Comparison of imine to olefin insertion reactions: Generation of five- and six-membered lactams via a nickel-mediated co, olefin, co, imine insertion cascade

Article abstract of DOI:10.1021/om1011566

Cationic nickel complexes of the form L₂Ni(CH ₃)(RN=C(H)R)⁺ (L₂ = bidentate nitrogen donor) have been probed for their ability to mediate olefin and imine migratory insertion reactions. While these complexes do

Full text of DOI:10.1021/om1011566

ARTICLE
pubs.acs.org/Organometallics
Comparison of Imine to Olefin Insertion Reactions: Generation of Five-
and Six-Membered Lactams via a Nickel-Mediated CO, Olefin, CO,
Imine Insertion Cascade
Jason L. Davis and Bruce A. Arndtsen*
Department of Chemistry, McGill University, 801 Sherbrooke Street West, Montreal, Quꢀebec H3A 2K6, Canada
S Supporting Information
b
ABSTRACT: Cationic nickel complexes of the form L2Ni-
(CH3)(RNdC(H)R)þ (L2 = bidentate nitrogen donor) have
been probed for their ability to mediate olefin and imine
migratory insertion reactions. While these complexes do not
undergo alkene insertion into the nickel-methyl bond, the use
of olefin-tethered imines CH2dCH(CH2)nNdC(R)aryl (n =
1-3; R = H, methyl, phenyl) and the addition of CO initiates
competitive olefin and imine insertion into the in situ generated
nickel-acyl complex. The insertion selectivity shows clear
steric and electronic influences and suggests that strong imine
coordination can allow it to compete with the more rapid
insertion of alkenes. This reactivity has been employed to develop a CO/alkene/CO/imine insertion cascade to synthesize five- and
six-membered-ring lactams.
Scheme 1. Sequential Insertion of CO and Imine into Nickel-
ransition-metal-mediated carbon-carbon and carbon-
Alkyl Bonds
T
nitrogen bond forming reactions have become important
fundamental reactions in synthetic chemistry. While many
variants of these reactions exist, those that incorporate unsatu-
rated molecules via their migratory insertion into metal-ligand
bonds have seen extensive use, especially with alkenes as
substrates (e.g., alkene hydrogenation,1 hydroformylation,2 Heck
couplings,3 olefin polymerization,4 and related reactions). How-
ever, analogous transformations employing heteroatom-contain-
ing unsaturated substrates such as imines and aldehydes are less
common, despite their structural similarity. Perhaps the most
established of these are catalytic hydrogenation or related
reductions.5 More recently, the metal-catalyzed addition of
organometallic reagents to imines and aldehydes has also been
achieved.6
those of CO/alkene insertion. For example, imines readily
undergo insertion into the in situ generated nickel-acyl bond
of 2 to form metal-chelated amides (Scheme 1).8 The generation
of a strong amide bond is believed to provide the driving force for
these reactions. Considering that these same nickel complexes
have been demonstrated to readily undergo alkene insertion
reactions,13 this system provides an intriguing opportunity to
probe the relative insertion propensity of these two distinct units.
To our knowledge, this fundamental comparison of imine and
olefin insertion has not been previously explored and could be
important in the development of synthetic processes that utilize
both alkenes and imines as insertion substrates. We report below
the results of these efforts, which examine the steric, electronic,
and regiochemical effects governing competitive insertion be-
tween R-olefins and imines. This reactivity has been used to
The extensive use of alkene insertion reactions in synthetic
processes suggests that the analogous reaction with imines could
provide an effective method for generating carbon-nitrogen
bonds. However, until only recently, examples of even the
stoichiometric insertion of imines into late-metal-carbon bonds
in a fashion analogous to that for alkenes were rare.7-11 This has
been postulated to be at least partially based upon thermody-
namics, where the insertion of an imine into a metal-carbon
bond to cleave a carbon-nitrogen π bond and form a new
carbon-nitrogen σ bond is not expected to be nearly as
exothermic as is observed with alkene insertion.7,12
Both ourselves7,8 and others9-11 have demonstrated that CO
and imines can undergo sequential migratory insertion into late-
transition-metal-carbon bonds to yield products analogous to
Received: December 8, 2010
Published: March 15, 2011
r
2011 American Chemical Society
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design a nickel-mediated, four-component insertion cascade to
construct five- and six-membered lactams.
Scheme 2. Selective Insertion of CO and Imine into Nickel-
Methyl Bonds in the Presence of Styrene
’ RESULTS AND DISCUSSION
We have previously demonstrated that imines bound to cationic
nickel complexes of the form 1 (Scheme 1; BArf = B(3,5-
C6H3(CF3)2)4, p-Tol = p-C6H4CH3) do not undergo insertion
into the nickel-methyl bond, even at elevated temperature.8
However, exposure of these complexes to 1 atm of carbon
monoxide leads to the formation of the analogous Ni-acyl
complex 2, which can undergo imine migratory insertion into
the Ni-COCH3 bond to generate the stable metallacycle 3. The
kinetic barrier to this imine insertion (ΔGq = 23 kcal/mol at
40 °C) is significantly higher than that previously reported for
alkene insertions into analogous nickel-carbon bonds (e.g., ΔGq
= 14 kcal/mol at -40 °C for styrene).13,14 This rate difference, as
well as the prerequisite CO insertion, led us to question the
ability of imines to undergo competitive insertion in the presence
of olefins. However, migratory insertion is considered to be an
intramolecular reaction from the coordinated unsaturated sub-
strate, and the basicity of the imine nitrogen should compete
favorably with olefins for binding to the nickel center.
As an initial probe of this competition, 2 equiv of styrene was
added to the nickel-imine complex 1 (Scheme 1). While the
analogous non-imine-coordinated Ni-alkyl complexes are known
to mediate the insertion of R-olefins very rapidly at ambient
temperature,15 complex 1 does not react with styrene after several
days, and no evidence is observed for decomposition of complex 1
or olefin consumption. This lack of reactivity, and no visible signal
broadening in the 1H NMR spectrum, suggested that imine remains
bound to the metal center during the reaction, effectively blocking
olefin coordination for insertion. This is notable, since previous
studies have determined that the imines in these nickel complexes
are relatively labile and could be rapidly replaced by other nitrogen
donors (e.g., other imines or CH3CN).8
introducing a tethered R-olefin into the system, which may
potentiallly undergo associative ligand substitution more readily
than a free alkene, might allow for competitive insertion with imines.
The alkene-tethered imine complex can be prepared by the addition
of the iminium salt 5a to (bipy)Ni(CH3)2 (4; bipy = 2,20-bipyridyl)
in CH2Cl2, which affords the deep red cationic complex 6a, along
with the rapid liberation of methane (eq 1). No evidence for olefin
coordination or insertion was observed in 6a, and the 1H and 13
C
NMR spectra display a single nickel-methyl signal (1H NMR
(CD2Cl2) δ 0.09 (s, 3H, Ni-CH3)]), as well as downfield shifts in
the imine resonances (1H NMR δ 8.40 (s, dC(H)-p-Tol), 13C
NMR δ 169.1 (s, dC(H)-p-Tol); free imine, 1H NMR δ 8.27 (s, d
C(H)-p-Tol), 13C NMR δ 161.4 (s, dC(H)p-Tol)), consistent
with η1 binding of the imine through the nitrogen lone pair.7-9
These complexes are stable at room temperature in solution and can
be isolated as solids. They are thermally unstable, however, and
upon heating undergo complex decomposition, during which the
1H NMR signals associated with the olefin are consumed.
In an effort to initiate imine dissociation and subsequent
insertion, carbon monoxide was added to the reaction mixture.
This leads to the rapid insertion of carbon monoxide to form 2,
which subsequently converts to the imine insertion product 3
(Scheme 2), and no evidence for styrene insertion is observed.
The observation that a relatively bulky, trans-disubstituted imine
can undergo preferential insertion relative to an R-olefin into the
nickel-carbon bond is not consistent with their relative insertion
rates. However, it does correlate with the stronger binding of the
Lewis basic imine to the cationic nickel center. We rationalized that
Adding 1 atm of carbon monoxide to 6a in CD2Cl2 and
monitoring the reaction by H NMR shows the rapid, in situ
1
Scheme 3. Products of Competitive Insertion with Olefin-Tethered Imines
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Scheme 4. CO/Olefin/CO/Imine Insertion Cascade
Table 1. Steric and Electronic Effects on Competitive
Insertiona
formation of the Ni-acyl complex 7a (Scheme 3) within 5 min
(Ni(COCH3), δ 2.60 ppm).16 This CO insertion initiates the
competitive insertion of the olefin or imine unit into the newly
generated nickel-acyl bond. After 48 h, the product of imine
insertion (8a), as well as the bicyclic complex 10a (as a mixture of
diastereomers) are observed in a ca. 1:1 ratio.17 Nickel complex
10a represents the unusual product of the insertion cascade
illustrated in Scheme 4, where olefin insertion into the Ni-acyl
bond leads to the formation of a new Ni-alkyl bond, which can
undergo insertion of a second equivalent of CO, followed by
cyclization via imine insertion. Consistent with our previous
observations, the metal-chelated amides are inert to further
insertion reactions. The addition of a KCN/MeOH solution to
these complexes readily cleaves the organic fragments from the
metal center, affording the hydroacylated imine 9a and the
lactam 11a.
Carbon monoxide appears to play a critical role in this
reaction, as both an insertion monomer and an initiator for
imine and alkene insertion. As was previously demonstrated,
imine insertion requires the formation of a nickel-acyl ligand to
be more thermodynamically viable.8 The reason for alkene
insertion proceeding only after CO insertion is less clear, though
it may be due to the olefin being able to compete more favorably
with the imine for coordination to the Ni-acyl complex, perhaps
by CO behaving as a ligand to initiate an associative exchange
process between imine and the alkene. Alternatively, the steric
requirement of the nickel-acyl ligand may favor imine displace-
ment. While no evidence for alkene coordination is observed,
given the much faster rates of alkene insertion, even a small
equilibrium formation of 12 (Scheme 4) should allow for
competitive olefin insertion.
a (bipy)Ni(Me)2 (200 mg, 0.85 mmol) and iminium salt (0.85 mmol) in
20 mL of CH2Cl2, 1 atm of CO, for 48 h at room temperature.
b (L)NiMe2 complexes generated in situ from (tmeda)NiMe2.
Product selectivity also exhibits strong steric trends. Not
surprisingly, use of the more sterically encumbered trisubstituted
imines derived from acetophenone and benzophenone greatly
reduced its ability to compete for insertion with the alkene
(Table 1, entries g and h). Nevertheless, these imines undergo
intramolecular insertion at room temperature to form the lactam
in good yield. While β-hydride elimination is often the final step
in many insertion-based cascade reactions, these metallacycles
appear to be particularly resistant to further reaction, even upon
prolonged heating (eq 2).18 This is presumably due to the
restricted rotation induced by tight chelation to the amide
oxygen, which may prevent the β-hydrogens from adopting the
syn orientation required for elimination to occur.
On the basis of this analysis, it was rationalized that modifying
the ability of the imine to bind to the metal center should provide
some degree of control over the relative insertion propensity of
olefins and imines. For example, the use of electron-withdrawing
substituents on the imine reduces its ability to bind to the metal
center and favors cyclization by initial olefin insertion to form
product 11 (Table 1, entry b). Conversely, more electron rich
imines favor the formation of the imine insertion product 9
(Table 1, entry c). The ratio of products is also affected by the
ligands on the metal center, where increasing electron density on
the ligand (Table 1, entries d and e) favor lactam formation. The
latter may result from the more electron rich and more strongly
back-bonding nickel center favoring coordination to the alkene.
Use of the harder tetramethylethylenediamine ligand yields only
the product of imine insertion (Table 1, entry f).
Control over the relative rates of insertion provided an unusual
route to synthesize substituted lactams (11) via four separate
insertion steps (CO, olefin, CO, and imine). In an effort to further
probe the generality of this insertion cascade, longer tethers between
the imine and olefin were employed. When the tether length was
increased by one carbon, the six-membered lactam (13) was formed
in only 20% yield, with the major product being instead the five-
membered exo-cyclization product (14, 60%) (Scheme 5).
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Scheme 5. Synthesis of Five- and Six-Membered Lactams
coordinating ability of imines is a major factor in these reactions.
These effects can be used to direct the reaction toward either
imine hydroacylation or cyclization to form lactams. The latter
has been used to design a new, nickel-mediated one-pot insertion
cascade of CO, olefin, a second unit of CO, and imine, to
synthesize five- and six-membered lactams in good yield under
mild conditions. Further investigation into the relative insertion
propensity of imines with other types of unsaturated monomers,
as well as studies directed toward the coupling of these cycliza-
tions into catalytic reactions (e.g., cross-coupling), should further
expand the scope and utility of this chemistry.
’ EXPERIMENTAL SECTION
Extension of the tether to three methylene units provided the six-
membered lactam (15) with almost complete selectivity (72%
yield) and none (<5%) of the seven-membered lactam.
General Procedures. Unless otherwise noted, all manipulations
were carried out under an inert atmosphere in a drybox or using standard
Schlenk or vacuum line techniques. H and 13C NMR spectra were
1
The change in regioselectivity in the olefin insertion step
appears to be directly related to the length of the tether, though
the exact nature of the directing influences on this reaction
remains unclear. The N-allyl-substituted imines show complete
selectivity for the sterically less congested 1,2-insertion pro-
duct. This selectivity may be a result of the sterically bulky imine
unit directing the orientation of olefin coordination prior to
insertion (Scheme 6), or perhaps by the imine remaining
coordinated to the nickel throughout the reaction, which would
favor the formation of the five-membered chelate product 16 (n
= 1). As the length of the tether is increased, the steric
interactions at the nickel center should become less pro-
nounced, and chelation of the imine should stabilize the
generation of the smaller ring intermediate 17 (n = 2, 3). This
2,1-insertion regioselectivity is also that most commonly found
in systems bearing smaller bite angle ligands (e.g., 2,20-
bipyridyl).19 While the selectivity of olefin insertion is reversed
with longer tether lengths, the regiochemistry of imine inser-
tion remains unchanged, and in all cases, insertion occurs such
that an amide bond is formed.
obtained on 300 or 400 MHz instruments. Unless otherwise stated, all
reagents were purchased from commercial sources and used without
further purification. Liquids were freeze-pump-thawed three times to
degas before use. Diethyl ether was distilled from sodium benzophe-
none. Pentane, methylene chloride, and chlorobenzene were distilled
from CaH2. Deuterated solvents were dried as their protonated analo-
gues but were vacuum-transferred from the drying agent. Ultrahigh-
purity carbon monoxide was used in the reactions. Imines were prepared
by standard procedures from the corresponding aldehyde and amine in
THF at room temperature with magnesium sulfate as the drying agent.
Benzophenone-derived imines were prepared by the reaction of benzo-
phenone with the appropriate amine-HCl salt at room temperature
overnight in methylene chloride. The solution was then filtered and the
solvent removed under vacuum to give the desired imine as a colorless
20
oil. (bipy)NiMe2 and (4,40-dimethylbipyridyl)NiMe221 were prepared
as described in the literature from (tmeda)NiMe222 and the appropriate
ligand. (2,3,8,9-tetramethyl-1,10-phenanthroline)NiMe2 was prepared
in a similar fashion as an insoluble green solid and used in situ without
further purification for the experiment in Table 1. Iminium salts were
prepared via addition of 1.1 equiv of anhydrous HCl in diethyl ether to
the appropriate imine, followed by removal of the ether in vacuo and the
addition of desired counterion salt (i.e., AgSbF6, NaBArf23) in CH2Cl2
for 4 h. The precipitate was removed by filtration and the filtrate pumped
to dryness and used in situ without further purification.
’ CONCLUSIONS
In conclusion, the above results suggest that imines and olefins
are unusually competitive in their insertion propensity into
nickel-carbon bonds. This is despite the larger steric require-
ment of substituted imines and their generally higher barriers to
imine insertion. The relative insertion propensity shows clear
steric and electronic effects and indicates that the superior
-
Synthesis of [(bipy)Ni(CH3)(CH2dCHCH2Nd(H)Tol]þSbF6
(6a). (bipy)Ni(CH3)2 (75 mg, 0.307 mmol) was suspended in THF
(10 mL) and cooled to -40 °C to give an intensely dark green solution.
In a separate vessel [CH2dCHCH2(H)NdCH(p-C6H4CH3)]þSbF6
-
(124 mg, 0.307 mmol) was dissolved in THF (10 mL) and cooled
Scheme 6. Postulated Insertion Pathways for Five- and Six-Membered Lactam Formation
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to-40 °C. The iminium saltwas thenadded totherapidly stirred solution
of (bipy)Ni(CH3)2 over 3 min via pipet. Near the end of the addition the
dark green solution changed to a deep red color. The solution was cooled
to -40 °C for 30 min and then filtered through Celite and recrystallized
from diethyl ether (50 mL) at -40 °C. After 12 h the clear solvent
mixture was decanted, and the solid residue was washed with pentane
(3 ꢀ 5 mL) and then dried under vacuum to yield an orange powder
(112 mg, 64% yield). 1H NMR (400 MHz, CD2Cl2): δ 9.39 (d, J = 11.6
Hz, 2H), 8.40 (s, 1H, C(H)-p-Tol), 8.36 (d, J = 5.6 Hz, 1H), 8.15-8.01
(m, 4H), 7.63-7.54 (m, 2H), 7.41-7.30 (m, 3H), 6.50-6.36 (m, 1H,
CH2CHdCH2), 5.58 (d, J = 18.0 Hz, 1H, CH2CHdCH2), 5.36-5.30
(d, J = 10.9 Hz, 1H, CH2CHdCH2), 4.65 (d, J = 5.4 Hz, 2H,
4.50 (s, 2H, major), 4.41 (s, 2H, minor), 3.96 (d, J = 5.2 Hz, 2H, minor),
3.79 (d, J = 5.2 Hz, 2H, major), 2.78 (s, 3H), 2.32 (s, 3H, minor), 2.21 (s,
3H, major). 13C NMR (126 MHz, CDCl3 65 °C): δ 171.1, 171.0, 159.2,
159.1, 133.2, 132.7, 129.9, 128.7, 127.8, 127.5, 117.6, 116.9, 114.5, 114.1,
55.5, 55.4, 50.6, 49.9, 47.7, 47.6, 21.9, 21.7. IR (KBr): νCO 1650 cm-1
.
Anal. Calcd for C13H17NO2: C, 71.21; H, 7.81; N, 6.39. Found: C, 70.71;
H, 8.15; N, 6.29.
4-Acetyl-1-(4-methylbenzyl)pyrrolidin-2-one (11a). Yield: 41% iso-
lated, oil. 1H NMR (400 MHz, CDCl3): δ 7.20-7.02 (m, 4H), 4.39 (dd,
J = 14.6, 8.3 Hz, 2H), 3.50-3.12 (m, 3H), 2.62 (d, J = 9.8 Hz, 2H), 2.34
(s, 3H), 2.18 (s, 3H). 13C NMR (126 MHz, CDCl3): δ 206.1, 172.2,
137.7, 133.1, 129.7, 128.4, 47.3, 46.5, 43.5, 33.4, 28.6, 21.3. IR (KBr):
νCO 1699 cm-1. Anal. Calcd for C14H17NO2: C, 72.70; H, 7.41; N, 6.06.
Found: C, 72.44; H, 7.85; N, 6.39.
4-Acetyl-1-(4-(trifluoromethyl)benzyl)pyrrolidin-2-one (11b).Yield: 78%
isolated, oil. 1H NMR (400 MHz, CDCl3): δ 7.57 (d, 2H, 8.4 Hz), 7.35 (d,
J= 8.4 Hz, 2H), 4.42 (d, J=11.4Hz, 2H), 3.45(m, 1H), 3.40-3.20 (m, 2H),
2.63 (m, 2H), 2.19 (s, 3H). 13C NMR (126 MHz, CDCl3): δ 206.0, 172.5,
140.3, 128.5, 128.4, 125.9, 125.8, 47.4, 46.3, 43.3, 33.2, 28.7. IR (KBr): νCO
1699 cm-1. Anal. Calcd for C14H14F3NO2: C, 58.95; H, 4.95; N, 4.91. Found:
C, 58.58; H, 5.21; N, 5.18.
CH2CHdCH2), 2.38 (s, 3H, C6H4CH3), 0.09 (s, 3H, Ni-CH3). 13
C
NMR (126 MHz, CD2Cl2): δ 169.1, 157.2, 156.4, 153.1, 149.8, 147.1,
146.1, 141.1, 136.6, 134.0, 129.3, 128.2, 127.7, 127.2, 123.4, 122.5, 115.5,
63.5, 21.4, -1.5. Anal. Calcd for C22H24F6N3NiSb: C, 42.29; H, 3.87; N,
6.72. Found: C, 41.97; H, 3.77; N, 6.55.
InSituGenerationof[(bipy)Ni(COCH3)(CH2dCHCH2Nd(H)-
Tol]þSbF6- (7a). Complex 6a (10 mg, 0.016 mmol) was dissolved in
0.5 mL of CD2Cl2. The solution was transferred to a J. Young NMR tube
and frozen in a liquid-nitrogen bath, the tube was evacuated, and 1 atm of
carbon monoxide was added. Immediate 1H NMR analysis showed that
7a was formed within 5 min at ambient temperature, along with small
amounts of the subsequent imine and/or olefin insertion products.
In situ 1H NMR analysis is consistent with this structure.8 1H NMR (300
MHz, CD2Cl2): δ 9.51 (d, J = 7.7 Hz, 2H), 8.52 (s, 1H, C(H)-p-Tol),
8.18-8.01 (m, 4H), 7.88 (br, 1H), 7.65-7.30 (m, 5H), 6.33 (br, 1H,
CH2CHdCH2), 5.64 (d, J = 19.9 Hz, 1H, CH2CHdCH2), 5.36 (d,
J = 10.9 Hz, 1H, CH2CHdCH2), 4.65 (m, 2H, CH2CHdCH2), 2.54
(s, 3H (NiCOCH3), 2.32 (s, 3H, C6H4CH3).
4-Acetyl-1-(4-methoxybenzyl)pyrrolidin-2-one (11c). Yield: 21% iso-
lated, oil. 1H NMR (400 MHz, CDCl3): δ 7.18 (d, J = 8.4 Hz, 2H), 6.88 (d,
J = 8.4 Hz, 2H), 4.44 (d, 1H, J = 11.2 Hz, 2H), 4.32 (d, J = 11.2 Hz, 1H),
3.79 (s, 3H), 3.44 (m, 1H), 3.35 (m, 1H), 3.25 (m, 1H), 2.66 (m, 2H), 2.16
(s, 3H). 13C NMR (126 MHz, CDCl3): δ 206.15, 171.1, 159.4, 129.7,
128.1, 114.3, 55.5, 47.3, 46.2, 43.5, 33.4, 28.7. IR (KBr): νCO 1699 cm-1
.
Anal. Calcd for C14H17NO3: C, 68.00; H, 6.93; N, 5.66. Found: C, 67.57; H,
7.15; N, 5.29.
4-Acetyl-1-benzhydrylpyrrolidin-2-one (11h). Yield: 77% isolated,
oil. 1H NMR (400 MHz, CDCl3): δ 7.40-7.20 (m, 6H), 7.20-7.08 (m,
4H), 6.57 (s, 1H), m, 3.45-3.35 (m, 1H), 3.33-3.19 (m, 2H), 2.71 (d,
J = 11.6 Hz, 2H), 2.14 (s, 3H). 13C NMR (126 MHz, CDCl3): δ 206.3,
172.5, 138.5, 138.2, 128.9, 128.8, 128.6, 128.5, 128.0, 127.9, 58.9, 45.3,
43.6, 33.5, 28.8. IR (KBr): νCO 1699 cm-1. Anal. Calcd for C19H19NO2:
C, 77.79; H, 6.53; N, 4.77. Found: C, 78.20; H, 7.02; N, 4.34. HRMS:
m/z calcd for C18H20NO2þ 294.148 86, found 294.148 75.
General Procedure for the Cyclocarbonylation of Imines.
(bipy)NiMe2 (200 mg, 0.846 mmol) was dissolved in 10 mL of dry
methylene chloride to give an intensely blue-green solution. One
equivalent of iminum salt was dissolved in 10 mL of methylene chloride
and added dropwise to a stirred solution of (bipy)NiMe2. The solution
rapidly turned deep red near the end of the addition, and the evolution of
methane was noted. The solution was then transferred to a 300 mL reaction
bomb and frozen in a liquid nitrogen bath, the bomb was evacuated, and 1
atm of carbon monoxide was added. The mixture was warmed to room
temperature and stirred for 48 h. The organic products were then cleaved
from the nickel center by addition of a saturated solution of KCN/MeOH.
This was accompanied by a rapid color change from deep red to pale yellow.
The solvent was removed in vacuo, the residue was dissolved in methylene
chloride, this solution was filtered through Celite, and the solvent was
removed again. The resulting oil was then dissolved in ethyl acetate, washed
twice with 10% HCl solution, and purified by silica gel column chroma-
4-Acetyl-1-benzhydrylpiperidin-2-one (13). Yield: 20% isolated, oil.
1H NMR (400 MHz, CDCl3): δ 7.40-7.15 (m, 11H, aromatic and
NC(H)Ph2, as assigned by 2D NMR), 3.19 (m, 1H), 3.00-2.81 (m, 2H),
2.69 (m, 2H), 2.19 (s, 3H), 2.08 (m, 1H), 1.85 (m, 1H). 13C NMR (126
MHz, CDCl3): δ 208.3 (CH3COC), 168.7 (CON-), 138.7, 138.4,
129.7, 128.7, 128.2, 128.0, 127.5(4), 127.5, 60.0 (CHPh2), 45.7, 42.8,
33.9, 28.3, 25.3.25 IR (KBr): νCO 1699 cm-1 Anal. Calcd for
C20H21NO2: C, 78.15; H, 6.89; N, 4.56. Found: C, 78.27; H, 7.20; N,
4.34. HRMS: m/z calcd for C20H22NO2þ 308.164 51, found 308.164 42.
1-Benzhydryl-3-(2-oxopropyl)pyrrolidin-2-one (14). Yield: 60% iso-
lated, oil. 1H NMR (400 MHz, CDCl3): δ 7.40-7.20 (m, 6H), 7.20-7.14
(m, H), 6.58 (s, 1H), 3.23-3.02 (m, 3H), 2.90 (m, 1H), 2.59 (m, 1H),
2.35 (m, 1H), 2.19 (s, 3H), 1.7 (m, 1H). 13C NMR (126 MHz, CDCl3,
65 °C): δ 207.1, 176.0, 138.8, 138.7, 129.1, 128.8, 128.7, 128.2, 127.9,
tography. The identity of 11g was confirmed by comparison of 1H and 13
C
NMR data to those of the known compound.24
N-Allyl-N-(4-methylbenzyl)acetamide (9a). Yield: 41% isolated, oil.
The product was observed as a mixture of amide rotamers at ambient
1
temperature. H NMR (400 MHz, CDCl3): δ 7.20-7.00 (m, 4H),
5.81-5.65 (m, 1H), 5.24-5.04 (m, 2H), 4.75 (s, 2H, major rotamer),
4.43 (s, 2H, minor rotamer), 3.98 (d, 2H, J = 7.6 Hz, minor), 3.79 (d, 2H,
J = 7.6 Hz, major), 2.38 (s, 3H, minor), 2.31 (s, 3H, major), 2.38 (s, 3H,
minor), 2.36 (s, 3H, major). 13C NMR (126 MHz, CDCl3): δ 171.1,
169.8, 137.5, 137.3, 134.7, 133.2, 132.6, 129.8, 129.5, 128.5, 126.5, 117.7,
117.0, 50.8, 49.9, 48.0, 47.9, 21.8, 21.6, 21.4, 21.3. IR (KBr): νCO
1650 cm-1. Anal. Calcd for C13H17NO: C, 76.81; H, 8.43; N, 6.89.
Found: C 76.41; H, 8.72; N, 7.23.
N-Allyl-N-(4-methoxybenzyl)acetamide (9c). Yield: 61% isolated,
oil. The product was observed as a mixture of amide rotamers at ambient
temperature. 1H NMR (400 MHz, CDCl3): δ 7.35 (d, J = 8.8 Hz, 2H,
major), 7.18 (d, J = 8.8 Hz, 2H, minor), 6.78 (d, J = 9.6 Hz, 2H, minor),
6.62 (d, J = 9.6 Hz, 2H, major), 5.81-5.61 (m, 1H), 5.24-5.07 (m, 2H),
127.6, 59.1, 44.9, 42.9, 38.2, 30.4, 25.8.25 IR (KBr): νCO 1699 cm-1
.
Anal. Calcd for C20H21NO2: C 78.15; H, 6.89%; N, 4.56. Found: C,
78.27; H, 7.20; N, 4.43. HRMS: m/z calcd for C20H22NO2þ 308.164 51,
found 308.163 99.
1-Benzhydryl-3-(2-oxopropyl)piperidinone (15). Yield: 72% iso-
lated, oil. 1H NMR (400 MHz, CDCl3): δ 7.40-7.10 (m, 11H, aromatic
and NC(H)Ph2, as assigned by 2D NMR), 3.18-2.84 (m, 4H), 2.65 (m,
1H), 2.19 (s, 3H), 1.95 (m, 1H), 1.80 (m, 2H), 1.58 (m, 1H). 13C NMR
(126 MHz, CDCl3): δ 207.7, 172.4, 139.1, 129.5, 128.9, 128.7, 128.6,
128.5, 127.6, 127.5, 60.3, 45.7, 44.4, 38.4, 30.6, 27.1, 22.7.25 IR (KBr):
νCO 1699 cm-1 Anal. Calcd for C21H23NO2: C, 78.47; H, 7.21; N, 4.36.
Found: C, 78.11; H, 7.63; N, 4.22.
1900
dx.doi.org/10.1021/om1011566 |Organometallics 2011, 30, 1896–1901

Organometallics
ARTICLE
’ ASSOCIATED CONTENT
(12) On the basis of 72.8 and 147 kcal/mol for an average C-N
bond and CdN bond, respectively: Sandorfy, C. The Chemistry of the
Carbon-Nitrogen Double Bond; Pati, S., Ed.; Wiley: New York, 1970; p 1.
(13) Svejda, S. A.; Johnson, L. K.; Brookhart, M. J. Am. Chem. Soc.
1999, 121, 10634.
(14) The insertion of imine into nickel-acyl bonds may not proceed
in the concerted fashion often observed for alkenes, and the barriers may
reflect that of concerted imine insertion, an intra- or intermolecular
nucleophilic attack of imine on the acyl ligand, conversion of η1- to an
η2-coordinated imine, or a combination of these. Nevertheless, the
generation of the formal imine insertion product is a reaction with a
higher barrier than that with simple alkenes. We thank a reviewer for
noting this.
Supporting Information. 1H and 13C NMR data for
S
b
compounds 9 and 11 and 1H and 13C NMR and 2D NMR data
for compounds 13-15. This material is available free of charge
via the Internet at http://pubs.acs.org.
’ AUTHOR INFORMATION
Corresponding Author
*E-mail: bruce.arndtsen@mcgill.ca.
(15) Styrene typically undergoes nickel-catalyzed oligomerization at
room temperature in 0.1-2 h: (a) Ascenso, J. A.; Dias, A. R.; Gomes,
P. T. Macromolecules 1996, 29, 4172. (b) Ascenso, J. A.; Dias, A. R.;
Gomes Macromolecules 1989, 22, 998.
(16) While complex 7a undergoes imine and alkene insertion too
rapidly to be isolated, in situ 1H NMR analysis shows it to be analogous
to previously generated nickel-acyl complexes:8: see the Experimental
Section for details.
’ ACKNOWLEDGMENT
We thank the National Sciences and Engineering Research
Council of Canada (NSERC), the Canadian Foundation for
Innovation (CFI), and the FQRNT supported Center for Green
Chemistry and Catalysis (CGCC) for funding this research.
(17) NMR analysis of the mixture of nickel-chelated amide products
in Scheme 3 shows complex 8a (1H NMR (CD2Cl2): δ 4.39 (s, 1H,
C(H)-p-Tol), 2.15 (s, 3H, COCH3)) and two sets of signals for 10a (1H
NMR (CD2Cl2): δ 4.10 (s, 1H, C(H)-p-Tol) and 4.06 (s, 1H C(H)-p-
Tol); 2.11 (s, 3H, COCH3) and 2.07 (s, 3H, COCH3)), in a ca. 1:1 ratio,
on the basis of integration of CH3CO- reasonances. While products 8
and 10 could not be separated for full characterization, these data are
similar to those for previously isolated metal-chelated amides,8,9 and
cleavage of the amide ligands with KCN/MeOH was used to confirm the
amide ligand structure.
(18) The nickel complex in eq 2 was generated in situ using the
general procedure given in Table 1. Before cleavage of the amide ligand
with KCN/MeOH, the solvent was removed, the nickel complex was
dissolved in CD3CN, and the solution was heated to 70 °C and
monitored by 1H NMR spectroscopy.
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