepting the initial cyclometalated
species and investigating the main factors influencing their
formation, stability, and reactivities. Any knowledge gained
from such studies should improve our understanding of the
important steps involved in catalytic C−H functionalization
processes and help develop more efficient methodologies.
Received: September 11, 2014
Published: November 4, 2014
© 2014 American Chemical Society
6623
dx.doi.org/10.1021/om500938u | Organometallics 2014, 33, 6623−6632

Organometallics
Article
A survey of the C−H functionalization literature reveals that
most of the early successes in this area hinged on the use of the
noble metals Ru,2 Rh and Ir,3 and Pd,4 but a recent drive
toward more sustainable C−H functionalization strategies has
led to greater use of the more abundant 3d counterparts of the
above-noted noble metals, namely Fe,5 Co,6 and Ni.7 The use
of Ni precursors in this context also has a historic significance,
since Ni was one of the earliest metals to show an aptitude in
C−H metalation.8 These considerations and our group’s
longstanding interest in organonickel chemistry9 have inspired
us to initiate projects aimed at developing C−H functionaliza-
tion methodologies based on Ni precursors.
of the target cyclometalated complexes, as follows. Refluxing a
toluene mixture of 1a, 0.6 equiv of our Ni precursor [(i-
PrCN)NiBr2]n,19 and 0.8 equiv of NEt3 gave a yellow solid
identified as 3a in 93% yield, whereas using 2 equiv each of the
Ni precursor and base gave the closely related yellow-orange
dimeric species 4a in 70% yield (Scheme 2). Complex 4a reacts
a
Scheme 2. Synthesis of Cyclometalated Complexes of Ni
In light of the aforementioned importance of metallacycles,
we have set out to prepare nickelacyclic complexes via C−H
nickelation and study their ease of formation, structures, and
reactivities as part of a long-term strategy aimed at developing
Ni-based C−H functionalization methodologies. An initial
search of the literature revealed that very few metallacyclic
complexes of Ni have been reported previously, especially in
comparison to the much better known analogues based on Pd
and Pt. Representative examples of reported nickelacycles
include complexes based on aromatic Schiff bases and benzyl
amines,10 as well as aromatic phosphines11 and phosphin-
ites.12,13 It is noteworthy that these nickelacyclic complexes
have all been prepared by oxidative addition of C−X bonds (X
= Br, Cl) to Ni(0) precursors and not via direct C−H
nickelation. To our knowledge, no nickelacyclic complex
(excluding pincer systems) has been prepared via C−H
metalation; this presents an opportunity for developing C−H
nickelation based routes to nickelacyclic systems.
We have elected to begin our studies by examining the C−H
functionalization of phosphinite ligands derived from phenol
and its substituted derivatives, because this approach would let
us capitalize on our experience in the synthesis and reactivities
of pincer complexes of nickel based on bis(phosphinites).14 An
important advantage of a phosphinite directing group in C−H
functionalization is its facile preparation from alcohols and
ClPR2, which would give access to a potentially large and
diverse family of substrates. In addition, a phosphinite moiety
can be removed readily by a number of simple workup
strategies, thus qualifying this strategy as a so-called “traceless”
functionalization.15 There are literature precedents for the use
of phosphinites in C−H functionalization using Ru,16 Rh,17 and
Pd,18 but none with Ni.
The present report describes the synthesis and full
characterization of the ligands R-C6H4OP(i-Pr2) (R = H
(1a), 4-OMe (1b), 4-Me (1c), 4-CO2Me (1d), 3-F (1e)) and
their bis-adducts trans-{R-C6H4OP(i-Pr2)}2NiBr2 (R = H (2a),
OMe (2b), Me (2c), CO2Me (2d)). Cyclonickelation of 1a
gave the complexes trans-{κ2P,C-C6H4OP(i-Pr)2}Ni(i-
Pr2POPh)Br (3a) and [{κ2P,C-C6H4OP(i-Pr)2}NiBr(μ-Br)]2
(4a), which were fully characterized and used in functionaliza-
tion tests with benzyl bromide to give 2-benzylphenol and its
phosphinated derivatives. Also described herein are the
influence of aryl substituents (OMe, Me, COOMe) on C−H
nickelation rates and site selectivity in the nickelation of 3-
fluorophenol.
a
Conditions: (i) R2PCl, NEt3, THF, room temperature, 1 h; (ii) 0.6
[(i-PrCN)NiBr2]n, 0.8 NEt3, toluene, 100 °C, 36 h; (iii) 2.0 [(i-
PrCN)NiBr2]n, 2.0 NEt3, toluene, 100 °C, 40 h; (iv) excess [(i-
PrCN)NiBr2]n, excess NEt3, toluene, 100 °C, 40 h; (v) 1a (1.0 equiv),
C6D6, room temperature, 5 min.
readily at room temperature with 1 equiv of 1a to give its
phosphinite adduct 3a, whereas heating the latter in the
presence of excess Ni precursor and base cleanly furnishes 4a.
This interconversion is significant for understanding the
cyclometalation pathway (vide infra).
The new complexes 3a and 4a have been characterized fully.
The 31P{1H} NMR spectrum of 4a shows a sharp singlet at 199
ppm, downfield of the corresponding signal for the free ligand
(149 ppm). Complex 3a showed the anticipated AB doublets at
ca. 185 and 152 ppm for the cyclometalated and non-
cyclometalated phosphinite moieties, respectively; the large
2JPP value of 325 Hz for these resonances is typical of
nonequivalent phosphinites in mutually trans positions.17,19
The 13C resonance for Cipso in 3a appeared as a doublet of
doublets at 132 ppm (2JCP = 14 and 29 Hz), whereas a complex
multiplet was observed for the corresponding signal in 4a.
X-ray diffraction studies carried out on single crystals of 3a
and 4a confirmed the solid-state structures of these complexes
(Figure 1). The Ni center in both complexes adopts a square-
planar geometry distorted by the five-membered metallacycle.
The different steric demands of the two phosphinite ligands in
3a also lead to structural distortions. For instance, the P atom
belonging to the noncyclometalated phosphinite moiety forms
larger cis angles relative to the corresponding angles involving
the P atom of the cyclometalated phosphinite moiety: 101 vs
83° for C−Ni−P and 92 vs 86° for P−Ni−Br. The same
phenomenon is observed in 4a: C1−Ni−P1 is much narrower
than C1−Ni−Br1 (ca. 98°). The trans angles in 4a and the
P1−Ni−P2 angle in 3a are not affected much (174−176°); the
latter is much larger than the corresponding angle in POCOP
complexes.20 On the other hand, the C−Ni−Br angle of 165°
in 3a is much smaller than the ideal value expected for a trans
angle, presumably due to steric repulsions between Br and the
noncyclometalated phosphinite.
RESULTS AND DISCUSSION
■
Synthesis and Characterization of Ortho-Nickelated
Complexes Derived from Phenol. Treating phenol with i-
Pr2PCl and NEt3 in THF gave the phosphinite ligand 1a (room
temperature, 1 h, 90%),18 which was then used for the synthesis
Inspection of the bond distances in 3a and 4a reveals
interesting observations on the impact of cyclometalation. In 3,
for example, the chelate effect of the cyclometalated moiety
6624
dx.doi.org/10.1021/om500938u | Organometallics 2014, 33, 6623−6632

Organometallics
Article
Figure 1. Structure diagrams for complexes 3a (left) and 4a (right). Thermal ellipsoids are shown at the 50% probability level. Hydrogen atoms are
omitted for clarity. Selected bond distances (Å) and angles (deg): Ni−C1= 1.935(2) (3a), 1.914(4) (4a); Ni−P1= 2.1359(5) (3a), 2.0953(10) (4a);
Ni−P2= 2.2510(5) (3a); Ni−Br1= 2.3664(3) (3a), 2.3641(7) (4a); Ni−Br1a = 2.3771(7) (4a); C1−Ni−Br1 = 164.92(5) (3a), 97.61(12) (4a);
C1−Ni−Br1a = 174.24(12) (4a); P−Ni−P = 172.97(2) (3a); C1−Ni−P1 = 82.96(5) (3a), 82.07(12) (4a); C1−Ni−P2 = 100.83(5) (3a); Br1a−
Ni−P1 = 92.62(3) (4a); Br1−Ni−P1 = 85.564(15) (3a), 176.19(4) (4a); Br1−Ni−P2 = 91.632(15) (3a); Br1−Ni−Br1a = 87.84(2) (4a).
Scheme 3. Proposed Ligand Dissociation and Exchange/Cyclometalation Process in the Presence of NEt3
results in a shorter Ni−P distance for P1 relative to P2 (2.14 vs
2.25 Å). An even shorter Ni−P distance is observed for the
cyclometalated moiety in 4a relative to 3a (2.10 vs 2.14 Å),
which can be attributed to two factors. First, P1 is trans from a
weaker ligand in 4a in comparison to that in 3a (Br < ArOPR2).
A second factor might be the decreased overall electron
donation to the Ni center when the nonmetalated phosphinite
moiety in 3a is replaced by a bridging Br in 4a: the shorter Ni−
P distance in the latter would thus compensate for this change.
This phenomenon would also rationalize the significantly
shorter Ni−C distance observed in 4a in comparison to 3a
(1.91 vs 1.94 Å).
Elucidation of C−H Nickelation Pathway. The path-
way(s) leading to complexes 3a and 4a were examined with the
objective of detecting intermediates and identifying the factors
influencing the C−H metalation step. Described below are our
attempts to intercept and characterize the species forming
initially on the path to cyclometalation.
the product as the bis(phosphinite) complex trans-(i-
Pr2POPh)2NiBr2 (2a). The structural parameters for this
square-planar compound are unexceptional and will be
discussed below along with the solid-state structures of its
substituted derivatives (vide infra).
To shed some light on the aforementioned fluxional process,
we examined the low-temperature NMR spectra of 2a
(CD2Cl2). The room-temperature 31P{1H} NMR spectrum
(Figure S1, Supporting Information) showed a broad singlet at
136 ppm (fwhm ≈ 760 Hz) that sharpened to a fine signal at
−68 °C (Figure S1). Similar observations have been reported
for the analogous complexes trans-(PR3)2NiBr2 (PR3 = i-
Pr2PMe, i-Pr2PPh),which also undergo fast ligand exchange.21
The upfield region of the room-temperature 13C{1H} NMR
spectrum of 2a (Figure S2, Supporting Information) also
showed a somewhat broad singlet for PCH(CH3)2, whereas
cooling to −68 °C led to appearance of the anticipated virtual
v
triplet (29 ppm, JPC = 12 Hz).
Stirring a toluene mixture of the ligand 1a and 0.5 equiv of
[(i-PrCN)NiBr2]n at room temperature led immediately to
formation of a dark brown solution displaying a broad 31P
singlet at 136 ppm, which is presumably due to a fluxional
process involving exchange of the phosphinite ligand. Single
crystals grown at −37 °C (deep yellow, 82% yield) were
subjected to X-ray diffraction studies that allowed us to identify
With the objective of examining the above ligand exchange
process under conditions relevant to the cyclometalation
reaction, we prepared a toluene sample of 2a (0.065 M)
containing 1.2 equiv of NEt3 and analyzed it by 31P{1H} NMR
spectroscopy, with and without heating. The predominant
signal in the ambient-temperature spectrum was the original
broad singlet (ca. 136 ppm), but the presence of NEt3 gave rise
6625
dx.doi.org/10.1021/om500938u | Organometallics 2014, 33, 6623−6632

Organometallics
Article
Figure 2. 31P{1H} NMR monitoring of a solution of 2a (50 mg, 78 μmol) and NEt3 (13 μL, 93.8 μmol) in toluene (1.2 mL) at 90 °C over 39 h.
to a second broad resonance at ca. 131 ppm as well as a sharp
resonance at 147 ppm attributed to free ligand 1a (Figure S3,
Supporting Information); the integration ratio for these signals
was approximately 20:1:1. We propose that the new broad
singlet at ca. 131 ppm represents the phosphinite-depleted
dimeric species [(i-Pr2POPh)BrNi(μ-Br)]2 and its NEt3 adduct
(i-Pr2POPh)(NEt3)NiBr2, which are in equilibrium with each
other and with 2a (Scheme 3). Given the much weaker L→Ni
binding force of NEt3 relative to that of most P-based ligands,
we believe it is unlikely that the substitution of the phosphinite
ligand in 2a is induced by NEt3; instead, we propose that 2a
undergoes ligand dissociation to generate a dimeric inter-
mediate that is then captured by NEt3, as shown in Scheme 3.
The spectrum of the toluene sample containing 2a and NEt3
discussed above remained virtually unchanged after 18 h at
room temperature, indicating that the equilibrium governing
the ligand exchange process is established at the time of mixing
and that the cyclometalation requires higher temperatures.
Heating this sample to 90 °C and monitoring by 31P{1H} NMR
allowed us to observe the gradual process of cyclometalation
(Figure 2). The original signals arising from the ligand
exchange process discussed above, namely the broad signals
at ca. 131 and 136 ppm and the sharp signal at 147 ppm, were
slowly replaced by the AB doublets due to the cyclometalated
species 3a. At the same time, the dark brown reaction mixture
faded gradually to a light yellow, and a white solid precipitated
(HBr·NEt3).
reaction mixture even when equimolar quantities of 1a and the
Ni precursor are employed. As above, we observe the gradual
conversion of 2a to the cyclometalated products 3a (AB
doublets at ∼185 and 152 ppm) and 4a (a singlet at ∼197
ppm) in the presence of NEt3. The preferential formation of 4a
over 3a is expected because of the 1:1 ratio of 1a to Ni
employed, but the observed broadness of the signals due to
2a−4a indicates that all of these species are in dynamic
exchange as long as free 1a is present in the reaction mixture.
Indeed, the only sharp signal detected in the process is the
singlet due to 4a (198 ppm), which appears at the very end of
the experiment as the sole P-bearing species. We conclude,
therefore, that cyclometalation is the only irreversible step in
this process (Scheme 3).
An important question that remains to answer is whether or
not the cyclometalation step involves the phosphinite-depleted
dimeric intermediate [(i-Pr2POPh)Ni(Br)(μ-Br)]2 postulated
above; in other words, is the observed phosphinite dissociation
equilibrium a required step for the cyclometalation? We carried
out the following experiments to shed some light on this issue.
Four NMR tubes were charged with 2a (89 μmol), NEt3 (107
μmol), and 0, 4, 8, and 16 equiv of 1a in toluene (500 μL); a
sealed capillary containing a toluene solution of PPh3 was
placed in the tubes to serve as the external standard. The
samples were heated to 90 °C for 12.5 h and analyzed by
31P{1H} NMR spectroscopy, with the following results: the
formation of 3a diminished in the presence of added ligand 1a
by 54%, 31%, 19%, and 8%, respectively, which suggests that
dissociation of a phosphinite from 2a is required for the
cyclonickelation step.
31P NMR spectroscopy was also used to monitor the gradual
formation of cyclometalated products in the reaction of 1a with
[(i-PrCN)NiBr2]n and NEt3 (molar ratio of 1:1:1; 90 °C;
Figure S4, Supporting Information). The predominant signal
observed during the initial stages of this reaction was the broad
singlet at ca. 136 ppm representing 2a, which indicates that this
bis(phosphinite) species is the main species present in the
We have not succeeded in isolating the dimeric intermediate
[(i-Pr2POPh)Ni(Br)(μ-Br)]2 postulated in Scheme 3. Similarly,
C−H palladation of closely related triaryl phosphite ligands are
also thought to involve such dimeric species,22 but none have
6626
dx.doi.org/10.1021/om500938u | Organometallics 2014, 33, 6623−6632

Organometallics
Article
been isolated during these reactions. On the other hand, the
complexes [(R3P)M(X)(μ-X)]2 (X = halide) are known for Pd
and Pt,23 whereas a search of the literature has revealed no
precedents for Ni, hinting that the latter might be inherently
unstable.
The new complexes 2b−d and 3b−d generated in the course
of the above study were characterized by comparing their NMR
spectral patterns to those of their analogues 2a and 3a. For
example, similarly to what was observed for 2a, a broad 31P
singlet was detected for 2b,c (136 ppm) and for 2d (131 ppm),
2
Influence of Aryl Substituents on Cyclonickelation.
C−H metalation of aromatic substrates by MXn can proceed
through different mechanisms,24 including the classical route
involving successive steps of oxidative addition to give a
hydrido aryl intermediate followed by reductive elimination of
HX. While such a redox process seems a priori unlikely with a
Ni(II) precursor, it is difficult to rule out this scenario
experimentally. Another distinct possibility would be a so-called
electrophilic (nonredox) process involving an initial binding of
the C (or C−H) fragment followed by removal of H+ by X−.
The latter process can take place in sequence or in a concerted
manner, and it can be considered a σ-bond metathesis if there is
little or no polarization of the C−H and M−X moieties at the
transition state. Such an electrophilic mechanism is also difficult
to establish unambiguously, but its likelihood can be evaluated
when the impact of electronic factors on C−H nickelation rates
is known. We have therefore examined the relative rates of C−
H nickelation in substituted phenols in order to evaluate the
electronic impact of substituents on cyclometalation rates, as
described below.
The arenols 4-methoxyphenol, p-cresol, and methyl 4-
hydroxybenzoate were used to prepare and isolate in 78−97%
yields the corresponding phosphinites i-Pr2PO(4-R-C6H4) (R=
OMe (1b), Me (1c), CO2Me (1d)), as described above for the
parent ligand 1a (THF/NEt3, room temperature, 1 h). The
31P{1H} NMR spectra of these ligands showed a singlet at ca.
150 ppm, characteristic of i-Pr2POAr.18,19 In a manner
analogous to the synthesis of 2a, the new ligands were then
treated with 0.5 equiv of [(i-PrCN)NiBr2]n at room temper-
ature to give the bis(phosphinite) complexes trans-(i-
Pr2POAr)2NiBr2 (2b−d) (Scheme 4).
whereas AB doublets featuring large JPP values were observed
in the 31P{1H} NMR spectra of 3b−d (∼152 and 185 ppm; 2JPP
≈ 325 Hz). Single crystals were also grown for 2b−d and
subjected to X-ray diffraction studies. Figure 3 shows structure
diagrams for 2a,c, and Table 1 gives selected structural
parameters for 2a−d (see Figure S6 in the Supporting
Information for structure diagrams of 2b,d). Complexes 2a,b
display an inversion center at the Ni atom, and a nearly ideal
square-planar geometry is seen for 2a,b,d, whereas 2c shows an
unexpectedly large distortion in the Br−Ni−Br angle (166°).
The Ni−P and Ni−Br distances in 2a−d, 2.22−2.24 and 2.29−
2.30 Å, respectively, are somewhat shorter than the
corresponding distances in 3a (2.25 and 2.37 Å).
Question of Site Selectivity in Cyclonickelation. The
cyclometalation reactions discussed to this point have involved
phosphinite ligands derived from either phenol or its para-
substituted derivatives, all of which can give only one product
of monometalation. The same scenario should normally hold
for ortho-substituted analogues, whereas R2POAr derived from
meta-substituted arenols 3-R′-C6H4OH can, in principle, result
in two different cyclonickelation products depending on which
C−H is metalated: that situated between the OPR2 and R′ or
that situated ortho to the OPR2 and para to R′. We have
addressed this question briefly by studying the cyclonickelation
of 3-fluorophenol, as described below. The choice of F as
substituent was predicated by its similar steric properties
relative to H, which should ensure that electronic effects are the
dominant factor in site selectivity.
The ligand 3-F-C6H4OP(i-Pr)2 (1e) was prepared similarly
to 1a−d described above and was treated with [(i-PrCN)-
NiBr2]n and NEt3 (0.5 and 1.2 equiv, respectively) at 100 °C in
toluene for 25 h (Scheme 5). 31P{1H} NMR analysis of the
reaction mixture at t = 25 h showed the emergence of two sets
of AB resonances assigned to the cyclonickelated species
analogous to 3a (Figure S7, Supporting Information). The
major resonances appeared at 155.5 and 186.5 ppm (JPP = 325
Hz) and have been assigned to isomer 3ep, wherein the
nickelated carbon atom is para to F. The minor AB resonances
(2JPP = 341 Hz) appearing at ca. 184 ppm (4JPF = 2 Hz) and ca.
156 ppm (4JPF = 32 Hz) have been assigned to the isomer 3eo,
wherein the nickelated carbon atom is ortho to F.
Scheme 4. Synthesis of 2b−d
In addition to the AB resonances noted above, the spectrum
shows two broad singlets assigned to the free ligand 1e (150
ppm) and to the bis(phosphinite) species trans-{3-F-C6H4OP-
(i-Pr)2}2NiBr2 (2e) (139 ppm); the presence of these signals
indicates that the C−H nickelation reaction is incomplete. The
19F NMR analysis of the final mixture confirmed the presence
of four F-bearing species, and integration of 19F and 31P{1H}
signals indicated ∼65% cyclonickelation and a 5.6:1 ratio for
the cyclonickelation products 3ep and 3eo. The greater
preference for metalation of the C−H moiety para to F in 3-
F-C6H4OP(i-Pr)2 parallels the 6:1 selectivity reported for Pd-
catalyzed acetoxylation of 2-(3-fluorophenyl)pyridine at the
position para to F.27
Toluene solutions of 2b−d (0.16 mmol in 382 μL; 0.042 M)
containing 10 equiv of NEt3 were then heated to 100 °C, and
formation of the corresponding cyclometalated complexes 3b−
d was monitored by 31P NMR spectroscopy.25 Integration of
the resulting spectra allowed us to establish the aryl
substituents’ influence on nickelation (Figure S5, Supporting
Information): after ca. 5 h, cyclometalation had progressed to a
greater extent for complex 3b (39%) relative to 3c (32%) and
3d (22%). These results are consistent with an electrophilic
cyclonickelation mechanism for this family of phosphinite
ligands. A similar trend (OMe > Me > CO2Me) was also found
for the impact of the 4-R substituent in the nickelation of
resorcinol-based bis(phosphinite) ligands to give the corre-
sponding POCOP-type pincer complexes of Ni(II).26
Ortho Derivatization. As mentioned earlier, a number of
metallacyclic complexes of nickel have been prepared by
oxidative addition of C−X moieties to zerovalent Ni
precursors.10−13 It is also known that the Ni−Ar moiety in
6627
dx.doi.org/10.1021/om500938u | Organometallics 2014, 33, 6623−6632

Organometallics
Article
Figure 3. Structure diagrams for complexes 2a (left) and 2c (right). Thermal ellipsoids are shown at the 50% probability level, and hydrogen atoms
are omitted for clarity. Selected structural parameters are given in Table 1.
Table 1. Selected Bond Distances (Å) and Angles (deg) for Complexes 2a−d
compd
Ni−P1
Ni−P2
Ni−Br1
Ni−Br2
P−Ni−P
Br−Ni−Br
P1−Ni−Br1
2a
2.243(1)
2.238(1)
2.225(1)
2.230(1)
2.297(1)
2.298(1)
2.303(1)
2.290(1)
180.0
180.0
88.81(1)
88.60(2)
87.23(1)
89.16(2)
a
2b
180.0
180.0
2c
2.240(1)
2.228(1)
2.301(1)
2.292(1)
175.90(2)
179.83(2)
166.63(1)
179.79(2)
a
2d
a
Values given are for molecule 1.
Scheme 5. Cyclonickelation of 1e
Scheme 6. Postulated Pathways for Benzylation of 3a
some of these complexes is fairly reactive, undergoing insertion
of CO, SO2, or alkynes28 or initiating polymerization of
olefins.29 We have briefly investigated the reactivity of the
newly created C−Ni bonds in the cyclometalated complexes 3a
and 4a to establish the feasibility of developing a viable
methodology for functionalizing arenols.30
6628
dx.doi.org/10.1021/om500938u | Organometallics 2014, 33, 6623−6632

Organometallics
Article
The first tests were done using complex 3a, as follows. A J.
Young NMR tube containing an equimolar mixture of 3a and
benzyl bromide in 0.5 mL of toluene (0.08 M) was heated to
100 °C for 84 h, and the final mixture was subjected to 31P{1H}
NMR and GC/MS analysis. The NMR analysis confirmed the
complete consumption of 3a, and GC/MS showed the
presence of the starting ligand 1a (m/z 210), its benzylated
derivative 1a-Bn (m/z 300), and the oxidized forms of these
phosphinites (m/z 226 and 316, respectively). Interestingly, the
ratio of benzylated to nonbenzylated fractions was greater than
1:1 (∼1.25:1.0), which implies that the putative bis-
(phosphinite) species formed as a result of the initial
benzylation reacts further to cyclometalate the monodentate
phosphinite moiety, as shown in Scheme 6 (species 3a′ and
2a″). It should be emphasized that we have no evidence for the
formation of products featuring benzylation at both ortho sites.
The benzylation reaction was also conducted with the
dimeric species 4a, which has a 1:1 ratio of Ni to phosphinite (3
equiv of benzyl bromide; toluene, 90 °C; 36 h). The final
reaction mixture was subjected to a hydrolytic workup in the
presence of HClaq, followed by column chromatography (SiO2)
to give 2-benzylphenol in 47% isolated yield (Scheme 7). The
Ortho nickelation of 3-F-C6H4OP(i-Pr)2 allowed us to
establish that nickelation is favored at the C−H moiety para
with respect to the fluoro substituent. Further studies are
needed to determine the site selectivity of C−H nickelation
with other substituents. Benzylation of the ipso-C atoms in 3a
and 4a with benzyl bromide provided proof of concept for the
feasibility of the envisaged areneol functionalization strategy,
but much work remains to be done to expand the scope of
functionalization and to identify reaction conditions under
which the process can be catalytic in both Ni and
chlorophosphine.
EXPERIMENTAL SECTION
■
General Considerations. Unless otherwise indicated, all manip-
ulations were carried out under a nitrogen atmosphere using standard
Schlenk techniques and an inert-atmosphere box. Solvents were dried
by passage over activated alumina, collected under nitrogen, and stored
over 4 Å molecular sieves. Triethylamine was dried by distillation over
CaH2. The synthesis and characterization of ligands 1a,c has been
reported by Bedford et al.;18 a slightly modified version of this
procedure, described below, was used to prepare 1b,d,e. Synthesis of
the nickel precursor [(i-PrCN)NiBr2]n used throughout this study has
been described previously.19 All other reagents were purchased from
Sigma-Aldrich and were used without further purification.
Scheme 7. Benzylation of 4a
The NMR spectra were recorded at 400 or 500 MHz (1H), 100.56
MHz (13C), and 161.9 MHz (31P). Chemical shift values are reported
in ppm (δ) and referenced internally to the residual solvent signals (1H
and 13C: 7.26 and 77.16 ppm for CDCl3; 7.16 and 128.06 ppm for
C6D6; 5.32 and 53.84 ppm for CD2Cl2) or externally (31P, H3PO4 in
D2O, δ 0); J values are given in Hz. The elemental analyses were
́
performed by the Laboratoire d’Analyze Elem
́ ́
entaire, Departement de
chimie, Universite de Montreal.
́
́
(3-F-C6H4O)P(i-Pr)2 (1e). Dropwise addition of ClP(i-Pr)2 (490
μL, 3.0 mmol) to a solution of 3-fluorophenol (271 μL, 3.0 mmol) and
NEt3 (460 μL, 3.5 mmol) in THF (25 mL) led to the appearance of a
white precipitate. The reaction mixture was stirred at room
temperature for 1 h and evaporated, and the solid residues were
extracted with hexane (2 × 25 mL). Evaporation under vacuum gave
the crude product as a colorless oil (543 mg, 78%), which was shown
to be greater than 98% pure by NMR spectroscopy. This material was
used without further purification in subsequent experiments. 1H NMR
(400 MHz, 20 °C, C6D6): δ 0.91 (dd, JHP = 15.90, JHH = 7.23, 6H,
CH(CH3)2), 1.06 (dd, JHP = 10.65, JHH = 7.0, 6H, CH(CH3)2), 1.71
(hd, JHH = 7.08, JHP = 2.75, 2H, PCH(CH3)2), 6.51 (m, 1H, HAr), 6.85
(m, 1H, HAr), 6.92 (m, 1H, HAr), 7.03 (m, 1H, HAr). 19F NMR (376
MHz, 20 °C, C6D6): δ −111.56 (m). 31P{1H} NMR (162 MHz, 20
°C, CDCl3): δ 151.14 (s). 13C{1H} NMR (101 MHz, 20 °C, CDCl3):
δ 17.03 (d, JCP = 8.56, 2C, CH3), 17.71 (d, JCP = 20.5, 2C, CH3), 28.52
(d, JCP = 18.42, 2C, PCH(CH3)2), 106.48 (dd, JFC = 24.08, JPC = 11.50,
1C, CHAr), 108.71 (d, JFC = 21.26, 1C, CHAr), 114.50 (dd, JFC = 2.97,
JPC =11.0, 1C, CHAr), 130.47 (d, JFC = 9.98, 1C, CHAr), 161.35 (vt, JPC
= JFC =10.45, 1C, CArOP), 163.99 (d, JFC = 245.6, 1C, F-CAr). Anal.
Calcd for C12H18FOP (228.24): C, 63.15; H, 7.95. Found: C, 63.43;
H, 8.20.
(4-OMe-C6H4O)P(i-Pr)2 (1b). The procedure described above for
the preparation of 1e was used here to give 1b as a colorless oil (1.87
g, 97%). 1H NMR (400 MHz, 20 °C, CDCl3): δ 1.13 (dd, JHP = 15.80,
JHH = 7.25, 6H, CH(CH3)2), 1.21 (dd, JHP = 10.70, JHH = 6.98, 6H,
CH(CH3)2), 1.92 (hd, JHH = 7.09, JHP = 2.17, 2H, PCH(CH3)2), 3.74
(s, 3H, OMe), 6.81 (d, JHH = 6.80, 2H, HAr), 7.05 (dd, JHH = 8.70, JPH
= 1.56, 2H, HAr). 31P{1H} NMR (162 MHz, 20 °C, CDCl3): δ 150.6
(s). 13C{1H} NMR (101 MHz, 20 °C, CDCl3): δ 16.97 (d, JCP = 8.53,
2C, CH3), 17.74 (d, JCP = 20.27, 2C, CH3), 28.26 (d, JCP = 17.86, 2C,
PCH(CH3)2), 55.40 (s, 1C, OMe), 114.31 (s, 2C, CHAr), 119.25 (d,
JPC =9.53, 2C, CHAr), 153.21 (d, JPC =8.86, 1C, CAr), 154.36 (s, 1C,
CAr). Anal. Calcd for C13H21O2P (240.28): C, 64.98; H, 8.81. Found:
C, 64.90; H, 8.94.
identity of this product was confirmed by GC/MS (m/z 184)
and by 1H and 13C NMR (e.g., a singlet at 3.91 ppm
corresponding to the CH2Ph proton and a deshielded singlet at
4.83 ppm for OH). These results demonstrate the feasibility of
Ni-promoted ortho functionalization of phenol through its i-
Pr2P phosphinite derivative.
Monitoring the reaction of 4a with PhCH2Br by 31P{1H}
NMR spectroscopy provided further support for the path-
way(s) postulated in Scheme 6. Thus, we observed that over
time the signal due to 4a (s, 199 ppm) was replaced by two
broad singlets at 134 and 133 ppm, which can be assigned to
species 2a′ and 2a″ shown in Scheme 6, and three pairs of AB
doublets (2JPP = 324 Hz) at ca. 183 and ca. 149−151 ppm. Of
these, the more intense set of signals at 183.4 and 149.3 ppm is
tentatively assigned to 3a′, while the less intense sets are likely
due to closely related products bearing different OAr moieties.
CONCLUSION
■
The results reported above establish that it is feasible to ortho
nickelate the aryl phosphinites i-Pr2P(OAr) using a simple
Ni(II) precursor. The isolation and full characterization of the
two nickelacycle compounds 3a and 4a has allowed us to study
their structural and spectroscopic properties. We have also
determined the conditions favoring the formation of one or the
other of these complexes and investigated the importance of
aryl substituents on the C−H nickelation pathway (OMe > Me
> COOMe). The latter studies point to an electrophilic C−H
nickelation taking place with a mono(phosphinite) intermedi-
ate generated in situ through ligand dissociation. Our
observations also indicate that phosphinite dissociation favors
the C−H nickelation process.
6629
dx.doi.org/10.1021/om500938u | Organometallics 2014, 33, 6623−6632

Organometallics
Article
(4-COOMe-C6H4O)P(i-Pr)2 (1d). The procedure described above
for the preparation of 1e was used here to give 1d as a colorless oil
(0.90 g, 87%). 1H NMR (400 MHz, 20 °C, CDCl3): δ 1.04−1.09 (m,
6H, CH(CH3)2), 1.11−1.15 (m, 6H, CH(CH3)2), 1.92 (m, 2H,
PCH(CH3)2), 3.85 (m, 3H, OMe), 7.13 (m, 2H, HAr), 7.94 (m, 2H,
HAr). 31P{1H} NMR (162 MHz, 20 °C, CDCl3): δ 150.4 (s). 13C{1H}
NMR (101 MHz, 20 °C, CDCl3): δ 17.01 (d, JCP = 8.32, 2C, CH3),
17.71 (d, JCP = 20.20, 2C, CH3), 28.37 (d, JCP = 17.81, 2C,
PCH(CH3)2), 51.90 (s, 1C, OMe), 118.15 (d, JPC = 11.13 2C, CHAr),
123.40 (s, 1C, CAr), 131.5 (s, 2C, CHAr), 163.48 (d, JPC = 8.42, 1C,
CO or CArOP), 166.84 (s, 1C, CO or CArOP). Anal. Calcd for
C14H21O3P (268.29): C, 62.67; H, 7.89. Found: C, 62.59; H, 7.91.
trans-{i-Pr2P(OPh)}2NiBr2 (2a). [(i-PrCN)NiBr2]n (1.9 mmol, 547
mg) was added to a solution of 1a (3.81 mmol, 800 mg) in toluene (5
mL), and the resulting brown solution was stirred for 2 h at room
temperature. Filtration and evaporation gave the target compound as a
dark brown solid (995 mg, 82%). Brown single crystals were obtained
through slow crystallization in toluene (2 days at −37 °C). This
complex is fairly air stable over short periods, but aerobic
decomposition sets in after 1 week to give an NMR-silent beige
trans-(κ2P,C-i-Pr2POPh)(i-Pr2POPh)NiBr (3a). [(i-PrCN)NiBr2]n
(1.25 mmol, 360 mg) and NEt3 (1.66 mmol, 232 μL) were added to a
solution of 1a (500 mg, 2.08 mmol) in toluene (20 mL). The resulting
brown solution was stirred over 48 h at 100 °C and evaporated, and
the solid residues were extracted with toluene (2 × 30 mL).
Evaporation of the combined extracts gave 3a as a yellow solid (540
mg, 93%), which was found to be greater than 98% pure by NMR
spectroscopy; this material was used in subsequent experiments
without further purification. Single crystals were obtained from a
1
saturated hexane solution at −37 °C. H NMR (400 MHz, 20 °C,
C6D6): δ 1.27 (vt, JHP = JHH = 6.35, 6H, CH(CH3)2), 1.30 (dd, JHP
=
4.56, JHH = 7.03, 6H, CH(CH3)2), 1.51 (dd, JHP = 16.84, JHH = 7.21,
6H, CH(CH3)2), 1.56 (dd, JHP = 16.03, JHH = 7.35, 6H, CH(CH3)2),
2.49 (m, 2H, PCH(CH3)2), 2.81 (m, 2H, PCH(CH3)2), 6.51 (t, JHH
=
7.47, 1H, HAr), 6.67 (t, JHH = 7.40, 1H, HAr), 6.80−6.87 (m, 2H, HAr),
6.93 (t, JHH = 7.65, 2H, HAr), 7.57 (d, JHH = 8.49, 2H, HAr), 7.64 (d,
JHH = 7.76, 1H, HAr). 13C{1H} NMR (101 MHz, 20 °C, CDCl3): δ
17.12 (s, 2C, CH3), 17.87 (s, 2C, CH3), 18.79 (d, JCP = 3.58, 2C,
CH3), 20.52 (d, JCP = 4.68, 2C, CH3), 28.63 (dd, JCP = 2.47, JCP
=
23.79, 2C, PCH(CH3)2), 29.94 (dd, JCP = 2.82, JCP = 17.61, 2C,
PCH(CH3)2), 110.35 (d, JPC =13.53, 1C, CHAr), 120.0 (d, JCP = 6.14,
2C, CHAr), 120.55 (m, 1C, CHAr), 122.51 (s, CHAr), 126.46 (s, 1C,
CHAr), 128.91 (s, 2C, CHAr), 132.0 (dd, JCP = 14.30, JCP = 29.37, 1C,
Ni-CAr), 142.25 (d, JCP = 11.04, 1C, CHAr), 154.73 (d, JCP = 4.62, 1C,
OCAr), 168.38 (dd, JCP = 4.33, JCP = 16.24, 1C, OCAr). 31P{1H} NMR
(162 MHz, 20 °C, C6D6): δ 151.86 (d (AB), JPP = 325, 1P), 184.66 (d
(AB), JPP = 325, 1P). Anal. Calcd for C24H37BrNiO2P2 (558.09): C,
51.65; H, 6.68. Found: C, 51.94; H, 6.71.
1
powder. H NMR (500 MHz, 20 °C, CD2Cl2): δ 1.42 (d, JHH = 7.15,
12H, CH(CH3)), 1.54 (d, JHH = 7.29, 12H, CH(CH3)), 2.79 (h, JHH
=
7.19 4H, CH(CH3)), 7.11 (tt, JHH = 7.15, JHH = 1.02 2H, Hpara), 7.37
(dd, JHH = 8.64, JHH = 7.41, 4H, Hmeta), 7.66 (dm, JHH = 7.69, 4H,
Hortho). 1H NMR (500 MHz, −68 °C, CD2Cl2): δ 1.37 (dtv, JHH = 7.25,
JHP = 7.17, 12H, CH(CH3)), 1.47 (dtv, JHH = 7.83, JHP = 7.75, 12H,
CH(CH3)), 2.70 (m, 4H, CH(CH3)), 7.10 (t, JHH = 7.37, 2H, Hpara),
7.37 (dd, JHH = 8.3, JHH = 7.66, 4H, Hmeta), 7.66 (d, JHH = 8.01, 4H,
Hortho). 13C{1H} NMR(125 MHz, 20 °C, CD2Cl2): δ 18.25 (s, 4C,
CH3), 19.70 (s, 4C, CH3), 30.08 (s, 4C, PCH(CH3)2), 120.23 (s, 4C,
CHAr), 122.96 (s, 2C, CHAr), 129.30 (s, 4C, CHAr), 155.28 (s, 2C,
CArOP). 13C{1H} NMR (125 MHz, −68 °C, CD2Cl2): δ 17.63 (s, 4C,
CH3), 19.12 (s, 4C, CH3), 29.03 (vt, JPC = 11.95, 4C, PCH(CH3)2),
119.20 (s, 4C, CHAr), 122.26 (s, 2C, CHAr), 128.80 (s, 4C, CHAr),
154.26 (s, 1C, CArOP). 31P {1H} NMR (201 MHz, 20 °C, CD2Cl2) ; δ
135.8 (bs, 1P). 31P{1H} NMR (201 MHz, −68 °C, CD2Cl2): δ 136.2
(s, 1P). Anal. Calcd for C24H38Br2NiO2P2 (639.01): C, 45.11; H, 5.99.
Found: C, 45.19; H, 5.92.
[(κ2P,C-i-Pr2POPh)NiBr(μ-Br)]2, (4a). [(i-PrCN)NiBr2]n (5.45 g,
19 mmol) and NEt3 (2.64 mL, 19 mmol) were added to a solution of
1a (2 g, 9.5 mmol) in toluene (50 mL). The resulting brown solution
was stirred over 40 h at 100 °C to give a green mixture, which was
evaporated, and the solid residues were extracted with toluene (2 × 50
mL). The extracted solution was once again evaporated to dryness and
washed with hexane (25 mL) to give 4a as a yellow powder (2.3 g,
70%). Single crystals were obtained from a saturated toluene/hexane
solution at −37 °C. 1H NMR (500 MHz, 20 °C, CD2Cl2): δ 1.37 (dd,
JHH = 6.80, JHP = 14.60, 24H, CH(CH3)), 1.57 (dd, JHH = 6.00, JHP
=
trans-{i-Pr2P(4-OMe-C6H4O)}2NiBr2 (2b). The procedure de-
scribed above for the preparation of 2a was used to give 2b as a
dark orange solid (458 mg, 80%). 1H NMR (400 MHz, 20 °C,
CDCl3): δ 1.42 (m, 24H, CH(CH3)), 2.81 (m, 4H, CH(CH3)), 3.82
(s, 6H, OMe), 6.88 (m, 4H, HAr), 7.51 (m, 4H, HAr). 13C{1H} NMR
(101 MHz, 20 °C, CDCl3): δ 18.13 (s, 4C, CH3), 19.43 (s, 4C, CH3),
29.73 (s, 4C, PCH(CH3)2), 55.63 (s, 2C, OMe), 114.02 (s, 4C, CHAr),
120.82 (s, 4C, CHAr), 148.73 (s, 2C, OCAr), 155.07 (s, 2C, CArOP).
31P{1H} NMR (162 MHz, 20 °C, CDCl3): δ 136.0 (bs, 1P). Anal.
Calcd for C26H42Br2NiO4P2 (699.06): C, 44.67; H, 6.06. Found: C,
44.71; H, 6.14.
17.37, 24H, CH(CH3)), 2.35 (m, 4H, CH(CH3)), 6.59 (m, 4H, HAr),
6.92 (m, 2H, HAr), 7.27 (m, 2H, HAr). 13C{1H} NMR (125 MHz, 20
°C, CD2Cl2): δ 16.69 (s, 4C, CH3), 18.00 (s, 4C, CH3), 28.90 (d, JCP
=
26.60, 4C, PCH(CH3)2), 110.23 (d, JCP = 13.88, 2C, CHAr), 121.02 (s,
2C, CHAr), 126.95 (s, 2C, CHAr), 128.56 (bm, 2C, NiCAr), 140.71 (s,
2C, CHAr), 166.58 (d, JCP = 12.02, 2C, OCAr). 31P{1H} NMR (201
MHz, 20 °C, CD2Cl2): δ 199.1 (s, 1P). Anal. Calcd for
C24H36Br2Ni2O2P2 (695.68): C, 41.44; H, 5.22. Found: C, 42.06; H,
5.22.
Functionalization of Phenol to 2-Benzylphenol. Benzyl
bromide (2.84 mmol, 338 μL) was added to a solution of 4a (0.95
mmol, 660 mg) in toluene (25 mL), and the resulting mixture was
stirred for 36 h at 90 °C. The final mixture was added to HClaq (100
mL, 2.5 M) and extracted with CH2Cl2 (3 × 50 mL). The combined
organic phases were dried over MgSO4, filtered, and evaporated under
vacuum, and the residue obtained was purified on a silica gel column
(CHCl3/hexane 1/1) to give 2-benzylphenol (Rf = 0.1) as a white
solid (47%, 164 mg). 1H NMR (400 MHz, 20 °C, CDCl3): δ 3.91 (s,
2H, CH2), 4.83 (s, 1H, OH), 6.63 (d, JHH = 7.81, 1H, CHAr), 6.82 (t,
JHH = 7.14, 1H, CHAr), 7.03 (m, 2H, CHAr), 7.14−7.21 (m, 5H, CHAr).
13C NMR (125 MHz, 20 °C, CDCl3): δ 36.31 (s, 1C, CH2), 115.80 (s,
1C, CHAr), 121.06 (s, 1C, CHAr), 126.38 (s, 1C, CHAr), 127.18 (s, 1C,
Cq), 127.86 (s, 1C, CHAr), 128.68 (s, 2C, CHAr), 128.80 (s, 2C, CHAr),
131.04 (s, 1C, CHAr), 140.03 (s, 1C, Cq), 153.66 (s, 1C, Cq). GC-MS:
m/z 184 (M+).
Crystal Structure Determinations. The crystallographic data for
compounds 2a,e and 3a were collected on a Bruker Microstar
generator (micro source) equipped with Helios optics, a Kappa
Nonius goniometer, and a Platinum135 detector. The crystallographic
data for complexes 4a and 2c,d were collected on a a Bruker APEX II
instrument equipped with a Incoatec I\muS Microsource and a Quazar
MX monochromator. Cell refinement and data reduction were done
trans-{i-Pr2P(4-Me-C6H4O)}2NiBr2 (2c). The procedure described
above for the preparation of 2a was used to give 2c as a dark orange
solid (800 mg, 80%). 1H NMR (400 MHz, 20 °C, CDCl3): δ 1.40 (d,
JHH = 7.06, 12H, CH(CH3)), 1.52 (d, JHH = 7.19, 12H, CH(CH3)),
2.33 (s, 6H, Me), 2.75 (h, JHH = 7.12 4H, CH(CH3)), 7.11 (d, JHH
=
8.19, 4H, HAr), 7.50 (d, JHH = 8.39, 4H, Hortho). 31P{1H} NMR (162
MHz, 20 °C, CDCl3): δ 136.0 (bs, 1P). Anal. Calcd for
C26H42Br2NiO2P2 (667.06): C, 46.81; H, 6.35. Found: C, 47.08; H,
6.44.
trans-{i-Pr2P(4-COOMe-C6H4O)}2NiBr2 (2d). The procedure
described above for the preparation of 2a was used to give 2d as a
dark orange solid (504 mg, 91%). 1H NMR (300 MHz, 20 °C,
CDCl3): δ 1.40 (d, JHH = 6.43, 12H, CH(CH3)), 1.55 (d, JHH = 6.41,
12H, CH(CH3)), 2.76 (h, JHH = 7.13 4H, CH(CH3)), 3.92 (s, 6H,
OMe), 7.63 (d, JHH = 7.63, 4H, HAr), 8.04 (d, JHH = 8.67, 4H, Hortho).
13C{1H} NMR (75 MHz, 20 °C, CDCl3): δ 18.20 (s, 4C, CH3), 19.70
(s, 4C, CH3), 29.90 (s, 4C, PCH(CH3)2), 52.16 (s, 2C, OMe), 119.83
(s, 4C, CHAr), 124.76 (s, 2C, CAr), 131.09 (s, 4C, CHAr), 158.86 (s,
2C, CArOP), 166.71 (s, 2C, CO). 31P{1H} NMR (162 MHz, 20 °C,
CDCl3): δ 139.9 (bs, 1P). Anal. Calcd for C28H42Br2NiO3P2. C7H8
(847.22): C, 49.62; H, 5.95. Found: C, 49.28; H, 5.89.
6630
dx.doi.org/10.1021/om500938u | Organometallics 2014, 33, 6623−6632

Organometallics
Article
using SAINT.31 An empirical absorption correction, based on the
multiple measurements of equivalent reflections, was applied using the
program SADABS.32 The space group was confirmed by the XPREP
routine33 in the program SHELXTL.34 The structures were solved by
direct methods and refined by full-matrix least squares and difference
Fourier techniques with SHELX-97.35 All non-hydrogen atoms were
refined with anisotropic displacement parameters. Hydrogen atoms
were set in calculated positions and refined as riding atoms with a
common thermal parameter.
(5) (a) Yoshikai, N.; Matsumoto, A.; Norinder, J.; Nakamura, E.
Angew. Chem., Int. Ed. 2009, 48, 2925. (b) Norinder, J.; Matsumoto,
A.; Yoshikai, N.; Nakamura, E. J. Am. Chem. Soc. 2008, 130, 5858.
(c) Wen, J.; Zhang, J.; Chen, S.-Y.; Li, J.; Yu, X.-Q. Angew. Chem., Int.
Ed. 2008, 47, 8897. (d) Liu, W.; Cao, H.; Lei, A. Angew. Chem., Int. Ed.
2010, 49, 2004.
(6) (a) Yoshikai, N. Synlett 2011, 8, 1047. (b) Gao, K.; Yoshikai, N.
Chem. Commun. 2012, 48, 4305. (c) Lee, P.-S.; Fujita, T.; Yoshikai, N.
J. Am. Chem. Soc. 2011, 133, 17283. (d) Gao, K.; Yoshikai, N. J. Am.
Chem. Soc. 2013, 135, 9279. (e) Gao, K.; Yoshikai, N. J. Am. Chem. Soc.
2011, 133, 400. (f) Gao, K.; Lee, P.-S.; Fujita, T.; Yoshikai, N. J. Am.
Chem. Soc. 2010, 132, 12249.
(7) (a) Shacklady-McAtee, D. M.; Dasgupta, S.; Watson, M. P. Org.
Lett. 2011, 13, 3490. (b) Ogata, K.; Atsuumi, Y.; Shimada, D.;
Fukuzawa, S. Angew. Chem., Int. Ed. 2011, 50, 5896. (c) Shiota, H.;
Ano, Y.; Aihara, Y.; Fukumoto, Y.; Chatani, N. J. Am. Chem. Soc. 2011,
133, 14952. (d) Kanyiva, K. S.; Nakao, Y.; Hiyama, T. Angew. Chem.,
Int. Ed. 2007, 46, 8872. (e) Nakao, Y.; Kanyiva, K. S.; Hiyama, T. J.
Am. Chem. Soc. 2008, 130, 2448. (f) Tobisu, M.; Hyodo, I.; Chatani,
N. J. Am. Chem. Soc. 2009, 131, 12070. (g) Aihara, Y.; Chatani, N. J.
Am. Chem. Soc. 2013, 135, 5308. (h) Song, W.; Lackner, S.;
Ackermann, L. Angew. Chem., Int. Ed. 2014, 53, 2477.
ASSOCIATED CONTENT
■
S
* Supporting Information
Tables, figures, and CIF files giving crystal data and collection/
refinement parameters, structural diagrams for complexes 2b,d,
various NMR spectra, and crystallographic data. This material is
available free of charge via the Internet at http://pubs.acs.org.
Complete details of the X-ray analyses reported herein have
also been deposited at The Cambridge Crystallographic Data
Centre (CCDC 1012836 (2a), 1012835 (2c), 1012832 (2d),
1012834 (2e), 1012833 (3a), 1012831 (4a)). These data can
be obtained free of charge via www.ccdc.cam.ac.uk/data_
request/cif, by emailing data_request@ccdc.cam.ac.uk, or by
contacting The Cambridge Crystallographic Data Centre, 12,
Union Road, Cambridge CB2 1EZ, U.K. (fax +44 1223
336033).
(8) Kleiman, J. P.; Dubeck, M. J. Am. Chem. Soc. 1963, 85, 1544.
(9) Zargarian, D. Coord. Chem. Rev. 2002, 233, 157.
(10) (a) Ceder, R. M.; Granell, J.; Muller, G. J. Chem. Soc., Dalton
Trans. 1998, 1047. (b) Ceder, R. M.; Granell, J.; Muller, G.; Font-
Bardia, M.; Solans, X. Organometallics 1995, 14, 5544. (c) Ceder, R.
M.; Granell, J.; Muller, G.; Font-Bardía, M.; Solans, X. Organometallics
1996, 15, 4618.
(11) Muller, G.; Panyella, D.; Rocamora, M.; Sales, J.; Font-Bardía,
M.; Solans, X. J. Chem. Soc., Dalton Trans. 1993, 2959.
(12) Ruhland, K.; Obenhuber, A.; Hoffmann, S. D. Organometallics
2008, 27, 3482.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail for D.Z.: zargarian.davit@umontreal.ca.
Notes
The authors declare no competing financial interest.
(13) Cam
by insertion of ArNC or CO into the Ni-bimetallic species trans-
(Me3P)BrNi(μ2-η3:η1-CH2-o-C6H4)NiBr(PMe3)2: (a) Cam
pora, J.;
Gutierrez, E.; Monge, A.; Poveda, M. L.; Ruiz, C.; Carmona, E.
Organometallics 1993, 12, 4025. (b) Campora, J.; Gutierrez, E.; Monge,
́
pora et al. have also reported imidoyl complexes prepared
́
ACKNOWLEDGMENTS
■
The authors are grateful to the NSERC of Canada for a
Discovery Grant to D.Z., the Universite
Green Chemistry and Catalysis, and FQRNT for graduate
fellowships to B.V., and Dr. Michel Simard for his valuable
assistance with crystallography.
́
́
de Montrea
́
l, Centre in
A.; Poveda, M. L.; Carmona, E. Organometallics 1992, 11, 2644.
(14) (a) Pandarus, V.; Zargarian, D. Chem. Commun. 2007, 978.
(b) Pandarus, V.; Zargarian, D. Organometallics 2007, 26, 4321.
(c) Salah, A. B.; Zargarian, D. Dalton Trans. 2011, 40, 8977. (d) Salah,
A. B.; Offenstein, C.; Zargarian, D. Organometallics 2011, 30, 5352.
(e) Lefev
2011, 696, 864. (f) Lefev
D. J. Mol. Catal. A 2011, 335, 1. (g) Vabre, B.; Lindeperg, F.;
Zargarian, D. Green Chem. 2013, 15, 3188. (h) Hao, J.; Mougang-
̀
re, X.; Spasyuk, D. M.; Zargarian, D. J. Organomet. Chem.
re, X.; Durieux, G.; Lesturgez, S.; Zargarian,
REFERENCES
■
̀
(1) For recent reviews on the subject of C−H functionalization see:
(a) Kakiuchi, F.; Kochi, T. Synthesis 2008, 2008, 3013. (b) Ackermann,
L. Chem. Rev. 2011, 111, 1315. (c) Yamaguchi, J.; Yamaguchi, A. D.;
Itami, K. Angew. Chem., Int. Ed. 2012, 51, 8960. (d) Ackermann, L.
Chem. Commun. 2010, 46, 4866. (e) Chen, D. Y.-K.; Youn, S. W.
Chem. Eur. J. 2012, 18, 9452.
(2) For a recent review of Ru-based C−H functionalizations see:
Arockiam, P. B.; Bruneau, C.; Dixneuf, P. H. Chem. Rev. 2012, 112,
5879.
(3) For recent reviews of Rh- and Ir- based C−H functionalization
methods see: (a) Klei, S. R.; Tan, K. L.; Golden, J. T.; Yung, C. M.;
Thalji, R. K.; Ahrendt, K. A.; Ellman, J. A.; Tilley, T. D.; Bergman, R.
G. C−H Bond Activation by Iridium and Rhodium Complexes:
Catalytic Hydrogen−Deuterium Exchange and C−C Bond-Forming
Reactions. In Activation and Functionalization of C-H Bonds; Goldberg,
K. I., Goldman, A. S., Eds.; American Chemical Society: Washington,
DC, 2004; ACS Symposium Series 885, pp 46−55. (b) Colby, D. A.;
Bergman, R. G.; Ellman, J. A. Chem. Rev. 2010, 110, 624. (c) Rouquet,
G.; Chatani, N. Angew. Chem., Int. Ed. 2013, 52, 11726.
(4) For recent reviews of Pd-based C-H functionalizations see:
(a) Lyons, T. W.; Sanford, M. S. Chem. Rev. 2010, 110, 1147. (b) Xu,
L.-M.; Li, B.-J.; Yang, Z.; Shi, Z.-J. Chem. Soc. Rev. 2010, 39, 712.
(c) Sehnal, P.; Taylor, R. J. K.; Fairlamb, I. J. S. Chem. Rev. 2010, 110,
824.
Soume,
́
B.; Vabre, B.; Zargarian, D. Angew. Chem., Int. Ed. 2014, 53,
B.; Zargarian, D.
3218−3222. (i) Hao, J.; Vabre, B.; Mougang-Soume,
Chem. Eur. J. 2014, 20, 12544. (j) Vabre, B.; Petiot, P.; Declercque, R.;
Zargarian, D. Organometallics 2014, 33, 5173.
́
(15) Gulevich, A. V.; Melkonyan, F. S.; Sarkar, D.; Gevorgyan, V. J.
Am. Chem. Soc. 2012, 134, 5528.
(16) Reaction of ethylene with Ru−phosphinite complexes obtained
from C−H ortho metalation provided one of the earliest examples of
ortho alkylation of phenol via ethylene insertion: Lewis, L. N.; Smith,
J. F. J. Am. Chem. Soc. 1986, 108, 2728.
(17) Bedford, R. B.; Coles, S. J.; Hursthouse, M. B.; Limmert, M. E.
Angew. Chem., Int. Ed. 2003, 42, 112.
́
(18) Bedford, R. B.; Hazelwood (nee Welch), S. L.; Horton, P. N.;
Hursthouse, M. B. Dalton Trans. 2003, 4164.
(19) Vabre, B.; Spasyuk, D. M.; Zargarian, D. Organometallics 2012,
31, 8561−8570.
(20) Zargarian, D.; Castonguay, A.; Spasyuk, D. M.; van Koten, G.;
Milstein, D. ECE-Type Pincer Complexes of Nickel. Top. Organomet.
Chem. 2013, 40, 131−174.
́
(21) Jimenez-Tenorio, M.; Puerta, M. C.; Salcedo, I.; Valerga, P.;
Costa, S. I.; Silva, L. C.; Gomes, P. T. Organometallics 2004, 23, 3139.
6631
dx.doi.org/10.1021/om500938u | Organometallics 2014, 33, 6623−6632

Organometallics
Article
(22) (a) Li, J.; Lutz, M.; Spek, A. L.; van Klink, G. P. M.; van Koten,
G.; Klein Gebbink, R. J. M. J. Organomet. Chem. 2010, 695, 2618.
(b) Bedford, R. B.; Hazelwood (nee Welch), S. L.; Limmert, M. E.;
́
Albisson, D. A.; Draper, S. M.; Scully, P. N.; Coles, S. J.; Hursthouse,
M. B. Chem. Eur. J. 2003, 9, 3216.
(23) (a) Dinger, M. B.; Scott, M. J. Inorg. Chem. 2001, 40, 856.
(b) Cobley, C. J.; Ellis, D. D.; Orpen, A. G.; Pringle, P. G. J. Chem. Soc.,
Dalton Trans. 2000, 1101. (c) Ng, J. K.-P.; Chen, S.; Tan, G.-K.;
Leung, P.-H. Eur. J. Inorg. Chem. 2007, 2007, 3124−3134.
(24) Boutadla, Y.; Davies, D. L.; Macgregor, S. A.; Poblador-
Bahamonde, A. I. Dalton Trans. 2009, 5820.
(25) Care was taken to ensure that all samples were treated in the
same manner. The AB doublets emerging over time in the 31P{1H}
NMR spectra and attributed to the cyclometalated complexes 3b−d
were used to estimate the extent of cyclometalation. This was done on
the basis of integration against the signal for the internal standard PPh3
contained in a carefully prepared sealed capillary that was used for all
samples.
(26) Vabre, B.; Lambert, M. L.; Petit, A.; Ess, D. H.; Zargarian, D.
Organometallics 2012, 31, 6041.
(27) Kalyani, D.; Sanford, M. S. Org. Lett. 2005, 7, 4149.
(28) Edwards, A. J.; Macgregor, S. A.; Rae, A. D.; Wenger, E.; Willis,
A. C. Organometallics 2001, 20, 2864.
(29) Nagashima, H.; Tanabiki, M. Patent Application, EP 1241175
A2, 2002.
(30) For a very recent example of Ni-based methodology for
functionalizing C−H bonds with aliphatic electrophiles, see: Song, W.;
Lackner, S.; Ackermann, L. Angew. Chem., Int. Ed. 2014, 53, 2477−
2480.
(31) SAINT, Integration Software for Single Crystal Data, Release 6.06;
Bruker AXS Inc., Madison, WI, 1999.
(32) Sheldrick, G. M. SADABS, Bruker Area Detector Absorption
Corrections; Bruker AXS Inc., Madison, WI, 1999.
(33) XPREP, X-ray Data Preparation and Reciprocal Space Exploration
Program, Release 5.10; Bruker AXS Inc., Madison, WI, 1997.
(34) SHELXTL; The Complete Software Package for Single Crystal
Structure Determination, Release 5.10; Bruker AXS Inc., Madison, WI,
1997.
(35) (a) Sheldrick, G. M. SHELXS97, Program for the Solution of
Crystal Structures; University of Gottingen, Gottingen, Germany, 1997.
(b) Sheldrick, G. M. SHELXL97, Program for the Refinement of Crystal
Structures; University of Gottingen, Gottingen, Germany, 1997.
6632
dx.doi.org/10.1021/om500938u | Organometallics 2014, 33, 6623−6632