Synthetic analogs for evaluating the influence of N-H...S hydrogen bonds on the formation of thioester in acetyl coenzyme a synthase

Article abstract of DOI:10.1039/b901192g

A series of square planar methylnickel(II) complexes, (dppe)Ni(Me)(SAr) (dppe = 1,2-bis(diphenylphosphino)ethane); 2. Ar = phenyl; 3. Ar = pentafluorophenyl; 4. Ar = o-pivaloylaminophenyl; 5. Ar = p-pivaloylaminophenyl; (depe)Ni(Me)(SAr), (depe = 1,2-bis(diethylphosphino)ethane); 7. Ar = phenyl; 8. Ar = pentafluorophenyl; 9. Ar = o-pivaloylaminophenyl; 10. Ar = p-pivaloylaminophenyl), were synthesized via the reaction of (dppe)NiMe ₂ (1) and (depe)NiMe₂ (6) with either the corresponding thiol or disulfide. These complexes were characterized by various spectroscopic methods including ³¹P NMR, ¹H NMR, ¹³C NMR and infrared spectroscopies and in most cases by X-ray diffraction analyses. Solid state and solution measurements establish that 4 and 9 contain intramolecular N-H...S bonds. Carbonylation of the complexes 2-4, 7-10 leads to (dRpe)Ni(CO)₂ and MeC(O)SAr via the intermediacy of the acylnickel adducts, (dRpe)Ni(C(O)Me)(SAr), detected at low temperature by ³¹P NMR spectroscopy. Consistent with experimental observations, density functional theory results reveal that the intramolecular hydrogen bond in 9 stabilizes the acylnickel adduct compared with its non-hydrogen-bonded adduct, 10. Oxidative addition of MeC(O)SC₆F₅ to (dRpe)Ni(COD) followed by spontaneous decarbonylation proceeds in variable yields generating 3 and 8.

Full text of DOI:10.1039/b901192g

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PAPER
www.rsc.org/dalton | Dalton Transactions
Synthetic analogs for evaluating the influence of N–H ◊ ◊ ◊ S hydrogen bonds
on the formation of thioester in acetyl coenzyme a synthase†
Piyal W. G. Ariyananda, Matthew T. Kieber-Emmons, Glenn P. A. Yap and Charles G. Riordan*
Received 26th January 2009, Accepted 8th April 2009
First published as an Advance Article on the web 27th April 2009
DOI: 10.1039/b901192g
A series of square planar methylnickel(II) complexes, (dppe)Ni(Me)(SAr) (dppe = 1,2-bis(diphenylpho-
sphino)ethane); 2. Ar = phenyl; 3. Ar = pentafluorophenyl; 4. Ar = o-pivaloylaminophenyl; 5. Ar =
p-pivaloylaminophenyl; (depe)Ni(Me)(SAr), (depe = 1,2-bis(diethylphosphino)ethane); 7. Ar = phenyl;
8. Ar = pentafluorophenyl; 9. Ar = o-pivaloylaminophenyl; 10. Ar = p-pivaloylaminophenyl), were
synthesized via the reaction of (dppe)NiMe2 (1) and (depe)NiMe2 (6) with either the corresponding
thiol or disulfide. These complexes were characterized by various spectroscopic methods including 31
NMR, 1H NMR, 13C NMR and infrared spectroscopies and in most cases by X-ray diffraction
P
analyses. Solid state and solution measurements establish that 4 and 9 contain intramolecular N–H ◊ ◊ ◊ S
bonds. Carbonylation of the complexes 2–4, 7–10 leads to (dRpe)Ni(CO)2 and MeC(O)SAr via the
intermediacy of the acylnickel adducts, (dRpe)Ni(C(O)Me)(SAr), detected at low temperature by 31
P
NMR spectroscopy. Consistent with experimental observations, density functional theory results reveal
that the intramolecular hydrogen bond in 9 stabilizes the acylnickel adduct compared with its
non-hydrogen-bonded adduct, 10. Oxidative addition of MeC(O)SC6F5 to (dRpe)Ni(COD) followed by
spontaneous decarbonylation proceeds in variable yields generating 3 and 8.
Introduction
Acetyl coenzyme A synthase (ACS), a Ni-Fe-S metalloenzyme
found in methanogenic, acetogenic and sulfate-reducing organ-
isms, is responsible for the assembly/disassembly of acetyl coen-
zyme A from CO, methylcob(III)alamin and the thiol, CoA.1,2 The
assembly transformation allows acetogens to grow autotrophically
on one-carbon substrates, whereas the disassembly into its con-
stituent components permits methanogens to utilize acetate as an
alternate substrate in methane production.3 Anaerobic methano-
genesis accounts for the majority of methane production globally.
Thus, a detailed understanding of biological methane production
is requisite to understanding the global carbon cycle.1 Further
motivation for detailed studies of the structure and function of
ACS derives from a desire to understand the novel cofactors
utilized by archaea and their ability to promote one-carbon
transformations via the proposed intermediacy of unprecedented
organometallic species in biology, including Ni-CO, Ni-CH3 and
Ni-C(O)CH3 adducts.4
Fig. 1 Schematic representation of the A cluster. Non-protein ligand(s)
of Nip not shown.
the [Fe4S4], Nip, is ligated to three Cys residues, each bridging to
other metal ions. The donor ligands for the square planar distal
Ni, Nid, are two Cys side chain thiolates that bridge to Nip and
two amide backbone donors derived from three successive amino
acid residues, CysGlyCys. Despite the advances in the structural
biology of ACS, there has been less progress in understanding
how the protein structure encodes function, i.e. details regarding
the mechanism of acetyl CoA synthesis. The common mechanistic
scenarios6,7 invoke substrate binding and turnover at the dinickel
subcluster with the role of the [Fe4S4] limited to either it serving as a
conduit for electron transfer and/or to it regulating the electronic
character at nickel.8 Indeed, the majority of synthetic modeling
studies,9 including those from our laboratory,10–12 have targeted
nickel complexes as appropriate platforms from which to derive
chemical precedents and mechanistic understanding. Nonetheless,
analogs that incorporate cuboid clusters have been prepared13 and
remain attractive targets for synthetic and in particular, reactivity
studies.
Recent protein crystal structure reports have revealed that the
ACS active site is a Ni-Fe-S cluster of unprecedented composition
and structure, Fig. 1.5 The so-called A cluster consists of Ni2Fe4S4
organized into a cuboidal [Fe4S4] cluster linked via a bridging
Cys to a dinickel subcluster. Their very different coordination
environments distinguish the two Ni ions. The Ni proximal to
Department of Chemistry and Biochemistry, University of Delaware,
Newark, DE 19716, USA
† Electronic supplementary information (ESI) available: Fig. S-1–S-18
and Tables S-1–S-12. CCDC reference numbers 716709–716717. For ESI
and crystallographic data in CIF or other electronic format see DOI:
10.1039/b901192g
This journal is
The Royal Society of Chemistry 2009
Dalton Trans., 2009, 4359–4369 | 4359
©

The elementary steps in the ACS catalytic cycle are summarized
in Scheme 1. While the overall transformation is not strictly
a redox reaction, the donation of the methyl group from the
corrinoid protein likely requires a redox active metal site to accept
a methyl cation equivalent, i.e. methyl transfer from cobalt to
the A cluster is an oxidative addition process. Assignments of
metal ion oxidation states during catalysis remain the subject of
debate, with both Ni(I) and more recently, Ni(0),6 proposed as
the fully reduced states competent in catalysis. Indeed, studies
from these laboratories have established chemical precedents for
methyl transfer from methylcobaloxime to nickel(I)14 or nickel(0)11
acceptors. The former occurs via a radical pathway, whereas
the latter is suggested to proceed via a SN2 mechanism. The
remaining steps in ACS catalysis leading to thioester formation
are carbonylation to generate an acylnickel followed by CoA
addition/reductive elimination yielding the thioester. There are
a number of relevant precedents for these steps with monomeric
nickel complexes with leading examples provided by Yamamoto,15
Holm,16,17 Hillhouse18 and Sellmann.19 Carbonylation of alkyl-
nickel thiolates leads to CO insertion into the Ni–Me bond and
acylnickel thiolate formation. Additional CO promotes reductive
elimination of thioester with the Ni(0) fragment trapped by excess
CO. Very recently we reported the initial example of thioester
formation via carbonylation of a binuclear methylnickel,12 a model
complex of higher structural fidelity.
that suggest that these thiolate bridges are susceptible to facile
and reversible rupture, a process that leads to a terminal Cys,
a residue that would be accessible for acetylation. Second, the
nucleophilicity of Cys residues can be modulated by hydrogen-
bonding interactions. One such interaction involving a backbone
amide N–H and a Ni–Cys is found at the A cluster, Fig. 1. This
structural element would render the hydrogen-bonded thiolate less
nucleophilic. Indeed, hydrogen bonding to zinc-thiolates results in
a measurable diminution of thiolate nucleophilicity as determined
in protein and model studies.21,22 A third consideration is that
acetylation of active site Cys residues does occur and the process
is reversible such that Cys acetylation does not render the enzyme
inactive. We consider this scenario plausible based on two lines of
experimental evidence. First, ACS activation of acetyl CoA (and
by extension acetyl-Cys) occurs in methanogens.23 Second, an in
vitro assay of ACS activity involves CO incorporation into14C-
labeled acetyl CoA,24 a process that necessitates reversible C–S
bond rupture. Herein, we present synthetic studies that address
the role of hydrogen-bonding on C–S reductive elimination and
that demonstrate thioester C–S oxidative addition to nickel(0) and
place these results in the context of ACS catalysis.
Results and discussion
Synthesis of complexes
The preparation of the (dRpe)Ni(Me)(SAr) complexes was
achieved via one of two synthetic routes, each commencing with
the corresponding (dRpe)NiMe2 complex, Scheme 2. Surprisingly,
(depe)NiMe2 has not been reported previously. Thus, its synthesis
and characterization are included here. Protonolysis with ArSH
generated complexes 2, 3, 7 and 8 in good isolated yields.
This procedure follows the route employed by Yamamoto15 in
the synthesis of 2 and subsequently by Holm17 for the related
(bpy)Ni(Me)(SAr) complexes. Complexes 4, 5,25 9 and 10 were
synthesized by reaction of (dRpe)NiMe2 with the appropriate
disulfide, Ar2S2, Scheme 2. The latter alkyl-for-thiolate exchange
has been applied successfully to the preparation of zinc aryl
thiolate complexes.22 At parity of dRpe chelating ligand, the ortho-
substituted aryl disulfide reacted much more rapidly than the para
isomer. We observed a similar trend for the reactions of these
same disulfide substrates with methylzinc complexes. The basis for
these relative rates is likely of electronic origin, because, in part,
Scheme 1 General overview of ACS catalysis highlighting substrate
binding only at Nip and invoking the ‘Ni(0)’ mechanism. The nickel redox
states and the role of the [Fe4S4] cluster (not shown) remains issues of
debate.
Despite the aforementioned advances in chemical precedents for
ACS catalysis, several outstanding issues remain to be addressed.
Principle to the present report is aspects of the final step in
catalysis, i.e. the reductive C–S bond-forming step. In particular we
are interested in understanding how acyl transfer to CoA occurs
with high fidelity without acetylation of Cys residues in the A
cluster. Three possibilities are considered – the first two highlight
structural elements that serve to reduce the nucleophilicity of
Cys residues so as to direct acetylation to CoA. First, bridging
Cys thiolates as found in the A cluster are poorer nucleophiles
than terminally ligated thiolates and therefore, less susceptible to
acetylation. Thus, the positioning of the active site Cys residues
in bridging positions likely serves to reduce the propensity of
Cys acetylation during ACS catalysis. However, this hypothesis
is complicated by experimental12 and computational20 evidence
Scheme 2
4360 | Dalton Trans., 2009, 4359–4369
This journal is
The Royal Society of Chemistry 2009
©

Table 1 Solid state and solution IR data for complexes 4, 5, 9, and 10
steric crowding at the transition state would seemingly disfavor,
i.e. slow down, the reaction of the ortho isomer. If one considers
the mechanism as involving Ni–Me attack on an electrophilic
sulfur of the disulfide, Scheme 3, then H-bonding within the ortho-
substituted aryl disulfide is expected to enhance the electrophilicity
of the disulfide and increase the reaction rate. Further, consistent
with this analysis is the observation that the more electron-rich
(depe)NiMe2 reacted faster than (dppe)NiMe2 at parity of the
aryl disulfide substrate.
4
5
9
10
nN-H (cm-1)a
nC (cm-1)a
3276
1670
3281
1676
3342
1662
3374
1675
3282
1670
3283
1676
3324
1661
3360
1679
=
O
nN-H (cm-1)b
nC (cm-1)b
=
O
a Solid state, KBr. b Solution state, THF.
protons in C6D6, d = 9.88 for 4 and d = 10.02 for 9. In complexes 5
and 10, the non-H-bonded amide protons of the para substituents
are found at markedly higher field, d = 6.68 for 5 and d = 6.72
for 10. Solution (THF) and solid state FT-IR measurements also
support H-bonding in 4 and 9 with nNH features broadened and
shifted to lower energy, nNH = 3276 cm-1 for 4 and nNH = 3282 cm-1
for 9, Table 1.26 These modes are ca. 40–65 cm-1 lower in energy
than those found for the non-H-bonded 5 and 10. The similarity
between the solution and solid-state nNH energies supports the
assertion that the intramolecular H-bonding in the solid state as
determined by X-ray diffraction analyses, vide infra, is maintained
in solution. Similar differences in nNH energies between ortho and
para substituted arylthiolates were observed for monomeric zinc
complexes.22
Scheme 3
Spectroscopic properties
1
The H NMR spectra of complexes are highlighted by the Ni-
methyl resonances which occur within the narrow range, d =
-0.25 to 0.50. The derivatives with the least donating thiolate
ligands, C6F5 and ortho-pivaloylaminophenyl, contain the most
highly shielded Ni-methyl resonances. The 31P NMR spectra are
Molecular structures
2
characterized by two doublets with JPP = ~7–10 Hz for the
The geometric structures of complexes 2–4, 7–10, Fig. 2 and 3,
have been determined by single crystal X-ray diffraction methods.
Crystallographic data are collected in Table 2 with selected metric
parameters contained in Table 3. Each complex shows the expected
2
dppe derivatives and JPP = ~14–18 Hz for the depe derivatives.
Complexes 4 and 9 contain intramolecular N–H ◊ ◊ ◊ S bonds in
solution as supported by the downfield chemical shifts of these
Fig. 2 Thermal ellipsoid plots of 2, 3, 7 and 8 drawn at the 35% probability level. Hydrogen atoms and phenyl carbons of the dppe ligand (except for
the ipso carbon) have been removed. For 3, the sulfur disorder is not shown. For 7, only one molecule in the asymmetric unit is depicted.
This journal is
The Royal Society of Chemistry 2009
Dalton Trans., 2009, 4359–4369 | 4361
©

Table 2 Crystallographic data for complexes 1–4, 7–10
1
2
3
4
7
8
9
10
formula
fw
C28H30NiP2 C33H32NiP2S C33H27F5NiP2S C38H41NNiOP2S C17H32NiP2S C17H27F5NiP2S C22H41NNiOP2S C22H41NNiOP2S
487.17
581.30
671.26
680.43
monoclinic
P21/c
389.14
479.10
488.27
orthorhombic
Pbca
488.27
monoclinic
P21/c
cryst syst
space group
monoclinic monoclinic monoclinic
P21/c
orthorhombic monoclinic
Fdd2
P21/n
P21/n
P21/n
˚
a, A
11.342(5)
13.250(6)
16.491(7)
90.00
98.879(7)
90.00
9.055(6)
26.163(18)
12.560(9)
90.00
102.619(10) 94.243(7)
90.00
9.556(4)
14.530(6)
21.763(8)
90.00
9.4485(11)
15.0012(18)
24.172(3)
90.00
97.739(2)
90.00
33.934(3)
68.417(9)
6.7986(7)
90.00
90.00
90.00
9.378(3)
19.435(6)
11.641(3)
90.00
99.304(4)
90.00
17.408(3)
17.549(3)
17.680(3)
90.00
90.00
90.00
12.256(2)
11.7385(19)
17.325(3)
90.00
90.552(2)
90.00
˚
b, A
˚
c, A
a, deg
b, deg
g , deg
90.00
3
˚
V, A
2448.6(18) 2904.0(3)
3014.0(2)
4
3394.9(7)
4
15784(3)
32
2095.9(10)
4
5401.1(15)
8
2492.4(7)
4
Z
T
4
4
120
1.322
170
1.330
170
1.480
1.69–28.40
0.873
120
1.331
1.60–28.28
0.758
120
1.310
2.15–25.00
1.244
120
1.518
2.06–28.27
1.220
290
1.201
2.01–28.35
0.926
120
1.301
1.66–28.31
1.003
D
calcd, g cm-1
q range, deg
1.82–28.30 1.83–28.28
m(Mo, Ka) mm-1 0.936
0.871
Reflections
Unique
R(int)
R1
26720
5686
0.0618
0.0413
0.0972
39309
7184
0.0384
0.0367
0.0977
40744
7521
0.0646
0.0546
0.1290
38887
8172
0.0707
0.0511
0.1164
40255
6932
0.0342
0.0219
0.0525
28393
5208
0.0233
0.0245
0.0663
58983
6733
0.1890
0.0798
0.1627
29483
6195
0.0340
0.0356
0.0887
wR2
Fig. 3 Thermal ellipsoid plots of 4, 9 and 10 drawn at the 35% probability level. Hydrogen atoms and phenyl carbons of the dppe ligand (except for the
ipso carbon) have been removed. For 4, the position disorder is not depicted.
trans influence of the methyl donor as manifest in a statistically
longer Ni–P bond distance for the phosphine trans to methyl.
Carbonylation studies
˚
˚
A primary objective of this study was to examine the role
of the thiolate substituents, in particular the intramolecular
N–H ◊ ◊ ◊ S bonds on the reductive elimination of thioester from
the acylnickel thiolates. To achieve this objective we sought
to intercept and isolate the acylnickel thiolates resulting from
addition of one equiv. of CO to the methylnickel thiolates for
subsequent kinetic studies of reductive elimination. Such species
were inferred intermediates in the studies of Yamamoto15 on the
carbonylation of alkylnickel aryl thiolates and aryloxides and one
The Ni–S bond distances in 4, 2.144(1) A, and 9, 2.184(2) A
are the shortest among the series. The decrease in bond lengths
is attributed to the intramolecular N–H ◊ ◊ ◊ S bonds which, by
removing electron density from the thiolate sulfurs, serve to reduce
the destabilizing Ni dp–S pp interactions. The amide substituents
in 4 and 9 are positioned so as to ensure short N–S distances, 4,
˚
˚
2.973(4) A and 9, 3.009(6) A, consistent with solid state H-bonds.
The amide hydrogens were not located in the Fourier difference
maps.
4362 | Dalton Trans., 2009, 4359–4369
This journal is
The Royal Society of Chemistry 2009
©

◦
˚
Table 3 Selected bond distances (A) and bond angles ( ) of complexes 1–4, 7–10
Ni–C
Ni–S
Ni–P1
Ni–P2
∠ P–Ni–P
N ◊ ◊ ◊ S
1
1.977(2)
1.986(2)
1.983(2)
1.959(3)
2.1536(9)
2.1548(9)
87.23(4)
2
3
2.2016(12)
2.189(4)
2.1366(11)
2.1251(11)
2.2348(15)
2.1975(10)
87.42(3)
87.34(3)
2.2388(18)a
2.1443(11)
2.008(4)a
4
2.092(4)
2.1442(9)
2.2007(9)
87.34(3)
2.973(4)
3.009(6)
2.158(14)b
1.965(2)
7
2.2037(9)
2.2082(5)
2.1836(17)
2.2200(6)
2.1196(9)
2.1266(5)
2.1198(17)
2.1146(6)
2.1967(6)
2.1867(6)
2.191(2)
88.75(2)
87.25(2)
87.90(8)
88.32(2)
8
1.9717(14)
1.966(6)
1.9755(19)
9
10
2.1874(6)
a S is crystallographically disordered; hence, two Ni–S distances are reported. b C is crystallographically disordered; hence, two Ni–C distances are
reported.
example was isolated by Holm.17 However, exposure of each of the
complexes reported here, 2–4, 7–10, to one equiv. of CO at ambient
temperature did not yield the desired acylnickel thiolates (except
for in situ formation of a small amount 8, vide infra). Rather
a mixture of starting material, (dR¢pe)Ni(CO)2, and thioester
was generated. The latter species resulted from CO-promoted
reductive elimination. In all cases, exposure to 1 atm. of CO led
to clean conversion to (dR¢pe)Ni(CO)2 and the corresponding
thioester in good to excellent yields. As these observations were
consistent with instability of the targeted acylnickel thiolates
relative to both reductive elimination and decarbonylation (i.e.
reversible carbonylation), the stoichiometric addition of CO was
conducted in situ at -78 ◦C. Indeed, these conditions afforded the
acylnickel thiolate complexes, to varying degrees, as ascertained
by 31P NMR spectral analyses (Fig. S-6 to S-12†). The extent of
acylnickel thiolate formation was sensitive to the identity of the
diphosphine and arylthiolate ligands. The derivatives containing
the more electron rich depe chelating ligands yielded a greater
extent of acylnickel thiolate at parity of thiolate donor, e.g.
4 yielded ~25% acylnickel, whereas 9 yielded ~55% acylnickel.
Thus the more electron rich metal center stabilizes the acylnickel
thiolate intermediate. In regard to the influence of the thiolate
substituent, the complexes with the least electron-donating arylthi-
olates, namely those with C6F5 and the ortho-pivaloylaminophenyl
substituents, formed the acylnickel thiolates to the greatest degree,
e.g. 9 yielded ~55% acylnickel, whereas 10 yielded ~40% acylnickel.
The derivatives containing the parent phenyl or electron rich
para-pivaloylaminophenyl substituents yielded small amounts of
acylnickel intermediates, even at -78 ◦C. In contrast, the room
temperature spectra revealed that the combination of depe and
C6F5 substituents led to formation of small amounts, ca. 15–20%,
of (depe)Ni(C(O)Me)(SC6F5). This trend is in accord with the
assertion that the least electron-rich (or least nucleophilic) thiolate
is least prone to undergo spontaneous reductive elimination, a
point supported by computational studies (vide infra).
The mechanism of carbonylation
The migratory insertion of CO into a M–R bond is among
the most thoroughly studied elementary steps in organotransi-
tion metal chemistry. At square planar platinum group metals
associative and dissociative pathways often compete, with the
former generally favored in nickel complexes.29 CO addition
yielding a five-coordinate species poised for migratory insertion
competes with a dissociative pathway in which CO adds to a
three-coordinate T-shaped adduct formed via ligand loss. In the
present context ligand dissociation would most probably entail
thiolate loss as the chelating diphosphines are much less prone
to dissociation. Thiolate exchange is facile in benzene solution as
evidenced by formation of all four possible species upon mixing
equimolar concentrations of 2 and 8. The equilibrium constant,
Keq = [2][8]/[3][7] = 1.2, indicating a slight preference for the
formation of the complexes matching the more electron releasing
diphosphine with the more electron-withdrawing arylthiolate.
To further evaluate the factors that influence the relative stability
of the acylnickel thiolates, the energies of the relevant species
along a reaction sequence commencing with the methylnickel
thiolates were examined by density functional theory (DFT)
methods (B3LYP). Specifically, the relative energetics of stepwise
carbonylation to the acylnickel thiolate, then to the products
(dRpe)Ni(CO)2 and thioester, were determined for 9 and 10. In
each case, the full molecule was calculated with results depicted in
Fig. 4. The overall reactions are exergonic by 24.4 kcal/mol for 9
and 21.7 kcal/mol for 10. The acylnickel thiolate resulting from
carbonylation of 9 is 7.1 kcal/mol lower in energy than 9 + CO. In
comparison, the carbonylation of 10 to the acylnickel thiolate is
only favored by 3.7 kcal/mol (relative to 10 + CO). In other words,
the acylnickel intermediate derived from 9 is 3.3 kcal/mol more
stable than that derived from 10. These computational results are
in accord with the experimental observations that the acylnickel
complex derived from 9 is more stable than that derived from 10.
To quantitatively assess the impact of hydrogen bonding on
the relevant frontier molecular orbitals, a Mulliken population
analysis was performed on 9, 10, and the respective acylnickel
counterparts formed upon addition of CO. The analysis agrees
with the qualitative predictions noted previously. Specifically, the
ortho substituent H-bonding proton is orientated towards the filled
S p orbital, which is engaged in a Ni–S p anti-bonding interaction,
Fig. 5. The H-bonding interaction withdraws electron density
Carbonylation of alkyl nickel complexes containing aryloxo
and arylthiolato (including 2) has been extensively studied.15,27,28
In general, exposure of solutions of the nickel complexes to an
atmosphere of CO resulted in conversion to the corresponding
aryl ester or aryl thioester and nickel(0), e.g. L2Ni(CO)2, in
good to excellent yields. In only one of these reports, a study
of (bpy)Ni(Me)(SAr) complexes was an intermediate acyl species
isolable.17
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The Royal Society of Chemistry 2009
Dalton Trans., 2009, 4359–4369 | 4363
©

Fig. 4 The relative energies of DFT computed structures along the associative carbonylation reaction trajectory for complexes 9 (red) and 10 (black).
Energies are in kcal/mol. Transition state energies were not calculated and are shown as arbitrary.
from this orbital resulting in a more covalent Ni–S interaction,
reflected in increased metal d character in the relevant orbitals
as illustrated in Table 4, and shorter Ni–S distances reflected in
the crystallographically derived structures. In the non-H-bonded
case of 10, the S:Ni ratio for the bonding (S p + Ni d, HOMO-7)
and anti-bonding (S p–Ni d, HOMO) are 23:63% and 64:23%
respectively. In contrast, in the H-bonded case of molecule 9,
the bonding (HOMO-6) and anti-bonding (HOMO) S:Ni ratios
are 45:43% and 29:61% respectively. The drastically higher S
character in the non H-bonded HOMO results in a significantly
more nucleophilic S thiolate, and thus, a more favorable reductive
elimination. The results for the acylnickel complexes follow the
same trend.
We also computed the energies of species resulting from
association of CO to 9 and 10 respectively, as plausible five-
coordinate intermediates for the carbonylation reaction. In these
Table 4 Mulliken population analysis from solvated single-point hybrid DFT calculations
molecule
MO
E (eV)
description
S (%)
Ni (%)
rest (%)
9
124
131
131
137
125
131
131
138
-5.539
-4.240
-5.579
-4.388
-6.506
-4.936
-5.435
-3.971
S p + Ni d
Ni d - S p
S p + Ni d
Ni d - S p
S p + Ni d
Ni d - S p
S p + Ni d
Ni d - S p
45.85
29.32
30.79
31.85
23.38
64.43
38.28
38.89
42.97
61.31
50.85
55.39
63.21
22.83
39.86
36.17
11.18
9.38
(depe)Ni(COMe)(o-pabt)
10
18.36
12.76
13.42
12.74
21.86
24.94
(depe)Ni(COMe)(p-pabt)
4364 | Dalton Trans., 2009, 4359–4369
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The Royal Society of Chemistry 2009
©

Fig. 5 Isosurface plots (isodensity value 0.05) of Ni–S p and p* interactions from solvated single-point hybrid DFT calculations.
structures CO occupies an apical position of the square pyramid.
The CO adduct derived from 9 is destabilized by 1.2 kcal/mol
relative to the corresponding adduct derived from 10. This trend
is in agreement with the notion that the metal center in 9 is less
electron rich because the intramolecular H-bonding more than
compensates for the electron-releasing ability of the pivaloylamino
substituent. Thus, in the associative carbonylation mechanism the
slightly higher energy of the five-coordinate intermediate and more
stabilized acylnickel intermediate both contribute to stabilize the
acylnickel adduct derived from 9 relative to the acylnickel derived
from 10.
the acylnickel thiolates consistent with sequential oxidative addi-
tion followed by decarbonylation to the more stable alkylnickel
thiolates. In addition to providing insights into ACS catalysis,
this decarbonylative C–S activation represents a transformation
of some synthetic utility.32
One of the enzymatic assays for ACS activity entails CO
exchange into 14C-labeled acetyl coenzyme A, eqn (1).24
ACS
ꢂꢀꢀꢀ
Me14C(O)SCoA + CO
MeC(O)SCoA + 14 CO
(1)
ꢀꢀꢀꢀꢁ
The reversibility is not surprising given that the acetogens
utilize ACS to disassemble acetyl coenzyme A, i.e. the reaction is
catalyzed in the reverse direction. The exchange reaction demands
reversibility of each step in ACS synthesis. Significantly, reversible
thioester formation affords a pathway for the enzyme to correct
erroneous generation of acetyl-Cys at the A cluster active site. The
affected Cys would be deacetylated with subsequent acetylation
of CoA leading to product.
Thioester oxidative addition to Ni(0)
Given the potential role of Ni(0) in ACS catalysis6 and its
ubiquitous role in organometallic cross coupling reactions,30 we
sought to establish oxidative addition of thioesters to Ni(0). In the
latter setting, there is precedent for the use of thioesters as reagents
in nickel cross-coupling reactions under Mukaiyama conditions
with thioester oxidative addition to nickel(0) hypothesized as the
first step in catalysis.31 Addition of MeC(O)SC6F5 or MeC(O)SPh
to (dRpe)Ni(COD) generated in situ produced the corresponding
alkylnickel thiolates in variable yields, 2 (7%), 3 (37%), 7 (50%), and
8 (62%). In the latter three reactions, the byproducts (dppe)2Ni and
(dppe)Ni(CO)2 were also identified. Clearly, the more electron rich
(depe)Ni fragment facilities the oxidative addition by stabilizing
the Ni(II) state. The C6F5 substituent of the thioester renders the
C–S bond more susceptible to cleavage. Reactions conducted at
low temperature revealed initial formation of (variable amounts)
Summary and conclusions relevant to ACS catalysis
The objectives of these studies were two-fold. First, we sought
to quantitatively establish the effect of intramolecular N–H ◊ ◊ ◊ S
bonds on the reductive elimination of thioesters from acylnickel
thiolates via kinetic studies. Thus, a series of (dRpe)Ni(Me)(SAr)
complexes were prepared including derivatives with pivaloylamino
installed in ortho and para positions of the arylthiolate ring. The
former isomers contain intramolecular H-bonds as deduced by
solution and solid-state measurements. However, stoichiometric
carbonylation did not lead to clean conversion to the desired
This journal is
The Royal Society of Chemistry 2009
Dalton Trans., 2009, 4359–4369 | 4365
©

acylnickel thiolates precluding detailed kinetic experiments.
Rather, a mixture of species resulted indicating competitive
formation of the ‘over-carbonylated’ reductive elimination
products, (dRpe)Ni(CO)2 and thioester, eqn (2). This is somewhat
surprising given the accessibility and stability of analogous
complexes, (bpy)Ni(C(O)Me)(SAr). Low temperature 31P NMR
studies revealed that the acylnickel thiolates are indeed inter-
mediates on the path to thioester production. The generation of
these intermediates was sensitive to the identity of the arylthiolate
procedure37 with addition of 1 eq. Et3N. (Py)4NiCl228 was prepared
via addition of pyridine to a suspension of anhydrous NiCl2 in ethyl
ether. The resulting blue solid was isolated and washed with ethyl
ether. Pyridine, thiophenol, pentafluorobenzenethiol, and methyl
lithium were purchased and used without further purification.
˚
Thiophenol was dried over 5 A molecular sieves. Solvents were
dried via passage through activated alumina columns and sub-
sequently degassed by passing a stream of nitrogen. Deuterated
solvents were purchased from Cambridge Isotopes and dried over
˚
substituent, with the derivatives containing
a
H-bonded
5 A molecular sieves. Microanalyses were performed by Columbia
thiolate donor or electron-withdrawing C6F5 substituents more
stable than the Ph or para-pivaloylaminophenyl derivatives. The
relative stabilities of the ortho- and para-pivaloylaminophenyl
acylnickel derivatives were supported by DFT analyses.
Analytical Services, Tucson, AZ.
Physical measurements
NMR spectra were recorded on a 400 MHz Bruker DRX
spectrometer. Proton chemical shifts were referenced to the
residual proton peak of NMR solvent. Phosphorous chemical
shifts were referenced to the 85% H3PO4 in D2O external standards.
Infrared spectra were measured using Mattson Genesis series
FTIR spectrometer.
CO
2CO
ꢀꢀꢀꢁ
ꢂꢀꢀꢀ
(dRpe)Ni(Me)(SAr)
(dRpe)Ni(C(O)Me)(SAr) æææÆ
(2)
(dRpe)Ni(CO)2 + MeC(O)SAr
The reductive elimination of thioester is promoted by addi-
tion of an additional donor ligand, in this case CO. This has
been most clearly established by addition of excess CO to the
isolable acyl nickel complex (bpy)Ni(C(O)Me)(SAr) which leads
to (bpy)Ni(CO)2 and thioester.17 This begs the question of what
drives thioester C–S bond formation in ACS catalysis. As addition
of CO appears to be tightly regulated by the enzyme,33 it is unlikely
that addition of this ligand is employed to promote thioester
formation. Two scenarios are considered. First, CoA may directly
attack the acylnickel intermediate without prior formation of
a Ni–thiolate bond. In this case a coordination site for CoA
binding is not required. Alternatively, reductive elimination could
be driven by (reversible) formation of a Ni–SCys bond. Recent
experimental12 and computational20 studies have highlighted the
possibility of bridging Cys hemi-lability in the mechanism of ACS
synthesis. A clear synthetic precedent for the latter path remains
to be established and would be of some interest.
The second objective of the report was to demonstrate thioester
oxidative addition to Ni(0) as this transformation (i) lends further
support for the potential role of Ni(0) in ACS by highlighting
the reversibility of C–S bond formation via the Ni(0)/Ni(II)
redox couple and (ii) bears on the possibility of acetylated-Cys
formation and repair at the ACS active site cluster. Addition
of MeC(O)SC6F5 to (dRpe)Ni(COD) proceeded rapidly to the
corresponding alkylnickel thiolate with concomitant formation of
Ni(0) products, (dRpe)2Ni and (dRpe)Ni(CO)2.
The syntheses of the methylnickel thiolates were conducted
under conditions of excess.
(dppe)Ni(Me)(SC6F5), 3. A solution of C6F5SH (95 mL,
0.7 mmol) in toluene (10 cm3) was added◦to a solution of 1
(0.487 g, 1.0 mmol) in toluene (50 cm3) at -78 C. The mixture was
stirredfor 2hwhilethe temperature graduallyincreasedtoambient
temperature during which time a yellow solid precipitated. Pentane
(50 cm3) was added to complete the precipitation. The supernatant
was removed via cannula and the solid was washed with ethyl ether
(3 ¥ 30 cm3). The solid was dried under vacuum overnight to give 3
as an orange-yellow powder (0.30 g, 64%). X-Ray quality crystals
were obtained from ethyl ether diffusion into a concentrated
THF solution. Mp 194–196 ◦C (THF/ethyl ether). (Found: C,
59.4; H, 4.1. C33H27NiP2SF5 requires C, 59.1; H, 4.1%). dP
(162 MHz; C6D6, H3PO4) 48.4, 61.5 (d, JPP 10.6, PCH2CH2P); dC
(100 MHz; C6D6, C6D6) 5.60 (dd, JPC 59.0 and JP¢C 27.8, NiCH3),
25.80, 29.10 (PCH2CH2P), 128.90, 130.70, 130.12, 130.78, 130.95,
131.27, 131.40, 131.56, 133.54, 133.69; dH (400 MHz; C6D6, C6D6)
0.26 (3H, dd, JPH 6.7 and JP¢H 4.0, NiCH3), 1.53–1.72 (4H, m,
PCH2CH2P), 6.97 (7H, m), 7.06 (5H, m), 7.51 (4H, m) and 7.84
(4H, m) for CH2P(C6H5)2).
(dppe)Ni(Me)(o-pabt), 4. A solution of o-pivaloylamino-
benzenedisulfide (o-pabd) (0.250 g, 0.6 mmol) in toluene (20 cm3)
was added dropwise to a solution of 1 (0.487 g, 1.0 mmol) in
toluene (50 cm3) at -78 ◦C. The mixture was stirred for 2 h
while the temperature gradually increased to ambient temperature
during which time a yellow solid precipitated. Ethyl ether (50 cm3)
was added to complete the precipitation. The supernatant was
removed via cannula and the solid was washed with ethyl ether
(2 ¥ 30 cm3). The solid was dried under vacuum overnight to give
an orange-yellow powder (0.33 g, 80%). Orange-yellow crystals
were obtained from ethyl ether diffusion into a concentrated THF
solution. (Found: C, 66.9; H, 5.8; N 1.7. C38H41NiP2NSO requires
C, 67.1; H, 6.1; N 2.1%). nmax (KBr)/cm-1 3276 (m, NH) and 1660
(s, CO); nmax (THF)/cm-1 3281 (m, NH) and 1676 (s, CO); dP
(162 MHz; C6D6, H3PO4) 47.3, 60.2 (d, JPP¢ 7.5); dC (100 MHz;
C6D6, C6D6) 6.70 (dd, JPC 57.6 and JP¢C 26.6, Ni-CH3), 28.43 (s,
tBu), 26.10, 29.40 (PCH2CH2P), 40.39 (s, C(Me)3), 118.38, 122.48,
Experimental
Synthesis
All manipulations were conducted in a nitrogen-filled glove box
or on a Schlenk line under nitrogen. 215 was synthesized following
the literature procedure. ortho-Pivaloylaminobenzene disulfide
and para-pivaloylaminobenzene disulfide were synthesized from
the corresponding amino disulfides and pivaloyl chloride as de-
35
scribed previously.34 (tmeda)NiMe2 and (dppe)NiMe2(1)36 were
synthesized via a modification of the procedure reported28 for
(dippe)NiMe2 in which dippe was replaced with tmeda and dppe,
respectively. Thioesters, CH3C(O)SC6H5 and CH3C(O)SC6F5,
were synthesized via a slight modification of the reported
4366 | Dalton Trans., 2009, 4359–4369
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The Royal Society of Chemistry 2009
©

126.35, 128.77, 130.50, 130.64, 131.36, 132.10, 132.45, 133.40,
136.80; dH (400 MHz; C6D6, C6D6) 0.11 (3 H, dd, JPH 7.4 and JP¢H
4.2, NiCH3), 0.82 (8H, m), 1.04 (10H, m), (CH2P(C2H5)2), 1.33,
1.68 (m) (PCH2CH2P), 7.03 (1H, t, 7.0, p-SC6H5), 7.17 (2H, d,
7.6, m-SC6H5), 7.93 (2H, d, 7.6, o-SC6H5).
133.60, 142.13, 175.20 (s, NHC(O)); dH (400 MHz; C6D6, C6D6)
t
0.23 (3H, dd, JPH 7.3 and JP¢H 4.1, NiCH3), 1.31 (9H, s, Bu),
1.59–1.84 (4H, m, PCH2CH2P), 6.79 (1H, td, J1,2 7.2 and J1,3
4.2, p-(C6H4)S), 9.20 (1H, d, J1,2 7.2, o-(C6H4)N)) 7.00 (6H, m),
7.10 (7H, m), 7.48 (4H, m), 7.8 (5H, m(CH2P(C6H5)2) 9.88 (1H,
s, NH).
(depe)Ni(Me)(SC6F5), 8. A solution of C6F5SH (200 mL,
1.5 mmol) in ethyl ether (10 cm3) was added dropwise to a solution
◦
of 6 (0.600 g, 2.03 mmol) in ethyl ether (20 cm3) at -78 C. The
(dppe)Ni(Me)(p-pabt), 5. A solution of p-pivaloylamino-
benzenethiol (0.230 g, 1.04 mmol) in THF (10 cm3) was added
dropwise to a solution of 1 (0.695, 1.42 mmol) in THF (50 cm3).
The mixture was stirred overnight yielding a brown solution.
The solution was taken into dryness, and washed with ethyl
ether (3 ¥ 20 cm3). The solid was dissolved in minimum volume
of THF and precipitated with ethyl ether. Collected yellow
solid was dried under vacuum giving crude 5 (0.216 g, 41%)
contaminated with (dppe)2Ni. Repeated recrystallizations from
THF/ethyl ether yielded spectroscopically pure 5. (Found: C,
66.1; H, 6.0; N 1.9. C38H41NiP2NSO requires C, 67.1; H, 6.1;
N 2.1%). nmax(KBr)/cm-1 3342 (m, NH) and 1662 (s, CO);
mixture was stirred for two hours while the temperature gradually
increased to ambient temperature. The resulting yellow solid was
precipitated following the addition of pentane and subsequently
washed with additional pentane (3 ¥ 20 cm3). The solid was dried
under vacuum overnight giving 8 (0.431 g, 60%) as a yellow solid.
Yellow crystals were obtained from slow evaporation of ethyl ether.
◦
Mp, 120–122 C (ethyl ether) (decomposed) (Found: C, 43.4; H,
5.5. C17H27NiP2SF5 requires C, 42.6; H, 5.7%). dP (162 MHz; C6D6,
H3PO4) 59.4, 68.8 (d, JPP¢ 17.7); dC (100 MHz; C6D6, C6D6) -0.73
(dd, JPC 65.1, JP¢C 30.5, NiCH3), 8.90, 10.94 (CH2P(CH2CH3)2),
18.55, 18.85 (CH2P(CH2CH3)2), 21.33, 24.62 (PCH2CH2P), 121.0,
127.62, 136.80, dH (400 MHz; C6D6, C6D6) -0.26 (3H, dd, JPH 6.6,
n
max(THF)/cm-1 3374 (NH) and 1675 (CO); dP (162 MHz; C6D6,
JP¢H 4.2, NiCH3), 1.62 (m), 1.30 (m) (CH2P(C2H5)2); 0.77 (m), 1.02
H3PO4) 60.2, 47.0 (d, JPP 7.8 PCH2CH2P), dC (100 MHz; C6D6,
C6D6) 6.57 (dd, JPC 58.8 and JP¢C 25.7, NiCH3), 27.55 (s, tBu), 29.45
(PCH2CH2P), 39.26 (s, C(Me)3), 119.52, 128.53, 130.31, 130.41,
130.96, 131.53, 133.65, 133.85, 137.10, 174.40 (s, NHC(O)); dH
(400 MHz; C6D6, C6D6) 0.49 (3H, dd, JPH 7.8 and JP¢H 4.2,
NiCH3), 0.97 (9H, s, tBu) 1.64–1.89 (4H, m, (PCH2CH2P),
6.90–7.02 (16H, m), 7.10 (4H, m), for (CH2P(C6H5)2, 6.74
(s, NH).
(m) (CH2P(C2H5)2).
(depe)Ni(Me)(o-pabt), 9. A solution of o-pabd (0.430 g,
1.03 mmol) in THF (10 cm3) was added dropwise to a solution
of 6 (0.475 g, 1.6 mmol) in THF (20 cm3). The mixture was stirred
for four hours. The volatiles were removed under vacuum and
the solid was washed with ethyl ether (4 ¥ 20 cm3). The product
(0.400 g, 88%), was obtained as a yellow solid. Orange-yellow
crystals were obtained from ethyl ether diffusion to a concentrated
THF solution. Mp, 166–168 ◦C (THF/ethyl ether) (decomposed)
(Found: C, 54.6, H, 8.3, N, 2.9; C22H41NiP2SNO: required C,
54.1, H, 8.5, N, 2.9%). nmax(KBr)/cm-1 3282 (NH) and 1670 (CO);
(depe)NiMe2, 6. This new compound was synthesized as
follows. A solution of depe (470 mL, 2 mmol) in ethyl ether (5 cm3)
was added to a suspension of (tmeda)NiMe2 (0.408 g, 2 mmol)
in ethyl ether (40 cm3) at -78 ◦C. The mixture was stirred for
an hour at -78 ◦C and an hour at ambient temperature during
which the color of the suspension turned to from light green
to yellow. The solution was taken to the dryness. The product
was extracted with ethyl ether (4 ¥ 25 cm3) and filtered through
Celite. Partial evaporation of the volatiles produced a bright yellow
microcrystalline solid (0.55 g, 93%). dP (162 MHz; C6D6, H3PO4)
62.1 (s, CH2PEt2); dC (100 MHz; C6D6, C6D6) 1.78 (dd, JPC 76.3,
JP¢C 20.2, NiCH3), 9.13 (s, (CH3CH2)2P), 18.20 ((CH3CH2)2P),
23.53 (PCH2CH2P); dH (400 MHz; C6D6, C6D6) 0.48 (6H, dd, JPH
10.4, JP¢H 4.4, NiCH3); 0.91 (12H, m P(CH2CH3)2), 1.00 (4H, dd,
JPH 8.0, JP¢H 3.2, PCH2CH2P) 1.26, 1.51 (8H, m, P(CH2CH3)2).
n
max(THF)/cm-1 3283 (NH) and 1676 (CO); dP (162 MHz; C6D6,
H3PO4) 57.4, 66.4 (d, JPP 13.7); dC (100 MHz; C6D6, C6D6) 1.08
(dd, JPC 61.0, JP¢C 29.9, NiCH3), 8.10 (P(CH2CH3)2), 17.86, 18.81
(P(CH2CH3)2), 21.40, 23.70 (PCH2CH2P), 28.42, 118.36, 122.45,
125.87, 136.68, 142.23, 175.40 (s, NHC(O)); dH (400 MHz; C6D6,
C6D6) -0.10 (3 H, dd, JPH 7.0, JP¢H 3.9, NiCH3), 1.45 (s, tBu), 0.75
(m), 0.86 (m), 0.96 (m), 1.26 (m) (CH2P(C2H5)2); 0.77 (m), 1.02 (m)
(PCH2CH2P), 6.89 (1H, d, J1,2 7.8 and J1,3 6.7, p-(C6H4)S), 7.88
(1H, d, J1,2 7.3, o-(C6H4)S)), 9.30 (1H, d, J1,2 8.4, o-(C6H4)N)),
10.02 (s, NH).
(depe)Ni(Me)(p-pabt), 10. A solution of p-pabd (0.280 g,
0.67 mmol) in THF (10 cm3) was added drop-wise to a solution of
6 (0.295 g, 1.0 mmol) in THF (20 cm3). The mixture was stirred for
four hours. The volatiles were removed under vacuum and the solid
was washed with ethyl ether (3 ¥ 20 cm3). The product (0.312 g,
95%) was obtained as a yellow solid. Orange crystals were obtained
from slow evaporation of a concentrated THF solution. Mp, 150–
152 ◦C (THF/ethyl ether) (decomposed) (Found: C, 54.4, H,
8.5, N, 2.9; C22H41NiP2SNO: required C, 54.1, H, 8.5, N, 2.9%);
(depe)Ni(Me)(SPh), 7. A solution of thiophenol (70 mL,
0.68 mmol) in ethyl ether (5 cm3) was added dropwise to a solution
of 6 (0.290 g, 1.0 mmol) in ethyl ether (20 cm3) at -78 ◦C. The
mixture was stirred for two hours while the temperature gradually
increased to ambient temperature. The mixture was taken into
dryness and washed with cold pentane (50 cm3). The solid was
dissolved in ethyl ether (20 cm3). Slow evaporation of the volatiles
produced an orange crystalline solid (0.160 g, 60%). X-Ray quality
yellow crystals were obtained from slow evaporation of ethyl ether.
Mp, 98–100 ◦C (ethyl ether) (decomposed) (Found: C, 53.3; H,
8.2. C17H32NiP2S requires C, 52.5; H, 8.3%). dP (162 MHz; C6D6,
H3PO4) 66.6, 58.8 (d, JPP¢ 15.3); dC (100 MHz; C6D6, C6D6) 0.70
(dd, JPC 65.0, JP¢C 31.7, NiCH3), 9.05 (CH2P(CH2CH3)2), 18.15,
18.84 (P(CH2CH3)2), 21.47, 24.75 (PCH2CH2P), 123.30, 127.62,
n
max(KBr)/cm-1 3324 (m, NH) and 1661 (s, CO); nmax(THF)/cm-1
3360 (NH) and 1679 (CO); dP (162 MHz; C6D6, H3PO4) 59.0, 66.3
(d, JP-P 14.8); dC (100 MHz; C6D6, C6D6) 0.99 (dd, JPC 62.2, JP¢C
29.2, Ni-CH3), 9.01 (P(CH2CH3)2), 18.16, 18.79 (P(CH2CH3)2),
27.56 (s, tBu), 21.58, 24.70 (PCH2CH2P), 39.26 (s, C(Me)3), 119.49,
135.01, 136.93, 174.79 (s, NHC(O)); dH (400 MHz; C6D6, C6D6)
t
0.12 (3H, dd, JPH 7.3, JP¢H 4.2, NiCH3), 1.0 (s, Bu), 0.83 (m),
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The Royal Society of Chemistry 2009
Dalton Trans., 2009, 4359–4369 | 4367
©

Table 5 Percent spectroscopic yields of (dRpe)Ni(Me)(SAr) in NMR
1.04 (m) (CH2P(C2H5)2), 1.34 (m), 1.68 (m) (PCH2CH2P), 6.76
(s, NH), 7.52 (2H, d, JPH 8.30, o-(C6H4)S), 7.86 (2H, d, JPH 8.30,
m-(C6H4)S).
scale reactions
dppe (%)
depe (%)
CH3COSPh
CH3COSC6F5
7
37
50
62
Thiolate exchange
Complexes 2 and 8 (0.2 mmol each) were dissolved in equal
volumes of C6D6 and mixed in an NMR tube. 31P NMR and
1H NMR spectra were recorded at ambient temperature against
an external standard (H3PO4 in D2O), confirming the presence
of the four different species, 2, 3, 7, and 8. Keq was determined
via 31P NMR signal integration vs. the external standard. Equi-
librium was also achieved by mixing 3 and 7 in an analogous
fashion.
Gaussian0338 using the BP86 functional in the gas phase with
Ahlrich’s triple-z with polarization (TZVP) basis set on Ni, P, and
S and split valence with polarization (SVP) on O, N, C, and H.
The calculations were performed with a fine integration grid and
tight SCF cutoffs to reduce numerical noise as restricted singlets,
except in the cases of 5-coordinate species, which were calculated
within the unrestricted formalism as triplets. To ensure stationary
points on the models respective potential energy surfaces had been
reached and to provide thermal corrections, analytical frequency
calculations were performed yielding no imaginary frequencies.
Single point calculations were then performed on the optimized
coordinates using the hybrid functional B3LYP and TZVP basis
set on all atoms to provide accurate energetics. An ultrafine
integration grid and tight SCF cutoffs were employed. The single
point calculations included CPCM to account for solvation effects.
The solvent parameters chosen were those of THF. Final energies
are the sum of the thermal parameters at 298.15 K from the
analytical frequency calculations and the solvation corrected SCF
Sequential CO addition to 3, 4, 7–10
0.02 mmol of the methylnickel complex was dissolved in THF
(1.0 mL) and transferred to a NMR tube. An external standard
(H3PO4 in THF) in a sealed capillary tube was inserted into the
NMR tube, which was then sealed with a rubber septum. The
contents of the NMR tube were frozen in liquid nitrogen and
the air in the headspace was evacuated under vacuum. After
warming to -78 ◦C, initial 31P NMR spectra were recorded at
202 K. Aliquots of dry CO (0.01 mmol, 220 mL) (passed through
(i) a 0.1M solution of alkaline pyrogallol contained in a U-tube
at -78 ◦C, and (ii) a tube of Drierite desiccant) were added to the
NMR tube at -78 ◦C using a gas tight syringe. Signal integrations
were normalized to the external standard.
energy from the hybrid single point calculations (ETOTAL = EB3LYP
+
E
SOLV + ETHERM - TS). Mulliken population analysis was performed
using QMForge.39
X-Ray structural solution and refinement
Addition of MeC(O)SC6F5 to (dRpe)Ni(COD)
Data were collected on a Bruker-AXS APEX diffractometer
Preparative scale reaction: dppe (0.08 g, 0.2 mmol) in toluene
(10 cm3) was added dropwise to a toluene solution of Ni(COD)2
(0.055 g, 0.2 mmol) at -78 ◦C. Then, a toluene solution of
MeC(O)SC6F5 (0.048 g, 0.2 mmol) was added to the orange-yellow
reaction mixture at -78 ◦C. The reaction mixture was stirred at
equipped with graphite monochromated Mo Ka radiation (l =
˚
0.7107 A). The unit cell parameters and orientation matrices
were determined by gathering reflections from three sets of 15–
20 frames using 0.3◦ w scans. The systematic absences, together
with the unit cell parameters, in the diffraction data are uniquely
consistent with the reported space groups. All structure factors,
anomalous dispersion coefficients, and the applied SADABS
absorption correction program are contained in various versions
(5.1–6.12) of SHELXTL program library.40 Two symmetry unique
but chemically identical molecules of 7 were located in the
asymmetric unit. Compounds 2 and 4 display level B alerts in
checkCIF (http://checkcif.iucr.org) for failing the Hirshfeld test
for Ni–S and Ni–P, respectively, however there is no ambiguity
as to atom identities based on synthesis. Compound 9 displays
level A and B alerts which are attributable to the high thermal
activity of the molecule. Attempts to collect diffraction data below
290 K for 9 failed because of an irreversible phase change. The
structure of (dppe)Ni(CO)2, a known compound,41 is reported in
the electronic supplementary information (ESI).† The absolute
structure parameter of (dppe)Ni(CO)2 refined to nil indicating
the true hand of the data was established. The carbon atoms
in the ethylene backbone of dppe are disordered and were
not stable to anisotropic refinement. All other non-hydrogen
atoms were anisotropically refined using the conventional full-
matrix least-squares method. All hydrogen atoms were treated
as idealized contributions. CCDC reference numbers 716709–
716717.†
◦
-78 C for two hours and subsequently at ambient temperature.
The solvent was removed under vacuum, and the solid was dried
under vacuum overnight. The product mixture was obtained as
a yellow solid (0.094 g, 70%). The 31P NMR spectra in C6D6
revealed that the product is a mixture of 46% Ni(dppe)2 and
40%(dppe)Ni(Me)(SC6F5)and 14%(dppe)Ni(CO)2. Alternatively,
reactions were performed under similar conditions in situ in
an NMR tube as follows: A solution of dRpe (0.02 mmol)
in THF (0.5 cm3) was added to a THF solution (0.5 cm3)
of Ni(cod)2 (0.02 mmol) in a NMR tube containing an ex-
ternal standard (0.02 M H3PO4 in D2O) in a sealed capillary
◦
at -78 C. Then, a THF solution (0.5 cm3) of MeC(O)SAr
(0.02 mmol) was added via syringe. The 31P NMR spectra recorded
at room temperature revealed, in addition to the (dRpe)Ni-
(Me)(SAr), byproducts - Ni(dRpe)2, (dRpe)Ni(CO)2 with (dRpe)-
Ni(SAr)2.
The percent spectroscopic yields of (dRpe)Ni(Me)(SAr) in
NMR scale reactions are given in Table 5.
Density functional theory computations
Computational models of 9 and 10 were constructed based
on crystallographic coordinates. The models were optimized in
4368 | Dalton Trans., 2009, 4359–4369
This journal is
The Royal Society of Chemistry 2009
©

L. Rheingold, A. Marchaj and J. R. Norton, J. Am. Chem. Soc., 1997,
119, 1648–1655.
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These studies were supported by the NIH (GM59191). Compu-
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by the Bioinformatics Center of the University of Arkansas for
Medical Sciences (NIH Grant P20 RR-16460 from the IDeA
Networks of Biomedical Research Excellence (INBRE) Program
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