Bench-Stable Nickel Precatalysts with Heck-type Activation

Article abstract of DOI:10.1021/acs.organomet.8b00351

Herein, we report the synthesis and characterization of a new class of air- and moisture-stable phosphine-containing nickel(II) precatalysts, which activate through a Heck-type mechanism. The activities of the precatalysts are demonstrated with a carbonyl

Full text of DOI:10.1021/acs.organomet.8b00351

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Cite This: Organometallics XXXX, XXX, XXX−XXX
Bench-Stable Nickel Precatalysts with Heck-type Activation
Jessica M. Weber, Ashley R. Longstreet, and Timothy F. Jamison*
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States
S
* Supporting Information
ABSTRACT: Herein, we report the synthesis and character-
ization of a new class of air- and moisture-stable phosphine-
containing nickel(II) precatalysts, which activate through a
Heck-type mechanism. The activities of the precatalysts are
demonstrated with a carbonyl−ene coupling reaction.
INTRODUCTION
■
Nickel catalysis is important for providing access to structural
motifs found in natural products and therapeutics.1 Nickel
offers unique properties relative to other more expensive
transition metals, such as the accessibility of multiple oxidation
states,2 and may demonstrate reactivity complementary to that
of palladium in a variety of coupling reactions.3
Despite the utility of nickel as a catalyst, the limited number
of sources of this transition metal in its lower oxidation states,
such as Ni(0), has inhibited the development and broader
adoption of new synthetic methods. Many Ni(0) complexes,
such as Ni(COD)2 (COD = 1,5-cyclooctadiene), are unstable
in the presence of even moderate amounts of oxygen, light,
heat, and water, thereby necessitating Schlenk line techniques
and/or glovebox usage.4 In comparison, Ni(II) species, such as
NiCl2, tend to display greater stability under common ambient
conditions and often are comparatively less expensive.
However, reduction to an active catalyst, for example a
Ni(0) species, often requires reagents or conditions to which
Figure 1. (a) Examples of Ni(II) precatalysts. (b) Proposed activation
mechanism of Ni-1. (c) Proposed Heck-type activation of the new
many common functional groups would not be compatible.5
In order to address these challenges and limitations,6
class of Ni(II) precatalysts.
multiple research groups4,5,7−12 have sought to develop air-
and water-stable Ni(II) complexes that have both the desired
Ni(COD)2. As shown in Figure 1c, the Ni(II) precatalysts
stability of Ni(II) and provide an active catalyst in situ under
were designed to include an aryl ligand with an appended
mild conditions (Figure 1a). Many such “precatalysts” are
alkene chain. Activation with a triflate source, we reason,
effective for a number of transformations, including C−C and
creates a cationic nickel species that undergoes alkene
C−N bond-forming reactions. Common modes of activation
coordination, migratory insertion, and β-hydride elimination
to Ni(0) include the use of high temperatures and Grignard
to afford the desired Ni(0) species. Thus, unlike Ni-1 or the
reagents. An exception is (PPh3)2Ni(o-tolyl)Cl (Ni-1),4 which
precatalysts described by other groups, activation would occur
we demonstrated can be activated at room temperature with a
under relatively mild conditions and avoid wasting 50% of the
silyl triflate to yield a proposed cationic nickel species (Figure
nickel precatalyst.
1b). Transmetalation between two nickel complexes followed
by reductive elimination of a nickel biaryl species then provides
the active Ni(0). Although this process occurs under relatively
RESULTS AND DISCUSSION
As shown in Figure 2, seven Ni-complexes, each stable for a
period of at least 6 months in their solid state, were synthesized
by transmetalation (Method A) or oxidative addition (Method
■
mild conditions, only a maximum of 50% of the Ni-1
precatalyst is transformed into active Ni(0) species.4
Recently, we reported N-heterocyclic carbene (NHC)-
B) methods. The precatalysts were designed to bear unique
containing precatalysts that activate through an intramolecular
Heck-type reaction.13 Building on this work, herein we
describe a new class of bench-stable, phosphine-containing
precatalysts that can be synthesized without the use of
Received: May 29, 2018
© XXXX American Chemical Society
A
DOI: 10.1021/acs.organomet.8b00351
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disordered in the X-ray crystal structure of Ni-2, the 1H
NMR spectrum revealed alkene isomerization and a 0.6:1
mixture of cis to trans olefins regardless of the synthetic
method. Alkene somerization to the cis olefin was also
1
observed in the H NMR spectra of Ni-3a, Ni-3b, and Ni-4
and further confirmed by X-ray crystallography in the case of
the first two.
With the Ni-2−Ni-6 precatalysts in hand, we initially
explored their catalytic activity in a carbonyl−ene reaction
between benzaldehyde (7) and 1-octene (8) at room
temperature (Table 2). Precatalyst activation at 20 mol %
loadings was achieved using TESOTf (1.75 equiv) and Et3N (6
equiv). As shown in Table 2, entry 3, the use of Ni-2 resulted
in the formation of the desired linear product 9 in 93 and 95%
yield after 24 and 48 h, respectively. Gratifyingly, Ni-2 not only
was successfully activated under these conditions but also
displayed catalytic activity comparable to that of the widely
used Ni(COD)2/PPh3 (Table 2, entry 1). Interestingly, when
1 equiv of COD was added to the reaction with Ni-2, the yield
of 9 dropped to 86% in 48 h (data not shown). In contrast, Ni-
3a (Table 2, entry 4), which is sparingly soluble in toluene,
yielded only trace product after 48 h. The use of precatalysts
Ni-3b (Table 2, entry 5), Ni-4 (Table 2, entry 6), or Ni-5a
(Table 2, entry 7) also resulted in poor to moderate yields of 9.
Precatalyst Ni-5b featuring the PCy2Ph ligand15 provided a
mixture of the linear (9) and branched (10) products in 13
and 47% yield, respectively. This is noteworthy given the
comparable performance of Ni(COD)2/PCy2Ph (Table 2,
entry 9), which undergoes a more conventional activation
pathway to generate the same active catalyst. Finally, Ni-6,
which differs from Ni-2 by the presence of a trisubstituted
alkene, also provided 9 in a favorable yield of 84%, albeit
requiring a more prolonged 48 h reaction time.
Having observed promising reactivity between aldehyde 7
and alkene 8 in the presence of 20 mol % Ni-2 and Ni-6, the
same carbonyl−ene transformation was repeated at reduced
precatalyst loadings of 5 mol % for a reaction time of 24 h. As
shown in Table 3, the yield of product 9 yield was highest for
Ni-2 (entry 4). This improved yield with Ni-2 relative to
Ni(COD)2/PPh3 is consistently observed with multiple
substrates (Table 4). Decreasing the catalyst loading of Ni-6,
which was shown above to perform more sluggishly than Ni-2,
greatly reduced the product yield (ca. 37%) (Table 3, entry 5).
However, heating the reaction to 60 °C aided in improving the
yield of 9 to 77% (Table 3, entry 5).17
We next set out to substantiate our proposed Heck-type
mechanism as the mode of precatalyst activation. We
additionally wanted to explore the potential for thermal
activation, as heating improved the yield of 9 with Ni-6.
Indeed, Heck activation product 11 was observed by HRMS
and GC/MS following activation of precatalyst Ni-6 via a
triflate source as well as under thermal conditions (60 °C) in
the absence of triflate (Scheme 1).18,19 The ability of this
complex to activate under multiple conditions bodes well for
greater substrate functional group compatibility. Precatalyst
activation under thermal conditions may broaden the scope of
reactions to which these precatalysts can be applied.
Figure 2. Synthesis of Ni(II) precatalysts. Compounds with suffix “a”
were treated with a saturated solution of LiCl in THF and those with
suffix “b” were treated with solution of LiCl (5 equiv) in a mixture of
MeOH/toluene (8:1).
combinations of aromatic, appended alkene, and phosphine
ligands. In Method A, the corresponding Grignard reagent
prepared from aryl halide 2−6 was added dropwise to
4
(PR3)2NiCl2 or (PR3)2NiBr2 in THF to generate Ni-2−Ni-
6 respectively.14 Notably, when using Grignard and Ni(II)
substrates with mitsmatched halide ligands, a mixture of
bromo- and chloro-precatalyst was obtained. This was easily
remedied by treating the mixture with a solution of excess LiCl
to isolate the pure chloride-containing precatalyst. In synthesis
Method B, the corresponding aryl substrate was treated with
Ni(COD)2 and PPh3 in THF. While this method provided a
moderate improvement in the yield of Ni-6, it led to
degradation in the case of substrates Ni-3a and Ni-3b and
lower yields of Ni-2.
Crystals suitable for X-ray crystallography were obtained for
Ni-2, Ni-3a, Ni-3b, Ni-5a, and Ni-6. Each precatalyst was
revealed to have a square planar geometry for each with trans
phosphine ligands, which is consistent with the singlet
observed in the 31P NMR spectra (Table 1). Ni−P bond
lengths ranged from 2.198 to 2.219 Å, which are comparable to
similar complexes.16 While the aliphatic side chain was
CONCLUSIONS
■
Seven precatalysts featuring alkene-functionalized aryl ligands
were synthesized and characterized. These bench-stable
complexes activate via an intramolecular Heck-type mechanism
under relatively mild conditions, specifically TESOTf or mild
B
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a
Table 1. Bond Length, Angles, and ORTEP Crystal Structures of Ni-2, Ni-3a, Ni-3b, Ni-5a, and Ni-6 Precatalysts
precatalyst
bond
bond length (Å)
angle
angle (deg)
Cl1−Ni
P1−Ni
P2−Ni
C1−Ni
Cl1−Ni
P1−Ni
P2−Ni
C1−Ni
Cl1−Ni
P1−Ni
P2−Ni
C1−Ni
Cl1−Ni
P1−Ni
P2−Ni
C1−Ni
Cl1−Ni
P1−Ni
P2−Ni
C1−Ni
2.236(1)
2.212(1)
2.216(1)
1.898(3)
2.231(1)
2.2188(9)
2.2123(9)
1.890(4)
2.2222(5)
2.1985(5)
2.2100(5)
1.892(1)
2.216(1)
2.2072(8)
2.2164(8)
1.895(2)
2.241(1)
2.214(1)
2.214(1)
1.899(3)
Cl1−Ni−P1
P1−Ni−C1
C1−Ni−P2
P2−Ni−Cl1
Cl1−Ni−P1
P1−Ni−C1
C1−Ni−P2
P2−Ni−Cl1
Cl1−Ni−P1
P1−Ni−C1
C1−Ni−P2
P2−Ni−Cl1
Cl1−Ni−P1
P1−Ni−C1
C1−Ni−P2
P2−Ni−Cl1
Cl1−Ni−P1
P1−Ni−C1
C1−Ni−P2
P2−Ni−Cl1
89.14(4)
91.0(1)
87.1(1)
93.81(4)
90.78(4)
89.8(1)
Ni-2
Ni-3a
Ni-3b
Ni-5a
Ni-6
89.3(1)
90.06(4)
90.71(2)
88.26(4)
90.31(4)
90.96(2)
92.50(3)
87.97(6)
88.78(6)
90.78(3)
89.14(4)
91.0(1)
87.1(1)
93.81(4)
a
ORTEP structures shown at 50% probability and hydrogen atoms are excluded for clarity. Disorder of the alkyl chains of Ni-2, Ni-5a, and Ni-6 are
not shown.
Table 2. Investigation of Precatalyst Activity in a Carbonyl−
Ene Coupling Reaction
Table 3. Comparison of Ni-2 and Ni-6 Activity with Ni-1
and Ni(COD)2/PPh3 in a Carbonyl−Ene Coupling Reaction
a
% yield of 9
a
entry
precatalyst
precatalyst loading (mol %) % yield of 9
entry
precatalyst
24 h
48 h
82
87
95
1
44
16
15
b
1
2
3
4
5
Ni-1
10
5
5
5
5
72
70
59
83
1
2
3
4
5
6
7
8
9
10
Ni(COD)2, 2 PPh3
81
85
93
b
b
Ni-1
Ni-1
Ni(COD)2, PPh3
Ni-2
Ni-6
Ni-2
Ni-3a
c
37 (77)
Ni-3b
a
Yields determined by GC relative to dodecane as an internal
standard after 24 h. Due to mode of activation, Ni-1 maximum active
catalyst is half of catalyst loading. Reaction heated to 60 °C.
Ni-4
Ni-5a
b
c
c
c
Ni-5b
Ni(COD)2, 2 PCy2Ph
13 (47)
19 (54)
84
Ni-6
53
multiple activation conditions, we are exploring other
applications of these precatalysts, especially in reactions that
do not require the use of a triflate source or transmetallating
reagent.
a
Yields determined by GC relative to dodecane as an internal
standard. Precatalyst loading was 20 mol %; maximum active catalyst
is 10 mol %. Yield of 10.
b
c
EXPERIMENTAL SECTION
Materials, Methods, and General Considerations. Reactions
were carried out under N2 using standard glovebox and Schlenk
heating. Among the precatalysts developed, Ni-2 was found to
outperform Ni(COD)2/PPh3 and Ni-1 in a carbonyl−ene
reaction at different precatalyst loadings. With the potential for
■
C
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Table 4. Comparison of Ni-2 Activity with Ni(COD)2/PPh3 at 5 and 20 mol % Catalyst Loadings in a Carbonyl−Ene Reaction
with Electron- and Electron-Rich Aldehyde Coupling Partners
a
1
Yields determined by H NMR with MeNO2 added after quenching as an internal standard for NMR quantification. Reactions ran in duplicate,
yields are 2%.
performed by Atlantic Microlabs, Inc., on the complexes that did
not successfully crystallize.
Scheme 1. Evidence for Heck-type Activation of Ni-6 Both
Thermally and via Addition of TESOTf
General Procedures for Synthesis of Nickel Complexes.
Bromide Grignard Synthesis. In a glovebox, solid magnesium (1.1
equiv) was added to a solution of arene (1 equiv) in THF (0.5 M) in
a 2 dram vial. The vial was sealed tightly and removed from the box.
This reaction was stirred for 24 h at room temperature and used
without any purification. Additionally, a color change from clear to
brown was observed during these reactions.
Chloride Grignard Synthesis. In a glovebox, solid magnesium (1.1
equiv) was added to a solution of arene (1 equiv), iodine (0.01 equiv)
in THF (0.5 M) in a Schlenk flask. The flask was then sealed,
removed form the glovebox, and heated to 60 °C. The reaction was
stirred for 24 h and then cooled to room temperature. The Grignard
was used without further purification.
techniques at ambient temperature (23−27 °C) under Ar unless
otherwise noted. Diethyl ether (Et2O), tetrahydrofuran (THF),
dimethylformamide (DMF), and dichloromethane (DCM) were
degassed by sparging with nitrogen and dried via passage through a
column of activated alumina on a Glass Contour solvent purification
system. Methanol (>99.8%) and pentane were used as received.
Complexes (PPh3)2NiBr2, (PPh3)2NiCl2, and (PPh3)2Ni(o-tolyl)Cl
were prepared according to previously published procedures.4,16
Authentic samples of compounds 9 and 10 were synthesized via
Transmetalation Method (Method A). Under Ar gas, nickel
complex (PR3)2NiX2 was dissolved in THF (0.15 M) in an oven-dried
round-bottomed flask containing a magnetic stir bar. The solution was
cooled to 0 °C with an ice bath, and then the Grignard reagent (1
equiv) was added dropwise via syringe. The solution was stirred for 5
min, after which the reaction was quenched with 2 mL of MeOH. The
solution was then evaporated to dryness under reduced pressure to a
sticky tar. MeOH (5 mL) was added and the mixture was sonicated
until a yellow solid precipitated (ca. 2 min). The precipitate was
collected by vacuum filtration, washed (with MeOH, 2 × 25 mL, and
pentane, 1 × 10 mL) and dried under high vacuum to yield the
complex. The complexes were then purified via recrystallization from
DCM/MeOH with a stream of Ar gas used to evaporate the DCM.
Oxidative Addition Method (Method B). In a glovebox, Ni-
(COD)2 (1 equiv) and PPh3 (2 equiv) were dissolved in THF (0.4
M). The desired arene (1.1 equiv) was added and the vial was sealed,
removed from the glovebox, and stirred for 18 h at room temperature.
The solution was then opened to air and filtered through a plug of
Celite. The solution was evaporated to dryness under reduced
pressure to a sticky tar. MeOH (5 mL) was added, and the mixture
was sonicated until a yellow solid precipitated (∼2 min). The
precipitate was collected by vacuum filtration, rinsed with MeOH (2
× 25 mL), and pentane (10 mL), and dried under high vacuum to
yield the complex. The complexes were purified via recrystallization
from DCM/MeOH with evaporation under a steam of argon.
previously published methods.16 Purity was determined by 31P, H,
1
and 13C NMR. NMR chemical shifts are reported in ppm relative to
TMS (13C, 1H) and 85% H3PO4 (31P, as an external standard). Unless
otherwise noted, NMR spectra were collected at room temperature
(23−27 °C). Gas chromatography (GC) analyses were performed on
an Agilent 7890A GC system with an autosampler and (5%-phenyl)-
methylpolysiloxane column coupled to a flame ionization detector.
Gas chromatography/mass spectroscopy (GC/MS) analyses were
performed on an Agilent 5975C with a triple-axis detector using an
autosampler and (5%-phenyl)-methylpolysiloxane column coupled to
a quadrupole MSD. Dodecane (1 equiv) was used as an internal
standard for determination of yields relative calibration curves to
determine yield. Melting points were collected on eletrothermal
apparatus using glass capillaries. Infrared spectroscopy (IR) spectra
were collected using an Agilent Cary 630 FT-IR spectrometer
equipped with an ATR accessory. Peaks from the fingerprint region
were omitted from the report for clarity. High-resolution mass
spectroscopy (HRMS) was obtained on a Bruker Daltonics APEXIV
4.7 T FT-ICR-MS outfitted with either an electrospray ionization
(ESI) or an IonSense DART ion source. X-ray diffraction was
performed on a Bruker APEX. Elemental analyses (EA) were
D
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Synthesis and Characterization of Complexes. Ni-2. The
Grignard of 2 (6 mL, 3 mmol, 0.5 M) was prepared via reaction of
500 mg of 2 and 80 mg of powdered magnesium in 6 mL of THF,
using the general procedure for preparation of chloride Grignard.
Then, Ni-2 was prepared via dropwise addition of 6 mL of this
Grignard solution to 1.96 g of (PPh3)2NiCl2 in 20 mL of THF
following the general transmetalation procedure (Method A). Yield:
790 mg (35%). Alternatively, Ni-2 was prepared via the general
oxidative addition method (Method B) by addition of 1.47 g of 2 to
2.20 g of Ni(COD)2 and 4.20 g of PPh3 in 20 mL of THF. Yield: 1.68
mg (28%). Crystals suitable for single-crystal X-ray diffraction were
grown by the slow diffusion of methanol into a saturated solution of
Ni-2 in dichloromethane at −30 °C. 1H NMR (400 MHz, C7D9, 223
K, δ): 7.72 (brs, 12H), 7.47 (d, J = 7.7 Hz, 1H), 7.39 (d, J = 7.7 Hz,
1H), 7.29−7.36 (m, 1H), 7.15 (s, 6H), 6.63 (t, J = 8.0 Hz, 2H),
6.24−6.38 (m, 3H), 5.55 (q, J = 8.0 Hz, 1H), 5.27 (m, 1H), 4.59 (m,
2H), 3.83 (d, J = 9.0 Hz, 1H), 3.77 (d, J = 9.0 Hz, 1H), 1.59 (d, J =
6.7 Hz, 1H), 1.36 (d, J = 6.7 Hz, 3H) ppm. 13C{1H} NMR (101
MHz, CD2Cl2, 258 K, δ): 134.8 (t, 3JCP = 6.0 Hz), 131.6, 131.5, 130.0,
133.3 (dt, 3JCP = 5.5 Hz), 131.4, 130.9, 130.0, 129.8, 128.2 (dt, 3JCP
=
4.8 Hz), 124.9, 124.7, 123.8, 115.0 (dt, 3JCP = 6.5 Hz), 104.6, 12.8 (t,
1JCP = 17.2 Hz), 10.3 ppm. 31P NMR (121 MHz, C6D6, δ): 7.2 ppm.
HRMS-ESI (m/z): Predicted: [C39H37NiOP2]+: 641.1668 m/z.
Found: [C39H37NiOP2]+: 641.1680 m/z. IR alkene stretch (ATR,
cm−1): 3054.4. Melting Point: 150 °C.
Ni-4. The Grignard of 4 (8 mL, 4 mmol, 0.5 M) was prepared via
reaction of 1.08 g of 4 and 53 mg of powdered magnesium in 8 mL of
THF, using the general procedure for preparation of bromide
Grignard. Then, Ni-4 was prepared via dropwise addition of 8 mL of
this Grignard solution to 1.77 g of (PPh3)2NiCl2 in 30 mL of THF
following the general transmetalation procedure (Method A). Yield:
1.75 g (52%). 1H NMR (400 MHz, C6D6, δ): 7.88 (s, 11H), 7.50 (s,
1H), 7.33−7.45 (m, 1H), 7.01 (s, 18H), 6.40 (d, J = 8.4 Hz, 1H),
5.71 (d, J = 8.4 Hz, 1H), 5.41 (d, J = 7.0 Hz, 1H), 4.61 (t, J = 7.0 Hz,
2H), 2.01 (d, J = 7.0 Hz, 3H), 1.21 (s, 1H), 1.05 (s, 8H) ppm. 13C
3
NMR (101 MHz, CCl2D2, δ): 143.9, 142.6, 135.2 (t, JCP = 5.5 Hz),
133.6, 132.9 (t, 2JCP = 21.8 Hz), 130.0, 128.0 (t, 3JCP = 4.8 Hz), 120.6,
113.2, 103.6, 34.0, 31.6, 10.2 ppm. 31P NMR (121 MHz, C6D6, δ):
22.8 ppm. Anal. Calcd for C49H47BrNiOP2: C, 69.04; H, 5.56. Found:
C, 68.77; H, 5.70. HRMS-ESI (m/z): Predicted: [C49H47NiOP2]+:
771.2459 m/z. Found: [C49H47NiOP2]+: 771.2471 m/z. IR alkene
stretch (ATR, cm−1): 3052.9. Melting point: 167−168 °C.
3
128.1 (t, JCP = 5.4 Hz), 110.0, 37.4, 12.8, 1.5, 0.1 ppm. 31P NMR
(121 MHz, C6D6, δ): 21.1 ppm. IR (powder ATR, cm−1): 3050.9.
HRMS-ESI (m/z): Predicted: [C46H41NiP2]+: 729.1981 m/z. Found:
[C46H41NiP2]+: 729.1968 m/z. Anal. Calcd for C46H41ClNiP2: C,
73.67; H, 5.51. Found: C, 73.49; H, 5.39.20 Melting Point: 132−133
°C.
Ni-5a. The Grignard of 5 (3 mL, 1.5 mmol, 0.5 M) was prepared
via reaction of 437 mg of 5 and 40 mg of powdered magnesium in 3
mL of THF, using the general procedure for preparation of bromide
Grignard. Then, Ni-5a was prepared via dropwise addition of 3 mL of
this Grignard solution to 981 mg of (PPh3)2NiCl2 in 10 mL of THF
following the general transmetalation procedure (Method A). Yield:
735 mg (59%). The general procedure was followed except the
precatalyst underwent halogen exchange reaction via stirring in
MeOH and toluene (8:1, 0.1 M) with 5 equiv of LiCl for 18 h. To
isolate, the reaction was concentrated and sonicated in MeOH to give
a yellow solid, which was washed 3 × 25 mL with MeOH. This was
done in order to remove any of the bromide-containing complex.
Crystals suitable for single-crystal X-ray diffraction were grown by the
slow diffusion of pentane into a toluene solution of Ni-5a at −30 °C.
1H NMR (400 MHz, C6D6, δ): 10.13 (d, J = 7.6 Hz, 1H), 7.81 (s,
12H), 7.38 (s, 2H) 7.27 (s, 1H), 7.03 (s, 4H), 6.95 (s, 15H), 5.88−
5.61 (m, 1H), 5.72 (d, J = 9.8 Hz, 1H), 5.10−5.28 (m, 2H), 3.18 (s,
Ni-3a. The Grignard of 3 (12 mL, 6 mmol, 0.5 M) was prepared
via reaction of 1.58 g of 3 and 160 mg of powdered magnesium in 12
mL of THF, using the general procedure for preparation of bromide
Grignard. Then, Ni-3a was prepared via dropwise addition of 12 mL
of this Grignard solution to 3.92 g of (PPh3)2NiCl2 in 40 mL of THF
following the general transmetalation procedure (Method A). Yield:
1.51 g (32%). The general procedure was followed except the
precatalyst underwent a halogen exchange reaction via stirring in LiCl
sat. THF for 18 h. To isolate, the mixture was filtered through a plug
of Celite, concentrated, and sonicated in 5 mL MeOH to give a yellow
solid, which was washed 3 × 25 mL with MeOH. This was done in
order to remove any of the bromide-containing complex. Crystals
suitable for single-crystal X-ray diffraction were grown by the slow
diffusion of pentane into a dichloromethane solution of Ni-3a at −30
°C. 1H NMR (400 MHz, C6D6, δ): 10.17 (d, J = 7.6 Hz, 1H), 7.81 (s,
9H), 7.27−7.42 (m, 4H), 7.03 (t, J = 7.6 Hz, 3H), 6.89−6.97 (m,
17H), 6.82 (d, J = 8.2 Hz, 1H), 6.03 (d, J = 8.2 Hz, 1H), 5.44 (d, J =
6.1 Hz, 1H), 4.65 (quintet, J = 6.1 Hz, 1H), 1.96 (d, J = 7.6 Hz, 3H)
ppm. 13C NMR (101 MHz, CCl2D2, δ): 157.5, 143.3, 141.3, 135.0 (t,
2H), 2.23 (brs, 2H), 2.05 (brs, 2H) ppm. 13C NMR (101 MHz,
2
CCl2D2, 258 K, δ): 157.5, 140.1, 138.7, 134.7, 134.5, 132.0 (t, JCP
=
3
20.4 Hz), 130.3, 130.1, 127.9, 127.6 (t, JCP = 5.1 Hz), 124.1, 123.4,
121.8, 114.9, 110.8, 66.8, 30.6, 28.9, 0.5 ppm. 31P NMR (121 MHz,
C6D6, δ): 21.3 ppm. HRMS-ESI (m/z): Predicted: [C51H45NiOP2]+:
793.2294 m/z. Found: [C51H45NiOP2]+: 793.2282 m/z. IR alkene
stretch (ATR, cm−1): 3049.9. Melting point: 132 °C.
1
3JCP = 5.4 Hz), 134.3, 134.1, 132.3 (t, JCP = 22.4 Hz), 131.4, 130.9,
3
130.1, 129.3, 129.0, 127.9 (t, JCP = 5.0 Hz), 124.8, 124.4, 124.3,
115.4, 104.6, 10.3 ppm. 31P NMR (121 MHz, C6D6, δ): 21.6 ppm.
HRMS-ESI (m/z): Predicted: [C49H41NiP2]+: 765.1981 m/z. Found:
[C49H41NiP2]+: 765.1984 m/z. IR alkene stretch (ATR, cm−1):
3049.7. Melting point: 183−184 °C.
Ni-5b. The Grignard of 5 (20 mL, 10 mmol, 0.5 M) was prepared
via reaction of 2.91 g of 5 and 266 mg of powdered magnesium in 20
mL of THF, using the general procedure for preparation of bromide
Grignard. Then, Ni-5b was prepared via dropwise addition of 20 mL
of this Grignard solution to 6.78 g of (PCy2Ph)2NiCl2 in 60 mL of
THF following the general transmetalation procedure (Method A).
Yield: 5.81 g (68%). The general procedure was followed except the
precatalyst underwent halogen exchange reaction via stirring in
MeOH and toluene (8:1, 0.1 M) with 5 equiv of LiCl for 18 h. To
isolate, the reaction was concentrated and sonicated in MeOH to give
a yellow solid, which was washed 3 × 25 mL with MeOH. This was
done in order to remove any of the bromide-containing complex.
Crystals suitable for single-crystal X-ray diffraction were grown by the
slow diffusion of pentane into a toluene solution of Ni-5b at −30 °C.
1H NMR (400 MHz, C6D6, δ): 10.62 (s, 1H), 6.76−8.22 (m, 18H),
6.36 (s, 1H), 5.91 (s, 1H), 4.99−5.35 (m, 1H), 3.73 (s, 1H), 0.66−
2.67 (m, 46H) ppm. 13C NMR (101 MHz, CCl2D2, 258 K, δ): 159.7,
142.0, 138.5, 133.0, 131.1, 129.0, 128.3, 127.6, 127.2, 124.0, 123.3,
122.2, 115.1, 111.1, 34.0, 33.5, 30.6, 30.0, 29.7, 29.2, 28.8, 27.7, 26.6
ppm. 31P NMR (121 MHz, C6D6, δ): 16.2 ppm. Anal. Calcd for
C51H69ClNiOP2: C, 71.71; H, 8.14. Found: C, 71.43; H, 8.30. HRMS-
ESI (m/z): Predicted: [C51H69NiOP2]+: 817.4172 m/z. Found:
Ni-3b. The Grignard of 3 (3 mL, 1.5 mmol, 0.5 M) was prepared
via reaction of 395 mg of 3 and 40 mg of powdered magnesium in 3
mL of THF, using the general procedure for preparation of bromide
Grignard. Then, Ni-3b was prepared via dropwise addition of 3 mL of
this Grignard solution to 795 mg of (PPh2Me)2NiCl2 in 10 mL of
THF following the general transmetalation procedure (Method A).
Yield: 280 mg (28%). The general procedure was followed except the
precatalyst underwent a halogen exchange via stirring with LiCl
saturated THF for 18 h. To isolate, the mixture was filtered through a
plug of Celite, concentrated, and sonicated in MeOH to give a yellow
solid, which was washed 3 × 25 mL with MeOH. This was done in
order to remove any of the bromide-containing complex. Crystals
suitable for single-crystal X-ray diffraction were grown by the slow
1
diffusion of pentane into a toluene solution of Ni-3b at −30 °C. H
NMR (400 MHz, C6D6, δ): 9.49 (d, J = 8.4 Hz, 1H), 7.71−7.77 (m,
4H), 7.63 (q, J = 7.4 Hz, 4H), 7.45 (d, J = 8.4 Hz, 1H), 7.30 (t, J = 7.4
Hz, 1H), 6.96−7.05 (m, 8H), 6.88−6.94 (m, 5H), 6.51 (d, J = 8.4 Hz,
1H), 6.18 (dd, J = 7.4 Hz, 1H), 4.64 (quintet, J = 7.4 Hz, 1H), 1.95
(dd, J = 7.6 Hz, 3H), 1.24 (t, J = 3.7 Hz, 6H) ppm. 13C NMR (101
1
MHz, CCl2D2, δ): 157.2, 143.1, 141.3, 134.4 (dt, JCP = 21.0 Hz),
E
DOI: 10.1021/acs.organomet.8b00351
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
[C51H69NiOP2]+: 817.4155 m/z. IR alkene stretch (ATR, cm−1):
3043.0. Melting point: 138 °C.
Timothy F. Jamison: 0000-0002-8601-7799
Present Address
Ni-6. The Grignard of 6 (2 mL, 1 mmol, 0.5 M) was prepared via
reaction of 180 mg of 6 and 20 mg of powdered magnesium in 2 mL
of THF, using the general procedure for preparation of chloride
Grignard. Then, Ni-6 was prepared via dropwise addition of 2 mL of
this Grignard solution to 654 mg of (PPh3)2NiCl2 in 5 mL of THF
following the general transmetalation procedure (Method A). Yield:
305 mg (40%). Alternatively, Ni-6 was prepared via the general
oxidative addition method (Method B) by addition of 198 mg of 6 to
275 mg of Ni(COD)2 and 524 mg of PPh3 in 10 mL of THF. Yield:
410 mg (53%). Crystals suitable for single-crystal X-ray diffraction
were grown by the slow diffusion of methanol into a dichloromethane
A.R.L.: Department of Chemistry, Biochemistry, and Physics,
The University of Tampa 401 West Kennedy Boulevard,
Tampa, FL 33606, USA.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported by the Bill and Melinda Gates
Foundation (“Medicines for All” Initiative) and the NIH under
the Ruth L. Kirschstein National Research Service Award
F32GM120852 from the NIGMS (A.R.L.), and the National
Science Foundation CHE-0946721 (X-ray Crystallography).
We thank Li Li and Liam Kelly for HRMS data and Dr. Peter
1
solution of Ni-6 at −30 °C. H NMR (400 MHz, C6D6, δ): 7.74 (s,
11H), 7.37 (d, J = 7.4 Hz, 2H), 7.01 (s, 18H), 6.59 (brs, 1H), 6.28−
6.41 (m, 1H), 4.56 (s, 1H), 4.00, (d, J = 7.4 Hz, 2H), 1.62 (s, 3H),
1.47 (s, 3H) ppm. 13C NMR (101 MHz, CCl2D2, 258 K, δ): 147.2,
136.5, 135.2 (t, 3JCP = 5.8 Hz), 132.3, 132.2 (t, 1JCP = 21.5 Hz), 130.2,
3
128.3 (t, JCP = 5.0 Hz), 123.6, 123.4, 122.7, 68.3, 39.3, 25.8, 17.9
ppm. 31P NMR (121 MHz, C6D6, δ): 21.1 ppm. HRMS-ESI (m/z):
Predicted: [C47H43NiOP2]+: 727.2188 Found: [C47H43NiOP2]+:
727.2168. Anal. Calcd for 85% Ni-6·15% CH2 Cl2 :
C40.1H36.85Cl1.15Ni0.85P1.7: C, 72.74; H, 5.61. Found: C, 72.52; H,
5.53. IR alkene stretch (ATR, cm−1): 3039.9. Melting point: 154 °C.
Procedure and Characterization for the Carbonyl−Ene
Reaction. In a glovebox, the desired precatalyst (5−20 mol %) was
added to a 2 dram vial containing a solution of alkene (1 mmol, 5
equiv), triethylamine (1.2 mmol, 6 equiv), and aldehyde (0.20 mmol,
1 equiv) dissolved in toluene (2 mL). Where 1-octene and
benzaldehyde were used, dodecane (0.2 mmol, 1 equiv) was also
added as internal standard for the subsequent GC analysis. This
mixture was stirred for 30 s after which TESOTf (1.75 equiv, 0.35
mmol) was added via syringe. The vial was then tightly sealed and
stirred at room temperature for 24 or 48 h. Reactions were quenched
by exposure to air. In the case of 1-octene, yields were determined
using GC against a standard curve of product 9, with ca. 100 uL
aliquot of the crude reaction mixture being diluted to 1 mL with
dicholormethane for analysis.18 In all other cases, the yields were
determined by 1H NMR relative to a standard addition of
nitromethane. NMR samples were prepared by filtering the crude
reaction mixture through a plug of silica, which was then washed 2 mL
of dichloromethane. The filtrate was then concentrated to dryness,
dissolved in CDCl3, and 1 equiv of nitromethane added as an internal
Muller, Jonathan Becker, and Charlene Tsay (Massachusetts
̈
Institute of Technology) for the X-ray crystallography data. We
are also grateful to Dr. Justin A.M. Lummiss, Dr. Peter D.
Morse, Dr. Eric A. Standley, and Dr. Laurel M. Heckman for
helpful discussions and to Dr. Rachel L. Beingessner for
contributing to the preparation of the manuscript.
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ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.organo-
met.8b00351.
■
S
General experimental procedures, synthesis of aryl
precursors, spectral data, and X-ray crystallographic
data (PDF)
Accession Codes
CCDC 1583496−1583500 contain the supplementary crys-
tallographic data for this paper. These data can be obtained
free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by
emailing 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.
AUTHOR INFORMATION
Corresponding Author
*E-mail: tfj@mit.edu.
ORCID
■
Jessica M. Weber: 0000-0002-8434-0066
F
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(19) Ni-6 was chosen for activation tests due to the Heck product’s
inability to isomerize. Additionally, 11 was identified based on
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(20) Due to the instability of Ni-2 in solution, a full carbon spectra
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elemental analysis was obtained.
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DOI: 10.1021/acs.organomet.8b00351
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