Mechanistic Study of Nickel-Catalyzed Reductive Coupling of Ynoates and Aldehydes

Article abstract of DOI:10.1021/acs.joc.7b00483

In this work, (1,5-hexadiene)Ni(SIPr) (SIPr = 1,3-bis(2,6-diisopropylphenyl)imidazolidin-2-ylidene) is used in place of Ni(COD)₂/SIPr·HBF₄/KO^tBu (COD = 1,5-cyclooctadiene) as a more robust catalyst for regioselective reductive coupling of ynoates and aldehydes with triethylsilane. The catalytic reaction of ethyl 3-(trimethylsilyl)propiolate and methyl 4-formylbenzoate shows first-order dependence on aldehyde and catalyst concentrations, inverse first-order dependence on [ynoate], and no dependence on [silane]. The kinetics data, coupled with deuterium-labeling experiments, support a mechanism involving dissociation of the ynoate from a catalytically dormant nickelacyclopentadiene intermediate prior to turnover-limiting formation of a catalytically active nickeladihydrofuran.

Full text of DOI:10.1021/acs.joc.7b00483

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Article
A Mechanistic Study of Nickel-Catalyzed
Reductive Coupling of Ynoates and Aldehydes
Sanjeewa K. Rodrigo, and Hairong Guan
J. Org. Chem., Just Accepted Manuscript • Publication Date (Web): 01 May 2017
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A Mechanistic Study of Nickel-Catalyzed Reductive Coupling of
Ynoates and Aldehydes
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Sanjeewa K. Rodrigo and Hairong Guan*
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Department of Chemistry, University of Cincinnati, Cincinnati, Ohio 45221ꢀ0172, United
States
ABSTRACT
In
this
work,
(1,5ꢀhexadiene)Ni(SIPr)
is used
(SIPr
=
1,3ꢀbis(2,6ꢀ
place of
diisopropylphenyl)imidazolidinꢀ2ꢀylidene)
in
Ni(COD)2/SIPr•HBF4/KOtBu (COD = 1,5ꢀcyclooctadiene) as a more robust catalyst for
regioselective reductive coupling of ynoates and aldehydes with triethylsilane. The
catalytic reaction of ethyl 3ꢀ(trimethylsilyl)propiolate and methyl 4ꢀformylbenzoate
shows firstꢀorder dependence on aldehyde and catalyst concentrations, inverse firstꢀorder
dependence on [ynoate], and no dependence on [silane]. The kinetics data, coupled with
deuteriumꢀlabeling experiments, support a mechanism involving dissociation of the
ynoate from a catalytically dormant nickelacyclopentadiene intermediate prior to
turnoverꢀlimiting formation of a catalytically active nickeladihydrofuran.
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INTRODUCTION
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Reductive coupling of alkynes and aldehydes has proven to be an efficient and
versatile method for the synthesis of allylic alcohols and their derivatives.1ꢀ10 Nickelꢀ
based catalytic systems in particular are notable for achieving high regioselectivity in
both intermolecular11ꢀ28 and intramolecular29ꢀ31 reductive couplings including selective
macrocyclization of ynals.23,32,33 Asymmetric variants of these reactions have also been
successfully developed using chiral phosphine or Nꢀheterocyclic carbene (NHC)
ligands.12ꢀ14,23,25 High tunability of the supporting ligand combined with a wide variety of
choices for the reductant allows a complete reversal of alkyne orientation through altering
steric interactions, thus offering opportunities for regiodivergent synthesis.34 The general
consensus is that these reactions proceed via turnoverꢀlimiting formation of
nickeladihydrofuran intermediates (Scheme 1), although using a bulky NHC ligand and a
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t
bulky reductant (e.g., Bu2MeSiH) can change the turnoverꢀlimiting step to the
subsequent σꢀbond metathesis with the reductant.35 The mechanistic details and nuances
have been fully elucidated by DFT calculations36ꢀ40 and the nickeladihydrofurans have
been characterized spectroscopically and crystallographically.41,42 The complexity of
these catalytic systems and the low stability of the nickel species, however, present
daunting challenges for kinetic analysis of the reactions. Nevertheless, Baxter and
Montgomery have investigated the kinetics of intramolecular reductive coupling of an
ynal with Et3SiH catalyzed by Ni(COD)2ꢀPCy3 (COD = 1,5ꢀcyclooctadiene, Cy =
cyclohexyl).43 Consistent with the hypothesis that the nickeladihydrofuran formation is
turnover limiting, the overall reaction is first order in both ynal and catalyst
concentrations but independent of the concentration of Et3SiH. Studying intramolecular
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coupling of alkyne and aldehyde built within one molecule, however, does not provide
information on the sequence of activating πꢀbonds at the nickel center. In addition,
kinetics of Ni(COD)2ꢀNHC catalyzed reductive coupling of alkynes and aldehydes have
not been studied in detail, so it is unclear if the kinetic features observed in the phosphine
case are reproduced in the NHC systems.
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SCHEME 1. Proposed Mechanism for Nickel-Catalyzed Reductive Coupling of
Alkynes and Aldehydes
We have been interested in using reductive coupling of ynoates and aldehydes to
make molecules with 1,4ꢀdifunctionalities (eq 1).44 The selectivity favors the ester group
(CO2R1) being placed distal to the newly formed C–C bond, as long as R1 is not
sufficiently bulky (e.g., R1 = Me, Et, and 2ꢀnaphthyl). To gain a deeper understanding of
the mechanism, we have conducted a kinetics study of the reaction. As illustrated in this
paper, for the NHC system, nickeladihydrofuran formation is also the turnoverꢀlimiting
step. Our results provide additional mechanistic insight, particularly the involvement of
an offꢀcycle species.
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R2
O
Ni(COD)2 (10 mol%)
R3
SIPr HBF4 (10 mol%) R1O
O
KOtBu
PPh3
(10 mol%)
(10 mol%)
H
OSiEt3
major product
R1O
R3CH2O
(1)
R2
THF, 23 oC
iPr
R2
O
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Et3SiH
iPr
R1O
H
N
N
R3
OSiEt3
iPr
iPr
minor product
SIPr
RESULTS AND DISCUSSION
For the reductive coupling of ynoates and aldehydes (eq 1), the ynoate substrate is
typically added slowly via a syringe pump to the mixture containing the rest of the
reagents to prevent nickelꢀcatalyzed trimerization of alkynes.45 This inevitably
complicates the kinetics study. Fortunately, ethyl 3ꢀ(trimethylsilyl)propiolate (1) was
identified as a substrate that reacts with aldehydes at rates much faster than the
trimerization process so that syringeꢀpump addition is not needed. The progress of the
reductive coupling reaction can thus be conveniently monitored by inꢀsitu IR
spectroscopy. To avoid band overlap between the starting materials and the products,
methyl 4ꢀformylbenzoate (2) was selected as the coupling aldehyde.46
The initial kinetics study was carried out using a catalytic mixture comprised of
Ni(COD)2, SIPr•HBF4 and KOtBu (10 mol% each).47 After several runs, it became
obvious that the data collected using the inꢀsitu generated catalyst were irreproducible.
This could be attributed to variable degree of catalyst decomposition. Ni(COD)2ꢀNHC
catalyzed reductive coupling reactions usually require a catalyst loading of 10 mol% or
even higher,32,33 indicating high sensitivity or low stability of the catalyst. Because the
catalyst is made from three components, we suspect that weighing errors might also
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contribute to the irreproducibility. In searching for a more robust nickel preꢀcatalyst,
Hazari’s (1,5ꢀhexadiene)Ni(SIPr) caught our attention as it was shown to be stable in
refluxing toluene48 and a superior substitute for Ni(COD)2 in nickelꢀcatalyzed reactions.49
To ensure this particular nickel complex catalyzes the reductive coupling process, the
reaction of methyl propiolate and benzaldehyde with triethylsilane was examined first
(Table 1). Comparing to the inꢀsitu generated catalyst, (1,5ꢀhexadiene)Ni(SIPr) appears
to live longer, requiring a lower amount of catalyst (5 mol%) to achieve high yield.
However, reducing the catalyst loading further or having a more dilute solution results in
significant erosion in yield. In any case, the observed regioselectivity (3 : 4 = 90 : 10) is
comparable to the one obtained from the reaction catalyzed by
Ni(COD)2/SIPr•HBF4/KOtBu (3 : 4 = 85 : 15).44
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TABLE 1. Reductive Coupling of Methyl Propiolate and Benzaldehyde Catalyzed
by (1,5-hexadiene)Ni(SIPr)a
entry catalyst loading (mol %) [Ni catalyst] (M) yield (%)b
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0.020
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0.0025
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2.5
aMethyl propiolate was added to the reaction mixture over a period of 8 h using a syringe
pump, after which the reaction was stirred for another 1 h. bCombined GC yield for 3
and 4 (90 : 10).
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The preꢀsynthesized nickel complex (1,5ꢀhexadiene)Ni(SIPr) was then tested for
catalytic reductive coupling of 1 and 2, which were the substrates chosen for the kinetics
study (eq 2). The reaction is highly regioselective, producing 5 exclusively. In this
specific case, the catalyst concentration could be kept relatively low ([Ni] = 0.0050 M)
without compromising the product yield. These results suggested that using (1,5ꢀ
hexadiene)Ni(SIPr) would address the stability issues associated with the inꢀsitu
generated catalyst.
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To measure the kinetics for the reaction shown in eq 2, the disappearance of 1 was
monitored by inꢀsitu IR spectroscopy and the absorbance values were converted to
concentrations using a calibration plot (see Supporting Information). Initial rates were
calculated based on data points acquired up to 30% conversion. The reaction order for
each reagent was determined by varying their initial concentrations (Figure 1).
Interestingly, the overall reaction is inversely proportional to the concentration of the
ynoate, suggesting the presence of an offꢀcycle species from which 1 can reversibly
dissociate. The reductive coupling process shows firstꢀorder dependence on both
aldehyde and catalyst concentrations but zerothꢀorder dependence on [Et3SiH], implying
that the interaction with Et3SiH occurs after the turnoverꢀlimiting step. It should be
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mentioned that the initial rates show a slight nonꢀlinear dependence on catalyst loading at
a low catalyst concentration (0.0050 M, Figure 1, lower left plot). This is likely due to
irreversible catalyst deactivation in a dilute solution (Table 1).
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[Et3SiH] (M)
[Ni catalyst] (M)
Figure 1. Initial rates as functions of [1], [2], [Ni catalyst] and [Et3SiH]. Each data point
is the average of three runs and the error bar represents the standard deviation of the three
runs.
To discern whether or not the reaction features oxidative addition of Et3SiH, the
reductive coupling reaction was performed in the presence of a 1 : 1 mixture of Et3SiH
and Et3SiD (eq 3). Analyzing the protio content of the product reveals a 1 : 1 mixture of
5 and 5-D. Similar results have been previously observed for nickelꢀcatalyzed
intramolecular reductive coupling of an ynal43 and rhodiumꢀcatalyzed hydrosilylation of
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acetophenone with PhMe2SiH.50,51 This type of intermolecular competition experiment
can be used to differentiate a mechanism involving direct E–H bond cleavage from the
one involving substrate binding followed by E–H bond cleavage.52 The lack of kinetic
isotope effect observed here supports the latter scenario.
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A mechanism consistent with the kinetics results is outlined in Scheme 2. We
propose that nickelacyclopentadiene A is in an equilibrium53 with complex B and 1 while
the subsequent insertion of aldehyde 2 or the formation of nickeladihydrofuran C is the
turnoverꢀlimiting step. The rate law for the overall catalytic process is thus given in eq 4
with the assumption that the equilibrium is fully established and favors A (or [1] >> Keq).
Under this mechanistic scenario, increasing the initial concentration of 1 would shift the
equilibrium more towards the dormant species A, resulting in a slower catalytic reaction.
The silane participates in catalyst regeneration after the turnoverꢀlimiting step; therefore,
changing its concentration does not impact the rate for the overall reaction. To account
for the lack of kinetic isotope effect from silane, we propose intermediate D in which the
Si–H bond is not yet broken. Related intermediates have been suggested in DFT
calculations on the cleavage of Ni–O bonds by boranes.54
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SCHEME 2. Proposed Catalytic Cycle for Nickel-Catalyzed Reductive Coupling of
Ynoates and Aldehydes
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Unfortunately, our attempts to synthesize A independently were unsuccessful (see
Supporting Information). Nickelacyclopentadienes have been previously proposed as
intermediates in nickelꢀcatalyzed cycloaddition reactions,55 although wellꢀcharacterized
ones often involve coordination of the nickelacyclopentadiene ring to another metal.56ꢀ59
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Reductive coupling of ynoates or their derivatives to form metallocyclopentadienes is,
however, precedented with palladium60ꢀ63 and iridium.64 Envisioning severe steric
repulsions between the Me3Si groups and the iPr groups of SIPr, we tentatively place the
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Me3Si groups at the
β positions of the nickelacyclopentadiene. This regioisomer is also
electronically favored by placing the electronꢀwithdrawing ester groups at the α
positions.65 We cannot however rule out the possibility that A exists as a bis(alkyne)
complex.66 Our results are consistent with DFT calculations of related reactions showing
that the alkyne substrate is activated first at the nickel center.37,40
Whittaker and Dong have recently proposed oxidative addition of an aldehyde C–
H bond to an NHCꢀligated Ni(0) species.67 According to DFT calculations,68 such a
process is promoted by the binding of another substrate with πꢀaccepting ability, which in
this case could be the ynoate. If this mechanism were operative (Scheme 3), insertion of
ynoate into the resulting Ni–H bond and then reductive elimination of 6 followed by
rapid nickelꢀcatalyzed hydrosilylation of 6 would also agree with our kinetics results.
However, this mechanism contradicts our deuteriumꢀlabeling experiments (Scheme 4).
Deuterium originated from the silane is located at the αꢀcarbon to the ester group
whereas deuterium originated from the aldehyde remains attached to its original carbon.
In addition, our control experiments show that at room temperature Ni(COD)2ꢀSIPr does
not catalyze the hydrosilylation of ynoate or aldehydes.69,70 On the other hand, the
deuteriumꢀlabeling experiments are consistent with the nickeladihydrofuran mechanism
shown in Scheme 2.
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SCHEME 3. An Alternative Mechanism Featuring C–H Bond Activation
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SCHEME 4. Deuterium-Labeling Experiments
CONCLUSION
In summary, we have identified a relatively stable Ni(0)ꢀNHC complex for
catalytic reductive coupling of ynoates and aldehydes, which gives more reliable kinetics
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data than using the catalyst generated inꢀsitu from Ni(COD)2, an imidazolinium, and
KOtBu. Our mechanistic study suggests that the ynoate reacts with nickel to produce a
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catalytically dormant nickelacyclopentadiene outside of the catalytic cycle.
Its
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dissociation of ynoate to form a nickelacyclopropene or an η2ꢀynoate complex allows the
aldehyde molecule to interact with nickel to generate a nickeladihydrofuran. The
turnoverꢀlimiting and regioselectivityꢀdetermining step of the reductive coupling process
is the formation of the nickeladihydrofuran. The discovery of the offꢀcycle species, a
nickelacyclopentadiene, is important for future development of nickelꢀcatalyzed
reductive coupling reactions. As demonstrated in other catalytic processes,71ꢀ73
deconvolution of productive and nonꢀproductive pathways can lead to the improvement
of the catalytic efficiency. Our ongoing efforts focus on modification of the reaction
protocol and identification of ynoates that are unlikely to form the offꢀcycle species.
EXPERIMENTAL SECTION
General Experimental Methods. Unless otherwise mentioned, all airꢀsensitive
compounds were handled under an inert atmosphere using standard Schlenk line and
inertꢀatmosphere box techniques. THF was deoxygenated and dried in a solvent
purification system by passing through an activated alumina column and an oxygenꢀ
scavenging column under argon. Substrates used in this study were purchased from
commercial sources (1 from Acros Organics; 2 and Et3SiH from Aldrich) and used
without further purification. (1,5ꢀhexadiene)Ni(SIPr) was synthesized according to
literature procedures.48
Inꢀsitu FTꢀIR data were acquired using a Remspec
ReactionView Mid IR Fiberꢀoptic System equipped with an ATR probe. Highꢀ
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resolution mass spectrometry (HRMS) data were acquired using a Micromass QꢀTOFꢀ
2TM (hybrid quadrupole timeꢀofꢀflight) mass spectrometer.
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Reductive Coupling of 1 and 2 Catalyzed by (1,5-hexadiene)Ni(SIPr). In a
flameꢀdried Schlenk flask, (1,5ꢀhexadiene)Ni(SIPr) (13.3 mg, 0.025 mmol) was dissolved
in 4 mL of THF, resulting in an orange solution. In a separate flameꢀdried Schlenk flask,
1 (95 µL, 0.50 mmol), 2 (82 mg, 0.50 mmol) and Et3SiH (80 µL, 0.50 mmol) were mixed
with 1 mL of THF. This mixture was then added to the orange catalyst solution in one
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o
portion using a syringe. The resulting mixture was stirred at room temperature (23 C)
until the starting materials were fully consumed (~ 5 h as monitored by TLC). The
volatiles were removed under vacuum and the crude product was purified by column
chromatography (eluted by diethyl ether/hexanes) to yield 5 (218 mg, 97% yield) as a
1
colorless oil. H NMR (400 MHz, CDCl3, δ) 7.98 (d, J = 8.0 Hz, 2H), 7.34 (d, J = 8.0
Hz, 2H), 6.83 (s, 1H), 5.42 (s, 1H), 4.21 (q, J = 6.8 Hz, 2H), 3.89 (s, 3H), 1.32 (t, J = 6.8
13
Hz, 3H), 0.90 (t, J = 8.0 Hz, 9H), 0.59 (q, J = 8.0 Hz, 6H), 0.00 (s, 9H); C{1H} NMR
(101 MHz, CDCl3, δ) 167.2, 167.0, 164.1, 147.1, 130.4, 129.6, 129.4, 127.6, 78.4, 60.5,
52.2, 14.4, 6.9, 5.0, 0.1; IR (neat, cmꢀ1) 2953, 2877, 1720, 1610, 1458, 1435, 1411, 1369,
1305, 1276, 1244, 1186, 1083, 1037, 1005, 971, 905, 838, 811, 728, 707, 617, 579, 536,
495; HRMS (ESI) m/z: [M + Na]+ Calcd for C23H38O5Si2Na 473.2155; Found 473.2154.
General Procedures for Determining the Initial Rates Using in-situ IR
o
Spectroscopy. At room temperature (23 C) under an argon atmosphere, (1,5ꢀ
hexadiene)Ni(SIPr) (13.3 mg, 0.025 mmol) was dissolved in 4 mL of THF in a 10 mL
scintillation vial capped by a Teflon septum. The IR probe of ReactionView was
inserted into a 25 mL threeꢀnecked flask through its center neck under a positive argon
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flow. The flask with the probe was immersed in a constant temperature bath set to 25 oC.
The catalyst mixture was transferred into the flask via a cannula and allowed to
equilibrate for at least 15 min. Solvent subtracted spectra were recorded at 60ꢀsecond
intervals until the baseline of the IR spectrum and the temperature of the solution had
stabilized (~15 min). A mixture of 1 (95 ꢁL, 0.50 mmol), 2 (82 mg, 0.50 mmol) and
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Et3SiH (80 ꢁL, 0.50 mmol) in 1 mL of THF (preꢀmixed in another 10 mL scintillation
vial capped by a Teflon septum) was added to the catalyst solution all at once via a thin
cannula. The progress of the reaction was monitored by observing the absorbance of the
ynoate C–O stretch (1233 cmꢀ1) as a function of time. Absolute absorbance values were
obtained by comparing the band at 1233 cmꢀ1 to the baseline at 1345 cmꢀ1. The
absorbance values were converted to concentration values using a calibration plot. The
reaction was monitored up to 30% conversion to reflect the catalytic rates for several
turnovers.
ASSOCIATED CONTENT
Supporting Information
Experimental details, characterization data for 5 and kinetics data. This material is
available free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
Eꢀmail: hairong.guan@uc.edu
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Notes
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The authors declare no competing financial interest.
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ACKNOWLEDGMENTS
We thank the National Science Foundation (CHEꢀ0952083 and CHEꢀ1464734) for
support of this research.
REFERENCES
(1) Montgomery, J. Acc. Chem. Res. 2000, 33, 467ꢀ473.
(2) Ikeda, S. Angew. Chem. Int. Ed. 2003, 42, 5120ꢀ5122.
(3) Montgomery, J. Angew. Chem. Int. Ed. 2004, 43, 3890ꢀ3908.
(4) Jang, H.ꢀY.; Krische, M. J. Acc. Chem. Res. 2004, 37, 653ꢀ661.
(5) Skucas, E.; Ngai, M.ꢀY.; Komanduri, V.; Krische, M. J. Acc. Chem. Res. 2007, 40,
1394ꢀ1401.
(6) Moslin, R. M.; MillerꢀMoslin, K.; Jamison, T. F. Chem. Commun. 2007, 4441ꢀ
4449.
(7) Montgomery, J.; Sormunen, G. J. Top. Curr. Chem. 2007, 279, 1ꢀ23.
(8) Bower, J. F.; Kim, I. S.; Patman, R. L.; Krische, M. J. Angew. Chem. Int. Ed. 2009,
48, 34ꢀ46.
(9) Reichard, H. A.; McLaughlin, M.; Chen, M. Z.; Micalizio, G. C. Eur. J. Org. Chem.
2010, 391ꢀ409.
(10) Tanaka, K.; Tajima, Y. Eur. J. Org. Chem. 2012, 3715ꢀ3725.
(11) Huang, W.ꢀS.; Chan, J.; Jamison, T. F. Org. Lett. 2000, 2, 4221ꢀ4223.
(12) Miller, K. M.; Huang, W.ꢀS.; Jamison, T. F. J. Am. Chem. Soc. 2003, 125, 3442ꢀ
3443.
(13) Miller, K. M.; Molinaro, C.; Jamison, T. F. Tetrahedron: Asymmetry 2003, 14,
3619ꢀ3625.
(14) Colby, E. A.; Jamison, T. F. J. Org. Chem. 2003, 68, 156ꢀ166.
(15) Takai, K.; Sakamoto, S.; Isshiki, T. Org. Lett. 2003, 5, 653ꢀ655.
(16) Mahandru, G. M.; Liu, G.; Montgomery, J. J. Am. Chem. Soc. 2004, 126, 3698ꢀ
3699.
(17) Miller, K. M.; Luanphaisarnnont, T.; Molinaro, C.; Jamison, T. F. J. Am. Chem. Soc.
2004, 126, 4130ꢀ4131.
(18) Miller, K. M.; Jamison, T. F. J. Am. Chem. Soc. 2004, 126, 15342ꢀ15343.
(19) Moslin, R. M.; Jamison, T. F. Org. Lett. 2006, 8, 455ꢀ458.
(20) Takai, K.; Sakamoto, S.; Isshiki, T.; Kokumai, T. Tetrahedron 2006, 62, 7534ꢀ7539.
(21) Moslin, R. M.; Miller, K. M.; Jamison, T. F. Tetrahedron 2006, 62, 7598ꢀ7610.
(22) Saꢀei, K.; Montgomery, J. Org. Lett. 2006, 8, 4441ꢀ4443.
15
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Page 16 of 18
1
2
3
4
5
(23) Chaulagain, M. R.; Sormunen, G. J.; Montgomery, J. J. Am. Chem. Soc. 2007, 129,
9568ꢀ9569.
(24) Baxter, R. D.; Montgomery, J. J. Am. Chem. Soc. 2008, 130, 9662ꢀ9663.
(25) Yang, Y.; Zhu, S.ꢀF.; Zhou, C.ꢀY.; Zhou, Q.ꢀL. J. Am. Chem. Soc. 2008, 130,
14052ꢀ14053.
(26) Saito, N.; Katayama, T.; Sato, Y. Org. Lett. 2008, 10, 3829ꢀ3832.
(27) Malik, H. A.; Chaulagain, M. R.; Montgomery, J. Org. Lett. 2009, 11, 5734ꢀ5737.
(28) Malik, H. A.; Sormunen, G. J.; Montgomery, J. J. Am. Chem. Soc. 2010, 132, 6304ꢀ
6305.
(29) Oblinger, E.; Montgomery, J. J. Am. Chem. Soc. 1997, 119, 9065ꢀ9066.
(30) Tang, X.ꢀQ.; Montgomery, J. J. Am. Chem. Soc. 1999, 121, 6098ꢀ6099.
(31) Saito, N.; Sugimura, Y.; Sato, Y. Org. Lett. 2010, 12, 3494ꢀ3497.
(32) Shareef, A.ꢀR.; Sherman, D. H.; Montgomery, J. Chem. Sci. 2012, 3, 892ꢀ895.
(33) Wang, H.; Negretti, S.; Knauff, A. R.; Montgomery, J. Org. Lett. 2015, 17, 1493ꢀ
1496.
(34) Jackson, E. P.; Malik, H. A.; Sormunen, G. J.; Baxter, R. D.; Liu, P.; Wang, H.;
Shareef, A.ꢀR.; Montgomery, J. Acc. Chem. Res. 2015, 48, 1736ꢀ1745.
(35) Jackson, E. P.; Montgomery, J. J. Am. Chem. Soc. 2015, 137, 958ꢀ963.
(36) McCarren, P. R.; Liu, P.; Cheong, P. H.ꢀY.; Jamison, T. F.; Houk, K. N. J. Am.
Chem. Soc. 2009, 131, 6654ꢀ6655.
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(37) Liu, P.; McCarren, P.; Cheong, P. H.ꢀY.; Jamison, T. F.; Houk, K. N. J. Am. Chem.
Soc. 2010, 132, 2050ꢀ2057.
(38) Liu, P.; Montgomery, J.; Houk, K. N. J. Am. Chem. Soc. 2011, 133, 6956ꢀ6959.
(39) Haynes, M. T., II, Liu, P.; Baxter, R. D.; Nett, A. J.; Houk, K. N.; Montgomery, J. J.
Am. Chem. Soc. 2014, 136, 17495ꢀ17504.
(40) Liu, T.; Bi, S. Organometallics 2016, 35, 1114ꢀ1124.
(41) Ogoshi, S.; Arai, T.; Ohashi, M.; Kurosawa, H. Chem. Commun. 2008, 1347ꢀ1349.
(42) Ohashi, M.; Saijo, H.; Arai, T.; Ogoshi, S. Organometallics 2010, 29, 6534ꢀ6540.
(43) Baxter, R. D.; Montgomery, J. J. Am. Chem. Soc. 2011, 133, 5728ꢀ5731.
(44) Rodrigo, S. K.; Guan, H. J. Org. Chem. 2012, 77, 8303ꢀ8309.
(45) Rodrigo, S. K.; Powell, I. V.; Coleman, M. G.; Krause, J. A.; Guan, H. Org.
Biomol. Chem. 2013, 11, 7653ꢀ7657.
(46) The following aldehydes were deemed to be unsuitable for the kinetics study due to
significant overlap of IR bands: PhCHO, oꢀXC6H4CHO (X = Me, Cl, F), pꢀ
XC6H4CHO (Me, MeO, tBu), (CH3)2CHCH2CHO and CH3(CH2)5CHO.
(47) In our methodology study,44 PPh3 was added to enhance the stability of the catalyst.
To simplify the kinetics study and to focus on NHC ligand system only, we decided
to remove PPh3 from the catalytic mixture. The removal of PPh3 decreases the
yield (from 100% to 61%) but does not impact on the selectivity.
(48) Wu, J.; Faller, J. W.; Hazari, N.; Schmeier, T. J. Organometallics 2012, 31, 806ꢀ
809.
(49) Nett, A. J.; Zhao, W.; Zimmerman, P. M.; Montgomery, J. J. Am. Chem. Soc. 2015,
137, 7636ꢀ7639.
(50) Zheng, G. Z.; Chan, T. H. Organometallics 1995, 14, 70ꢀ79.
(51) Schneider, N.; Finger, M.; Haferkemper, C.; BelleminꢀLaponnaz, S.; Hofmann, P.;
Gade, L. H. Chem. Eur. J. 2009, 15, 11515ꢀ11529.
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2
3
4
5
6
7
8
9
(52) Simmons, E. M.; Hartwig, J. F. Angew. Chem. Int. Ed. 2012, 51, 3066ꢀ3072.
(53) For an example of a nickelacyclopropene reacting with an alkyne to give a
nickelacyclopentadiene, see: Müller, C.; Lachicotte, R. J.; Jones, W. D.
Organometallics 2002, 21, 1975ꢀ1981.
(54) Huang, F.; Zhang, C.; Jiang, J.; Wang, Z.ꢀX.; Guan, H. Inorg. Chem. 2011, 50,
3816ꢀ3825.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
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35
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37
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41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(55) Zargarian, D. NickelꢀCarbon πꢀBonded Complexes. In Comprehensive
Organometallic Chemistry III; Crabtree, R. H., Mingos, D. M. P., Eds.; Elsevier:
Amsterdam, 2007; Vol. 8, pp 133ꢀ196.
(56) Colbran, S. B.; Robinson, B. H.; Simpson, J. Organometallics 1985, 4, 1594ꢀ1601.
(57) Zeng, Y.; Feng, H.; King, R. B.; Schaefer, H. F., III Organometallics 2014, 33,
4410ꢀ4416.
(58) Altenburger, K.; Arndt, P.; Spannenberg, A.; Rosenthal, U. Eur. J. Inorg. Chem.
2015, 44ꢀ48.
(59) Wei, J.; Zhang, W.ꢀX.; Xi, Z. Angew. Chem. Int. Ed. 2015, 54, 5999ꢀ6002.
(60) Hauwert, P.; Boerleider, R.; Warsink, S.; Weigand, J. J.; Elsevier, C. J. J. Am.
Chem. Soc. 2010, 132, 16900ꢀ16910.
(61) Nägele, P.; Herrlich, U.; Rominger, F.; Hofmann, P. Organometallics 2013, 32,
181ꢀ191.
(62) Canovese, L.; Santo, C.; Scattolin, T.; Visentin, F.; Bertolasi, V. J. Organomet.
Chem. 2015, 794, 288ꢀ300.
(63) Canovese, L.; Visentin, F.; Scattolin, T.; Santo, C.; Bertolasi, V. Dalton Trans.
2015, 44, 15049ꢀ15058.
(64) Paneque, M.; Posadas, C. M.; Poveda, M. L.; Rendón, N.; Álvarez, E.; Mereiter, K.
Chem. Eur. J. 2007, 13, 5160ꢀ5172.
(65) Komagawa, S.; Wang, C.; Morokuma, K.; Saito, S.; Uchiyama, M. J. Am. Chem.
Soc. 2013, 135, 14508ꢀ14511.
(66) Rosenthal, U.; Pulst, S.; Kempe, R.; Pörschke, K.ꢀR.; Goddard, R.; Proft, B.
Tetrahedron 1998, 54, 1277ꢀ1287.
(67) Whittaker, A. M.; Dong, V. M. Angew. Chem. Int. Ed. 2015, 54, 1312ꢀ1315.
(68) Yu, H.; Fu, Y. Chem. Eur. J. 2012, 18, 16765ꢀ16773.
o
(69) At 50 C, Ni(COD)2ꢀSIPr can catalyze the hydrosilylation of PhCHO to yield
Et3SiOCH2Ph.
(70) Hydrosilylation of alkynes without ester groups can be catalyzed by Ni(COD)2ꢀ
NHC. For details, see: Chaulagain, M. R.; Mahandru, G. M.; Montgomery, J.
Tetrahedron 2006, 62, 7560ꢀ7566.
(71) Hein, J. E.; Armstrong, A.; Blackmond, D. G. Org. Lett. 2011, 13, 4300ꢀ4303.
(72) Baxter, R. D.; Sale, D.; Engle, K. M.; Yu, J.ꢀQ.; Blackmond, D. G. J. Am. Chem.
Soc. 2012, 134, 4600ꢀ4606.
(73) Brezny, A. C.; Landis, C. R. J. Am. Chem. Soc. 2017, 139, 2778ꢀ2785.
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Table of Contents/Abstract Graphic
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5 mol%
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SiMe3
Ar
Ni SIPr
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EtO2C
EtO2C
SiMe3
THF, 23 oC
Et3SiH ArCHO
H
OSiEt3
H
k[Ni][aldehyde]
Vcat
=
[ynoate]
EtO2C
EtO2C
Z
Z
SiMe3
SiMe3
Z
Z
SiMe3
Ar
Ni
Ni
O
EtO2C
dormant
active
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