Nickel-Copper-Catalyzed C(sp2)- N Cross-Coupling of Cyclic and Bridged Amides: An Access to Cyclic Enamides and Alkenyl Vince Lactams

Article abstract of DOI:10.1002/adsc.201500457

An efficient C(sp²)- N cross-coupling of styrenyl and vinyl halides with cyclic and bridged amides catalyzed by nickel acetonylacetonate [Ni(acac)₂] and copper(I) iodide (CuI) in the absence of any ligand has been developed. The reaction conditions are optimized to give the maximum yield of products using cesium carbonate (Cs₂CO₃) (2.0 equiv.) in N-methyl-2-pyrrolidinone (NMP) at 110 C under argon in the presence of Ni(acac)₂/CuI (10 mol% each). A series of alkenyl derivatives of Vince lactams (bridged amides) and cyclic amides are obtained by this procedure. Halogen-containing styrenyl bromides also underwent coupling with amides to provide the products. The coupling is highly chemoselective as during the reactions the halogens (Br, Cl, F) on the aromatic ring remained intact and these can be used for further functionalization to make these enamides more useful. Although the (E)-styrenyl halides produced the corresponding (E)-styrenyl enamides, reactions with (Z)-styrenyl halides produced 1,3-di-ynes instead of (Z)-styrenyl enamides. This may be explained by the possibility of E₂ type elimination of (Z)-styrenyl halides in the presence of a strong base like cesium carbonate followed by homocoupling. This catalyst system works efficiently for the N-arylation too along with N-styrenylation and vinylation. The bridged as well as cyclic amides successfully coupled with substituted aryl halides to provide the corresponding products. In general, the reactions are clean and high yielding. The operations are very simple and the products are obtained pure by standard column chromatography. The reaction is compatible with variety of amides and alkenyl bromides. The roles of nickel acetonylacetonate and copper(I) iodide in this reaction have been established and a possible reaction pathway has been outlined. The significant feature of this protocol is the alkenylation of Vince lactams via C(sp²)- N cross-coupling, which has not been reported so far and these products may have much potential in the pharmaceutical industry.

Full text of DOI:10.1002/adsc.201500457

FULL PAPERS
DOI: 10.1002/adsc.201500457
2
À
Nickel–Copper-Catalyzed C(sp ) N Cross-Coupling of Cyclic and
Bridged Amides: An Access to Cyclic Enamides and Alkenyl
Vince Lactams
a
a
a,
Pintu Maity, Debasish Kundu, and Brindaban C. Ranu *
a
Department of Organic Chemistry, Indian Association for the Cultivation of Science, Jadavpur, Kolkata – 700032, India
E-mail: ocbcr@iacs.res.in
Received: May 8, 2015; Revised: August 5, 2015; Published online: October 28, 2015
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201500457.
2
Abstract: An efficient C(sp )ÀN cross-coupling of sibility of E type elimination of (Z)-styrenyl halides
2
styrenyl and vinyl halides with cyclic and bridged in the presence of a strong base like cesium carbon-
amides catalyzed by nickel acetonylacetonate ate followed by homocoupling. This catalyst system
[
Ni(acac) ] and copper(I) iodide (CuI) in the absence works efficiently for the N-arylation too along with
2
of any ligand has been developed. The reaction con- N-styrenylation and vinylation. The bridged as well
ditions are optimized to give the maximum yield of as cyclic amides successfully coupled with substituted
products using cesium carbonate (Cs CO ) aryl halides to provide the corresponding products.
2
3
(
1
2.0 equiv.) in N-methyl-2-pyrrolidinone (NMP) at In general, the reactions are clean and high yielding.
108C under argon in the presence of Ni(acac) /CuI The operations are very simple and the products are
2
(
10 mol% each). A series of alkenyl derivatives of obtained pure by standard column chromatography.
Vince lactams (bridged amides) and cyclic amides The reaction is compatible with variety of amides
are obtained by this procedure. Halogen-containing and alkenyl bromides. The roles of nickel acetonyl-
styrenyl bromides also underwent coupling with acetonate and copper(I) iodide in this reaction have
amides to provide the products. The coupling is been established and a possible reaction pathway has
highly chemoselective as during the reactions the been outlined. The significant feature of this protocol
2
halogens (Br, Cl, F) on the aromatic ring remained is the alkenylation of Vince lactams via C(sp )ÀN
intact and these can be used for further functionali- cross-coupling, which has not been reported so far
zation to make these enamides more useful. Al- and these products may have much potential in the
though the (E)-styrenyl halides produced the corre- pharmaceutical industry.
sponding (E)-styrenyl enamides, reactions with (Z)-
styrenyl halides produced 1,3-di-ynes instead of (Z)- Keywords: copper; cross-coupling; nickel; Vince lac-
styrenyl enamides. This may be explained by the pos- tams; vinyl halides
Introduction
lactams is not adequately addressed and this prompt-
ed us to start work in this area.
Enamides are of much importance as they constitute
The transition metal-catalyzed cross-coupling reac-
[
1]
2]
the key structural motifs in many natural products
and are used as versatile synthetic intermediates.
tion is a powerful tool for CÀC and CÀheteroatom
[
[5]
2
bond formation. The coupling with a C(sp ) center
3
The cyclic, particularly the bicyclic (bridged) enamide, is usually more challenging than with a C(sp ) one.
2
Vince lactam, has received considerable current atten- The C(sp )ÀN coupling is an important reaction as it
[6]
tion because of its presence as an active scaffold in leads to many pharmaceutically active molecules.
[3]
many life-saving drugs and its use as building block
Among various N-nucleophiles such as N-heterocy-
[4]
for the synthesis of several therapeutic agents. Thus cles, amines, anilines and amides the coupling with
an easy access to diverse derivatives of Vince lactam amides is a difficult one due to the their less reactivity
is of much importance for screening of these pharma- for conjugation of the lone pair of electrons of the N-
ceutically useful compounds. Surprisingly, the synthe- center with the adjacent carbonyl moiety. Although
2
sis of substituted, particularly N-vinyl/alkenyl Vince C(sp )ÀN coupling with amides was achieved by Pd
Adv. Synth. Catal. 2015, 357, 3617 – 3626
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Pintu Maity et al.
FULL PAPERS
1
,3-dienyl bromide (2a). The results are summarized
in Table 1. The reaction using Ni(acac) or nickel
2
chloride (NiCl ) in the presence of a reducing agent,
2
zinc (Zn), did not lead to any product (Table 1, en-
tries 1 and 2). Use of several N-base ligands (L1, L2,
L3, L4 and L5) together with NiCl provided marginal
2
yields of product (Table 1, entries 3–7). Interestingly,
addition of CuI (10 mol%) along with NiCl ·6H O in
2
2
the presence of a reducing agent, Zn, slightly im-
proved the yield (Table 1, entry 8). However, use of
[
a]
Table 1. Optimization of the reaction conditions.
Scheme 1. Nickel-catalyzed N-vinylation of amides via
2
C(sp )ÀN cross-coupling.
[
7]
catalysis, this reaction is associated with disadvan-
tages of high cost of catalyst, and tedious separation
of Pd catalysts from polar reaction medium, especially
[
8]
in the later stages of the reaction. Ullmanꢁs Cu-cata-
[
9]
lyzed N-arylation of amines and Goldbergꢁs Cu-cat-
alyzed N-arylations of amides have been widely used
since the last decades. However, these procedures
often require high temperature (nearly 2008C), ex-
[10]
pensive and toxic dinitrogen ligands. Later Chan re-
ported an alternative for the arylation of amides with
triarylbismuth in the presence of cupric acetate at
room temperature using a stoichiometric amount of
Cu catalyst. A couple of reports on the Cu-catalyzed
cross-coupling of amides with potassium alkenyltri-
[
11]
[12]
fluoroborate salts,
acids
vinyl halides
and arylboronic
[b]
Entry Catalyst
Solvent Base
Time
h]
Yield
[
13]
in the presence of ligand are also available.
[
[
14]
Recently, Teo et al. reported a cobalt-catalyzed pro-
tocol for the N-arylation of benzamides with aryl
iodide in the presence of a dinitrogen ligand whereas
Singh et al. demonstrated a Ni-catalyzed one using
arylboronic acids. However, to the best of our knowl-
edge, a metal-catalyzed alkenylation of bridged amide
by coupling reaction has not been reported so far.
Considering the importance of enamides and func-
1
2
3
4
5
6
7
8
Ni(acac)2
NMP
NMP
Cs CO 24
Cs CO 24
2
–
2
3
[
c]
NiCl ·6H O
trace
trace
10%
15%
11%
16%
20%
2
2
3
[
15]
NiCl
2
·6H
2
O/L1 NMP
Cs
2
CO
3
24
NiCl ·6H O/L2 NMP
Cs CO 24
2 3
2
2
NiCl ·6H O/L3 NMP
Cs CO 24
2 3
2
2
NiCl ·6H O/L4 NMP
Cs CO 24
2
2
2 3
NiCl ·6H O/L5 NMP
Cs CO 24
2 3
2
2
NiCl ·6H O/
NMP
Cs CO 24
2
2
2
3
[
16]
tionalized Vince lactams,
we sought to develop
CuI
a more convenient protocol for the alkenylation of
9
Ni(acac)
Ni(acac)
Ni(acac) /CuI
Ni(acac) /CuI
Ni(acac)
Ni(acac) /CuI
Ni(acac) /CuI
Ni(acac) /CuI
Ni(acac) /CuI
2
/CuI
NMP
Cs
Cs
2
CO
CO
3
3
15
15
75%
40%
trace
20%
trace
10%
trace
45
bridged amides using a less expensive metal and 10
/CuCl NMP
2
2
11
NMP
NMP
toluene Cs
DMF
DMSO Cs CO 15
NMP
NMP
NMP
K CO 20
avoiding a ligand. Being motivated with our recent
2
2 3
[
17a]
12
13
K PO 20
3
2
4
works on carbon-carbon
bond formation
and carbon-heteroatom
[
17b]
/CuI
2
2
CO
3
15
using an Ni/Cu system we report
1
1
1
1
1
4
5
6
7
8
Cs CO 15
2 3
2
2
here a Ni-catalyzed C(sp )ÀN cross-coupling of styr-
enyl/vinyl halides with bridged and cyclic amides in
the presence of CuI (Scheme 1).
2
2
3
[d]
[e]
Cs CO 15
2
2 3
Cs CO 15
–
2
2
3
CuI
Cs CO 20
2
trace
3
[
a]
Reaction conditions: A mixture of 1a (1.0 mmol), 2a
1.0 mmol), 10 mol% Ni catalyst and Cs CO (2.0 mmol)
Results and Discussion
(
2
3
was heated at 1108C under an argon atmosphere.
Yield of isolated pure products.
To standardize the reaction conditions, a series of ex-
periments was carried out with variation of reaction
parameters such as catalyst, base, solvent, tempera-
ture and time for a representative reaction of 2-azabi-
cyclo[2.2.1]hept-5-en-3-one (1a) and 4-phenyl-(E,E)-
[b]
[c]
1
5
.5 equiv. Zn were used.
mol% each of Ni(acac) /CuI were used.
[
[
d]
e]
2
The reaction was performed at room temperature
(308C).
3
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FULL PAPERS
Nickel–Copper-Catalyzed C(sp )ÀN Cross-Coupling of Cyclic and Bridged Amides
Table 2. Ni/Cu co-catalyzed coupling of amides and vinyl
halides.
Table 2. (Continued)
[
a]
[
[
a]
b]
Reaction conditions: cyclic amide (2.0 mmol), vinyl bro-
mide (1.0 mmol), Ni(acac) (10 mol%), CuI (10 mol%),
2
Cs CO (2.0 equiv.), NMP (3 mL), 1108C, 15 h, under
2
3
argon atmosphere.
Yield of isolated pure products.
Ni(acac) /CuI (10 mol% each), CS CO as a base and
2
2
3
NMP (N-methyl-2-pyrrolidinone) as a solvent in the
absence of a ligand and reducing agent produced the
best result (Table 1, entry 9). Use of copper chloride
(
CuCl) instead of CuI reduced the yield (Table 1,
entry 10). The reaction did not proceed using
a weaker base such as K CO and K PO in place of
2
3
3
4
CS CO (Table 1, entries 11 and 12). Use of toluene
2
3
or dimethyl sulfoxide (DMSO) failed to initiate the
reaction; however in N,N-dimethylformamide (DMF)
the reaction progressed marginally (10%) (Table 1,
entries 13–15). To check the catalyst loading, use of
5
mol% of Ni(acac) /CuI instead of 10 mol% de-
2
creased the yield of product (Table 1, 16). The reac-
tion did not occur at room temperature (Table 1,
entry 17). Use of CuI (10 mol%) without Ni catalyst
led to only a trace amount of product (Table 1,
entry 18). Thus, in a typical experimental procedure,
a mixture of bridged/cyclic amide (2.0 mmol), vinyl
halide (1.0 mmol) and CS CO (2.0 equiv.) in NMP
2
3
was heated at 1108C under argon in the presence of
Ni(acac) /CuI (10 mol% each) for a certain period of
2
time (monitored by TLC). Standard work-up and
column chromatography provided the pure products.
A series of diversely substituted styrenyl and vinyl
2
halides underwent C(sp )ÀN coupling with a variety
of bridged and cyclic amides under the standardized
conditions to afford the corresponding enamides. All
the products are summarized in Table 2.
4
-Phenyl-(E,E)-1,3-dienyl bromide and 4-phenyl-3-
pentyl-(E,E)-1,3-dienyl bromides underwent efficient
coupling with 2-azabicyclo[2.2.1]hept-5-en-3-one to
give the corresponding bridged enamides (3a, 3b).
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Table 3. Ni/Cu co-catalyzed coupling of amides and aryl hal-
[
a]
ides.
Scheme 2. Reaction between cis-vinyl bromide and amide.
Styrenyl bromides containing naphthyl and Me moiet-
ies in the aromatic ring coupled with 2-azabicy-
clo[2.2.1]hept-5-en-3-one, oxazolidinone, pyrolidinone
and azepan-2-one to produce the corresponding en-
amides without any difficulty (3c, 3d, 3e, 3l, 3m, 3p
and 3q). In general, styrenyl bromides containing hal-
ogen substituents at o-, m-, and p-positions underwent
coupling with amides to provide the products (3f, 3g,
3
h, 3n, 3o, 3s, 3t and 3v). The coupling is highly che-
moselective as during the reactions the halogens (Br,
Cl, F) on the aromatic ring remained intact and these
can be used for further functionalization to make
these enamides more useful. Bromomethylenecyclo-
hexene and [(E)-2-bromovinyl]cyclohexane were
[
[
a]
b]
Reaction conditions: cyclic amide (2.0 mmol), vinyl bro-
mide (1.0 mmol), Ni(acac) (10 mol%), CuI (10 mol%),
Cs CO (2.0 equiv.), NMP (3 mL), 1108C, 15 h, under
argon atmosphere.
Yield of isolated pure products.
2
2
3
2
compatible in this C(sp )ÀN coupling to produce the
corresponding enamides (3i and 3j). 4- Phenyl-3-
pentyl-(E,E)-1,3-dienyl bromide coupled with 4-meth-
ylquinolin-2(1H)-one to provide the compound, 3r
which may be of potential for nucleic acid detec-
[
18]
tion.
went successful coupling with 2-azabicyclo[2.2.1]hept-
-en-3-one to afford the product (3k). The electron-
(1E,3E)-1-Bromodeca-1,3-diene also under-
5
donating (Me) and mildly electron-withdrawing (F,
Cl, Br) group-substituted styrenyl bromides under-
went reactions cleanly (3d, 3e, 3l, 3f, 3g, 3h, 3n, 3o, 3s,
3
t and 3v). However, reactions with strong electron-
withdrawing groups (CO Me and NO )-substituted
2
2
Scheme 3. N-Arylation of benzamide.
styrenyl bromides are not successful.
Although the (E)-styrenyl halides produced the cor-
responding (E)-styrenyl enamides (Scheme 2), reac- (Scheme 3) although the reaction with a primary ali-
tion with (Z)-styrenyl halides produced 1,3-di-ynes in- phatic amide (butyl amide) did not succeed.
stead of (Z)-styrenyl enamides. This may be explained
In general, the reactions are clean and high yield-
by the possibility of E type elimination of (Z)-styren- ing. The operations are very simple and the products
2
yl halides in the presence of a strong base like are obtained pure by standard column chromatogra-
[
19]
Cs CO
followed by homocoupling.
phy. The reaction is compatible with a variety of
2
3
This catalyst system works efficiently for the N-ary- amides and alkenyl bromides. To compare our proce-
[12d]
lation too along with N-styrenylation and N-vinyla- dure with a reported one,
when we performed a re-
tion. The bridged as well as cyclic amides successfully action of Vince lactam (bridged amide) and 1-[(E)-2-
coupled with substituted aryl halides to provide the bromovinyl]-4-methylbenzene under the reported
corresponding products (Table 3, 4a, 4b, 4c, 4d and conditions using CuI (10 mol%), N,N-dimethylglycine
4
e).
(20 mol%), Cs CO (2 mmol) and dioxane at 808C for
2 3
The standardized conditions are also applicable for 12 h the coupled product was obtained in only 30%
the coupling of acyclic amides and aryl halides yield. This demonstrates the superior efficacy of our
procedure in the alkenylation of bridged amides.
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Nickel–Copper-Catalyzed C(sp )ÀN Cross-Coupling of Cyclic and Bridged Amides
We then turned our attention to deduce the mecha- Table 4. Control experiments to explore the role of acetyl-
acetone and Ni-Cu catalyst.
nism for this Ni/Cu-mediated coupling. To check the
involvement of a radical process, the coupling of 1a
and 2a was performed in the presence of TEMPO
(
radical quencher), THF (electron receptor), nitroar-
ene (electron acceptor) separately. Notably, the reac-
tions remained unaffected. The high stereoselectivity
in coupling also does not suggest the presence of
a radical intermediate due to the inherent nature of
vinyl radicals to undergo rapid inversion of conver-
[
20]
sion. So the possibility of radical pathway is unlike-
ly for this reaction. Increase of steric hindrance of the Expt. Catalytic conditions
reactant decreases the rate of the reaction and this in- no.
dicates that the reaction is more likely to follow an
Product,
yield
1
2
NiCl (10 mol%), CuI (10 mol%),
3a, trace
3a, 20%
2
oxidative addition and reductive elimination pathway.
During optimization we have observed that the re-
action did not proceed in the presence of Ni(acac) or
Cs CO , 1108C, NMP, 15 h
2
3
NiCl (10 mol%), CuI (10 mol%),
2
2
Zn/PPh (20 mol%), Cs CO , 1108C,
3
2
3
CuI alone. It clearly indicates the involvement of
a co-operative Ni/Cu catalytic system for the reaction.
In principle, there are two possibilities involving
either copper or nickel in the catalytic cycle. If we
consider the reaction to be catalyzed by copper, it
may proceed through the Cu(I)/Cu(III) oxidative ad-
dition. But it appears very unlikely due to the high
redox potential of the Cu(I)-Cu(III) system in ligand-
free conditions.
We then considered catalysis by nickel compounds.
The
nickel(II) catalysts are well explored to perform
cross-coupling reactions at C(sp2) centres through
Ni(0)-Ni(II) oxidative addition-reductive elimination
pathway where an initial reduction of Ni(II) occurs by
a reducing agent such as Zn, Grignard reagents, etc.
So, to find out a possible reducing agent for the initial
NMP, 15 h
3
4
5
NiCl (10 mol%), Zn (20 mol%),
3a, trace
3a, trace
3a, 60%
2
Cs
CO , 1108C, NMP, 15 h
2
3
CuI (10 mol%), Zn (20 mol%),Cs CO ,
2
3
1108C, NMP, 15 h
NiCl (10 mol%), CuI (10 mol%),
2
acetylacetone (20 mol%), Cs CO ,
2
3
1
108C, NMP, 15 h
CuI (10 mol%), acetylacetone
20 mol%), Cs CO , 1108C, NMP, 15 h
6
7
8
9
3a, trace
[
21]
(
2
3
Cu(acac) (10 mol%), Cs CO , 1108C,
3a, not
formed
2
2
3
NMP, 15 h
NiBr (10 mol%), Cu(acac) (10 mol%), 3a, not
2
2
Cs
CO
2
, 1108C, NMP, 15 h
3
formed
3a, not
formed
Ni(acac) (10 mol%), Cu(acac)
2
2
(10 mol%), Cs CO , 1108C, NMP, 15 h
2 3
reduction of Ni(II) to Ni(0) in our system, several so the possibility of catalysis by CuI in the presence
control experiments were performed (Table 4, expts. of acetylacetone (present in the reaction medium)
1–5). It has been observed that in the presence of without any involvement of nickel may be considered.
NiCl and CuI only a trace amount of product was ob- Thus to check the involvement of Cu catalysis, further
2
tained (expt. no. 1). However, addition of either Zn experiments were performed (Table 4, expt. 6–9). The
or PPh (20 mol%) along with NiCl /CuI triggered the reactions using CuI and acetylacetone (expt. 6) and
3
2
reaction leading to 20% yield (expt. no. 2). This ex- Cu(acac) (expt. 7) in the absence of Ni did not pro-
2
periment indicates that a reduction of Ni(II) to Ni(0) duce any product. We also performed the coupling re-
is one of the vital parameters for this reaction. The re- action with Cu(acac)2 and NiBr2 (expt. 8) and
action was not successful using NiCl (10 mol%)/Zn Cu(acac) and Ni(acac) (expt. 9) and both these ex-
2
2
2
(
(
20 mol%) (expt. no. 3) and CuI (10 mol%)/Zn periments did not lead to a successful result. Thus it is
20 mol%) (expt. no. 4) catalytic systems separately. quite logical to conclude that in the absence of either
Interestingly, the reaction with the combined NiCl2/ Cu(I) or Ni(acac) the reaction is not initiated. The
2
CuI system in presence of 20 mol% acetylacetone essential parameter is the combined co-operative
leads to the desired product in 60% yield (expt. no. effect of Ni(acac) and CuI which only leads to reac-
2
5).
tion. Hence the involvement of Cu(acac) in this reac-
2
Based on these results it may be concluded that the tion is ruled out.
acetylacetone moiety in Ni(acac) is responsible for
Thus, we propose a mechanism for this Ni–Cu-cata-
2
the reduction of Ni(II) to Ni(0) which subsequently lyzed CÀN cross-coupling reaction as outlined in
[
17]
takes part in oxidative addition. We then concen- Scheme 4. The reaction is initiated by acetylaceto-
trated our attention to investigate the precise function nate-facilitated in situ reduction of Ni(II) to Ni(0)
of Ni and Cu in this reaction. As stated earlier, O-li- which then undergoes oxidative addition with vinyl
gands also facilitate Cu(I)-Cu(III) oxidative addition, halide to form intermediate A. In another cycle Cu(I)
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Pintu Maity et al.
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Experimental Section
General Methods
IR spectra were taken as thin films for liquid compounds
and as KBr pellets for solids. NMR spectra were recorded at
1
3
1
00, 400 and 500 MHz for H spectra and at 75, 100 and
1
3
25 MHz for C spectra in CDCl solutions. Ni(acac) and
3
2
CuI were purchased from Sigma–Aldrich chemicals. Vinyl
halides were purchased from Aldrich Chemicals and all styr-
enyl halides were prepared using previously reported proto-
[
17c]
cols.
Elemental analyses were done at our Institute with an au-
toanalyzer. HR-MS analysis was performed in a Qtof mass
analyzer using ESI ionization method
Representative Experimental Procedure for the
Coupling of (1S,4R)-2-Azabicyclo[2.2.1]hept-5-en-3-
one and 1-[(1E,3E)-4-Bromobuta-1,3-dienyl]benzene
A mixture of 2-azabicyclo[2.2.1]hept-5-en-3-one (218 mg,
2.0 mmol),
1-[(1E,3E)-4-bromobuta-1,3-dienyl]benzene
(
(
209 mg, 1.0 mmol), Cs CO (650 mg, 2 mmol), Ni(acac)2
26 mg, 10 mol%), CuI (20 mg, 10 mol%) and NMP (3 mL)
2
3
was heated at 1108C under an argon atmosphere for 15 h
(TLC). Then the reaction mixture was allowed to cool and
extracted with ethyl acetate (3”25 mL). Then the extract
was washed with water (2”10 mL) and the organic phase
was dried over anhydrous Na SO and evaporated under re-
Scheme 4. Possible mechanistic pathway.
2
4
duced pressure to give the crude product which was purified
by column chromatography over silica gel (hexane/ethyl
acetate 85:15) to provide the pure product as yellowish
interacts with amide in the presence of a base leading
to the formation of amide-Cu(I) intermediate B
through the chelation by nitrogen. Then transfer of
amide species occurs from Cu(I) centre to Ni(II)
centre via transmetallation between A and B leading
to the formation of intermediate C. Finally reductive
elimination from intermediate C leads to the product
1
gummy liquid; yield: 177 mg (75%). H NMR (300 MHz,
CDCl ): d=2.27 (d, J=8.1 Hz, 1H), 2.34–2.38 (m, 1H),
3
3
.44–3.46 (m, 1H), 4.70–4.72 (m, 1H), 5.84 (dd, J =14.1 Hz,
1
J =10.5 Hz, 1H), 6.45 (d, J=15.6 Hz, 1H), 6.66–6.94 (m,
2
13
5
H), 7.18–7.20 (m, 1H), 7.21–7.37 (m, 4H); C NMR
(
125 MHz, CDCl ): d=53.5, 57.0, 61.4, 110.2, 126.0 (2C),
3
with regeneration of active catalytic species Ni(0) 127.0, 127.2, 127.3, 128.7 (2C), 129.1, 137.8, 139.0, 139.2,
À1
which takes part in the next cycle.
176.3; IR (neat): n=2923, 2852, 1701, 1683, 1650, 1541 cm ;
anal. calcd. for C H NO: C 80.98, H 6.37, N 5.90; found: C
1
6
15
80.94, H 6.41, N 5.96%.
This procedure was followed for all the reactions listed in
Table 2, Table 3 and Scheme 3. All these compounds except
Conclusions
six (4a–4e and 5a) are new and have been characterized by
their spectroscopic data (IR, H NMR, C NMR), HR-MS
and elemental analysis.
In conclusion, we have demonstrated an efficient
1
13
2
C(sp )ÀN cross-coupling of styrenyl/vinyl halides with
bridged (Vince lactam) and cyclic amides catalyzed
(
1S,4R)-2-[(1E,3E)-3-Benzylideneoct-1-enyl]-2-azabicy-
by Ni(acac) in association with CuI in the absence of
2
clo[2.2.1]hept-5-en-3-one (3b): Yield: 211 mg (69%); yellow-
1
a ligand. A series of alkenyl derivatives of bridged ish gummy liquid; H NMR (300 MHz, CDCl ): d=0.87–
3
and cyclic lactams were obtained by this procedure. 0.91 (m, 3H), 1.32–1.37 (m, 4H), 1.54–1.59 (m, 2H), 2.25–
This procedure is also successful for coupling with 2.45 (m, 4H), 3.46 (s, 1H), 4.75 (d, J=1.5 Hz, 1H), 5.72 (d,
J=14.7 Hz, 1H), 6.39 (s, 1H), 6.66–6.69 (m, 1H), 6.88 (d,
acyclic amides and aryl halides. The significant feature
J=14.7 Hz, 1H), 6.93–6.96 (m, 1H), 7.17–7.35 (m, 5H);
of this protocol is alkenylation of Vince lactam via
1
3
2
C NMR (75 MHz, CDCl ): d=14.2, 22.5, 27.7, 29.1, 32.2,
C(sp )ÀN cross coupling, which has not been reported
3
53.6, 57.0, 61.2, 113.8, 123.2, 126.3, 128.0, 128.2 (2C), 128.3
so far and these products may possess much potential
in the pharmaceutical industry. The other advantages
are use of less expensive Ni/Cu catalyst, no use of
ligand and relatively good yield of products. We be-
lieve, this reaction will find useful applications in aca-
demia and industry.
(
3
2C), 128.7, 138.1, 138.9, 19.2, 139.7, 176.6; IR (neat): n=
018, 2958, 2931, 1701, 1647, 1215 cm ; anal. calcd. for
À1
C H NO: C 82.04, H 8.20, N 4.56; found: C 82.10, H 8.15,
2
1
25
N 4.60%.
(1S,4R)-2-[(E)-2-(Naphthalen-1-yl)vinyl]-2-azabicy-
clo[2.2.1]hept-5-en-3-one (3c): Yield: 209 mg (80%); brown
3
622
asc.wiley-vch.de
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2015, 357, 3617 – 3626

2
FULL PAPERS
Nickel–Copper-Catalyzed C(sp )ÀN Cross-Coupling of Cyclic and Bridged Amides
1
gummy liquid; H NMR (300 MHz, CDCl ): d=2.31 (d, J=
d=53.5, 57.0, 61.3, 107.9, 124.5, 126.7 (2C), 128.9 (2C),
131.8, 135.2, 139.1, 139.2, 176.7; IR (neat): n=3018, 2925,
3
8
4
7
4
.1 Hz, 1H), 2.42–2.46 (m, 1H), 3.49–3.51 (m, 1H), 4.88–
.90 (m, 1H), 6.65 (d, J=14.4 Hz, 1H), 6.69–6.73 (m, 1H),
.01–7.04 (m, 1H), 7.28 (d, J=14.4 Hz, 1H), 7.39–7.56 (m,
H), 7.72 (d, J=8.1 Hz, 1H), 7.83–7.86 (m, 1H), 8.07–8.10
m, 1H); C NMR (75 MHz, CDCl ): d=53.6, 57.0, 61.5,
05.9, 123.0, 123.7, 125.8, 125.9 (2C), 126.1, 127.1, 128.7,
À1
1708, 1645, 1382 cm ; HR-MS: m/z=268.0505, calcd. for
+
C H ClNO [M+Na] : 268.0500.
1
4
12
(1S,4R)-2-[(E)-2-Cyclohexylvinyl]-2-azabicyclo[2.2.1]-
13
(
hept-5-en-3-one (3i): Yield: 141 mg (65%); brownish gummy
3
1
1
1
3
liquid; H NMR (300 MHz, CDCl ): d=1.01–1.33 (m, 6H),
3
31.2, 133.7, 133.8, 139.0, 139.1, 176.7; IR (neat): n=3058,
012, 2923, 1716, 1635, 1365 cm ; HR-MS: m/z=284.0635,
1.63–1.72 (m, 4H), 1.93–1.98 (m, 1H), 2.18 (d, J=7.8 Hz,
1H), 2.29–2.32 (m, 1H), 3.38–3.40 (m, 1H), 4.56–4.57 (m,
1H), 4.91 (dd, J =14.4 Hz, J =7.2 Hz, 1H), 6.47 (d, J=
À1
+
calcd. for C H NO [M+Na] : 284.1046.
18
15
1
2
(
1S,4R)-2-(4-Methylstyryl)-2-azabicyclo[2.2.1]hept-5-en-3-
14.4 Hz, 1H), 6.61–6.64 (m, 1H), 6.87–6.89 (m, 1H);
1
3
one (3d): Yield: 191 mg (85%); colorless gummy liquid;
H NMR (300 MHz, CDCl ): d=2.34 (d, J=8.1 Hz, 1H),
.38 (s, 3H), 2.43–2.47 (m, 1H), 3.52–3.54 (m, 1H), 4.83–
.85 (m, 1H), 5.96 (d, J=15.0 Hz, 1H), 6.72–6.76 (m, 1H),
.00–7.03 (m, 1H), 7.15 (d, J=8.1 Hz, 2H), 7.26–7.33 (m,
H); C NMR (75 MHz, CDCl ): d=21.2, 53.6, 57.0, 61.2,
09.2, 123.3, 125.4 (2C), 129.5 (2C), 133.6. 136.1, 148.9,
39.2, 176.6; IR (neat): n=3014, 2950, 1712, 1647,
382 cm ; HR-MS: m/z=248.1046, calcd. for C H NO
C NMR (75 MHz, CDCl ): d=26.2 (2C), 33.8, 33.9 (2C),
3
1
38.7 (2C), 53.7, 57.3, 61.1, 115.8, 122.3, 138.7, 139.0, 176.5;
3
À1
2
4
7
3
1
1
1
IR (neat): n=2923, 2850, 1712, 1658, 1388 cm ; anal. calcd.
for C H NO: C 77.38, H 8.81, N 6.45; found: C 77.33, H
1
4
19
8.75, N 6.50%.
(1S,4R)-2-(Cyclohexylidenemethyl)-2-azabicyclo[2.2.1]-
13
3
hept-5-en-3-one (3j): Yield: 142 mg (70%); yellowish viscous
1
liquid; H NMR (300 MHz, CDCl ): d=1.67 (s, 6H), 2.07–
3
À1
+
2.18 (m, 5H), 2.42 (d, J=7.8 Hz, 1H), 3.35 (s, 1H), 4.31 (d,
J=1.8 Hz, 1H), 5.54 (s, 1H), 6.67–6.69 (m, 1H), 6.85–6.87
1
5
15
[
M+Na] : 248.0211.
(
1
3
1S,4R)-2-(2-Methylstyryl)-2-azabicyclo[2.2.1]hept-5-en-3-
(m, 1H); C NMR (75 MHz, CDCl ): d=26.5, 27.3, 28.1,
3
one (3e): Yield: 178 mg (79%); brownish gummy liquid;
28.9, 33.4, 53.6, 58.1, 66.5, 117.4, 136.9, 138.7, 139.7, 180.3;
IR (neat): n=3029, 2955, 1712, 1650, 1480,1335 cm ; anal.
1
À1
H NMR (300 MHz, CDCl ): d=2.28 (d, J=8.1 Hz, 1H),
3
2.34 (s, 3H), 2.37–2.41 (m, 1H), 3.46–3.48 (m, 1H), 4.79 (d,
calcd. for C H NO: C 76.81, H 8.43, N 6.89; found: C
1
3
17
J=1.8 Hz, 1H), 6.07 (d, J=14.7 Hz, 1H), 6.67–6.69 (m,
76.75, H 8.50, N 6.93%.
1
1
1
1
1
H), 6.95–6.98 (m, 1H), 7.10–7.17 (m, 4H), 7.36–7.39 (m,
(1S,4R)-2-[(1E,3Z)-Deca-1,3-dienyl]-2-azabicyclo[2.2.1]-
13
H); C NMR (125 MHz, CDCl ): d=20.0, 53.5, 56.8, 61.3,
hept-5-en-3-one (3k): Yield: 167 mg (68%); yellowish
3
1
06.8, 124.7, 124.8, 126.2, 126.4, 130.3, 134.6, 135.2, 138.9,
gummy liquid; H NMR (300 MHz, CDCl ): d=0.87–0.89
3
39.0, 176.5; IR (neat): n=3016, 2952, 1712, 1639,
(m, 3H), 1.22–1.27 (m, 8H), 2.02–2.13 (m, 2H), 2.20–2.25
(m, 1H), 2.30–2.34 (m, 1H), 3.40–3.42 (m, 1H), 4.62 (d, J=
1.8 Hz. 1H), 5.54–5.66 (m, 2H), 5.92–6.01 (m, 1H), 6.60–
À1
+
380 cm ; HR-MS: m/z=248.1050, calcd. for C H NO
1
5
15
[
M+Na] : 248.1046.
1S,4R)-2-(2-Fluorostyryl)-2-azabicyclo[2.2.1]hept-5-en-3-
one (3f): Yield: 185 mg (81%); brownish solid; mp 66–
1
3
(
6.65 (m, 2H), 6.87–6.92 (m, 1H); C NMR (75 MHz,
CDCl ): d=14.2, 22.8, 28.9, 29.6, 31.9, 32.9, 53.6, 57.1, 61.3,
3
1
7
1
1
28C; H NMR (300 MHz, CDCl ): d=2.29 (d, J=8.1 Hz,
110.3, 124.7, 127.8, 132.0, 138.9, 139.2, 176.5; IR (neat): n=
3
À1
H), 2.36–2.40 (m, 1H), 3.46–3.48 (m, 1H), 4.81–4.82 (m,
H), 6.02 (d, J=14.7 Hz, 1H), 6.65–6.69 (m, 1H), 6.95–7.14
3016, 2956, 2930, 1701, 1622, 1386 cm ; anal. calcd. for
C H NO: C 78.32, H 9.45, N 5.71; found: C 78.30, H 9.48,
1
6
23
(
m, 4H), 7.32 (d, J=14.7 Hz, 1H), 7.36–7.42 (m, 1H);
N 5.65%.
13
C NMR (75 MHz, CDCl ): d=53.5, 56.9, 61.1, 101.2 (d,
(E)-3-(2-Methylstyryl)oxazolidin-2-one (3l): Yield: 183 mg
(90%); white solid; mp 112–1168C; H NMR (500 MHz,
3
1
JC,F =4.5 Hz), 115.6 (d, JC,F =22.5 Hz), 124.3 (d, JC,F
=
3
3
1
1
.0 Hz), 124.5, 125.6 (d, JC,F =4.5 Hz), 126.0 (d, JC,F
=
CDCl ): d=2.34 (s, 3H), 3.87–3.90 (m, 2H), 4.53 (t, J=
3
.7 Hz), 127.4 (d, JC,F =8.2 Hz), 139.0 (d, JC,F =15.7 Hz),
59.7 (d, JC,F =236 Hz), 176.7; IR (neat): n=3020, 1712,
8.0 Hz, 2H), 5.91 (d, J=14.5 Hz, 1H), 7.14–7.18 (m, 3H),
1
3
7.29 (d, J=14.0 Hz, 1H), 7.42 (d, J=7.0 Hz, 1H); C NMR
À1
643, 1382 cm ; HR-MS: m/z=252.0795, calcd. for
(100 MHz, CDCl ): d=20.1, 42.7, 62.4, 108.9, 124.9, 125.1,
3
+
C H FNO [M+Na] : 252.0801.
126.5, 126.9, 130.4, 134.8, 134.9, 155.6; IR (neat): n=3018,
1
4
12
À1
(
1S,4R)-2-(2-Bromostyryl)-2-azabicyclo[2.2.1]hept-5-en-3-
2950, 1751, 1649, 1413 cm ; HR-MS: m/z=226.0588, calcd.
+
one (3g): Yield: 238 mg (82%); brownish solid; mp 102–
1
8
for C H NO [M+Na] : 226.0838.
1
2
13
2
1
058C; H NMR (400 MHz, CDCl ): d=2.31=(d, J=
(E)-3-[2-(Naphthalen-1-yl)vinyl]oxazolidin-2-one
Yield: 196 mg (82%); brownish gummy liquid; H NMR
(3m):
3
1
.4 Hz, 1H), 2.39–2.42 (m, 1H), 3.48–3.49 (m, 1H), 4.85 (d,
J=1.6 Hz, 1H), 6.22 (d, J=14.4 Hz, 1H), 6.67–6.69 (m,
(300 MHz, CDCl ): d=3.94–3.99 (m, 2H), 4.51–4.57 (m,
3
1
1
5
1
1
H), 6.98–7.03 (m, 2H), 7.20–7.26 (m, 2H), 7.45–7.50 (m,
2H), 6.45 (d, J=14.4 Hz, 1H), 7.38–7.58 (m, 4H), 7.76 (d,
J=7.1 Hz, 1H), 7.83–7.88 (m, 1H), 8.03–8.07 (m, 1H);
13
H), 7.50–7.53 (m, 1H); C NMR (100 MHz, CDCl ): d=
3
1
3
3.4, 56.8, 61.3, 107.8, 123.2, 126.8, 126.0, 127.7, 133.0, 138.9,
C NMR (100 MHz, CDCl ): d=42.8, 62.4, 108.1, 123.4,
3
39.2, 176.7; IR (neat): n=3064, 3018, 2995, 1716, 1635,
123.6, 125.9 (2C), 126.2, 127.5, 128.8, 131.2, 133.2, 133.9,
À1
+
375 cm ; HR-MS: m/z=312.0002, calcd. for C H BrNO
155.6; IR (neat): n=3049, 2922, 2852, 1759, 1645, 1418,
14
12
À1
+
[M+Na] : 311.9994.
1393 cm ; HR-MS: m/z=262.1020, calcd. for C H NO
15
13
2
(
1S,4R)-2-(4-Chlorostyryl)-2-azabicyclo[2.2.1]hept-5-en-3-
[M+Na] : 262.0838.
one (3h): Yield: 206 mg (84%); yellowish gummy liquid;
(E)-3-(2-Fluorostyryl)oxazolidin-2-one
184 mg (89%); brownish solid; mp 135–1408C; H NMR
(3n):
Yield:
1
1
H NMR (300 MHz, CDCl ): d=2.33 (d, J=8.1 Hz, 1H),
3
2
1
.40–2.44 (m, 1H), 3.51–3.52 (m, 1H), 4.80 (d, J=1.8 Hz,
H), 5.89 (d, J=14.7 Hz, 1H), 6.69–6.73 (m, 1H), 6.97–6.99
(300 MHz, CDCl ): d=3.82–3.87 (m, 2H), 4.47–4.52 (m,
3
2H), 5.85 (d, J=14.7 Hz, 1H), 6.98–7.18 (m, 3H), 7.37–7.42
13
13
(m, 1H), 7.23–7.29 (m, 5H); C NMR (125 MHz, CDCl ):
(m, 2H); C NMR (75 MHz, CDCl ): d=42.5, 62.5, 103.5
3
3
Adv. Synth. Catal. 2015, 357, 3617 – 3626
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
3623

Pintu Maity et al.
FULL PAPERS
À1
(
1
1
d, JC,F =3.7 Hz), 115.6 (d, JC,F =21.7 Hz), 123.7 (d, JC,F
2.7 Hz), 124.3 (d, JC,F =3.0 Hz), 125.8 (d, JC,F =5.2 Hz),
26.3 (d, JC,F =3.7 Hz), 127.9 (d, JC,F =8.2 Hz), 155.5, 159.7
=
1589, 1377 cm ; HR-MS: m/z=311.9994, calcd. for
+
C H BrNO [M+Na] : 312.0001.
(1S,4R)-2-[(E)-3,4-Dichlorostyryl]-2-azabicyclo[2.2.1]-
14
12
(
1
d, JC,F =246.7 Hz); IR (neat): n=3020, 2906, 1751, 1650,
hept-5-en-3-one (3t): Yield: 218 mg (78%); brownish solid;
À1
1
492 cm ; HR-MS: m/z=230.0673, calcd. for C H FNO
mp 150–1538C; H NMR (CDCl , 300 MHz): d=2.29 (d, J=
11
10
2
3
+
[M+Na] : 230.0588.
8.1 Hz, 1H), 2.36–2.39 (m, 1H), 3.46–3.48 (m, 1H), 4.74–
4.75 (m, 1H), 5.79 (d, J=14.7 Hz, 1H), 6.65–6.68 (m, 1H),
6.91–6.94 (m, 1H), 7.08–7.12 (m, 1H), 7.19–7.35 (m, 3H);
(
E)-1-(2-Fluorostyryl)pyrrolidin-2-one (3o): Yield: 170 mg
1
(83%); brownish solid; mp 85–898C; H NMR (400 MHz,
1
3
CDCl ): d=2.14–2.23 (m, 2H), 2.57 (t, J=8.4 Hz, 2H), 3.69
C NMR (CDCl , 75 MHz): d=53.4, 56.9, 61.3, 106.6, 124.5,
3
3
(
3
t, J=7.2 Hz, 2H), 6.02 (d, J=15.2 Hz, 1H), 7.01–7.17 (m,
H), 7.46–7.50 (m, 1H), 7.69 (d, J=15.2 Hz, 1H); C NMR
125.5, 127.1, 129.6, 130.6, 132.7, 137.0, 139.1, 176.6; IR
13
À1
(neat): n=3064, 2954, 1708, 1639, 1402 cm ; HR-MS: m/z=
+
(125 MHz, CDCl ): d=17.5, 31.3, 45.3, 104.1 (d, J
=
302.0110, calcd. for C H Cl NO [M+Na] : 302.0114.
3
C,F
14 11
2
3
1
1
2
.7 Hz), 115.6 (d, JC,F =12.5 Hz), 124.2 (d, JC,F =3.7 Hz),
24.3, 125.3 (d, JC,F =5.0 Hz), 126.2, 127.7 (d, JC,F =7.5 Hz),
(E)-3-(3-Bromostyryl)oxazolidin-2-one
216 mg (81%); brownish gummy liquid; H NMR (CDCl ,
300 MHz): d=3.80–3.85 (m, 2H), 4.47–4.53 (m, 2H), 5.67
(d, J=14.7 Hz, 1H), 7.12–7.17 (m, 1H), 7.21–7.46 (m, 3H);
(3v):
Yield:
1
3
59.8 (d, JC,F =246.2 Hz), 173.7; IR (neat): n=3012, 2962,
À1
926, 1689, 1641, 1489, 1402 cm HR-MS: m/z=228.0780,
;
+
13
calcd. for C H FNO [M+Na] : 228.0795.
C NMR (CDCl , 75 MHz): d=42.5, 62.4, 109.6, 122.9,
12
12
3
(
E)-1-[2-(Naphthalen-1-yl)vinyl]pyrrolidin-2-one
(3p):
124.0, 125.2, 128.6, 129.6, 130.3, 138.2, 155.6; IR (neat): n=
À1
Yield: 208 mg (88%); brownish solid; mp 120–1258C;
H NMR (300 MHz, CDCl ): d=2.17–2.27 (m, 2H), 2.56–
3018, 2852, 1760, 1652, 1409 cm ; HR-MS: m/z=289.9787,
1
+
calcd. for C H BrNO [M+Na] : 289.9791.
3
11 10
2
2
7
1
.62 (m, 2H), 3.77–3.82 (m, 2H), 6.58 (d, J=14.7 Hz, 1H),
.41–7.54 (m, 3H), 7.60–7.67 (m, 2H), 7.74 (d, J=8.4 Hz,
H), 7.82–7.87 (m, 1H), 8.05–8.08 (m, 1H); C NMR
(1S,4R)-2-(4-Methoxyphenyl)-2-azabicyclo[2.2.1]hept-5-
[13e]
en-3-one (4a):
Yield (X=I, Br): 189 mg (88%), 174 mg
13
1
(81%); H NMR (300 MHz, CDCl ): d=2.24–2.27 (m, 1H),
3
(
1
1
100 MHz, CDCl ): d=17.7, 31.4, 45.6, 108.7, 123.3, 123.7,
2.49 (d, J=8.1 Hz, 1H), 3.48–3.49 (m, 1H), 3.78 (s, 3H),
4.67 (d, J=2.1 Hz, 1H), 6.72 (s, 1H), 6.86–6.89 (m, 2H),
6.99–7.01 (m, 1H), 7.24–7.26 (m, 2H); C NMR (75 MHz,
3
25.7, 125.8, 125.9, 126.0, 127.4, 128.8, 131.3, 133.7, 133.9,
À1
13
73.6; IR (neat): n=3014, 2927, 1697, 1639, 1411, 1388 cm ;
+
HR-MS: m/z=260.1077, calcd. for C H NO [M+Na] :
CDCl ): d=22.8, 54.7, 55.6, 57.8, 65.5, 114.4 (2C), 120.9
16
15
3
2
60.1046.
E)-1-[2-(Naphthalen-1-yl)vinyl]azepan-2-one (3q): Yield:
(2C), 133.0, 138.6, 139.3, 156.5, 177.7.
(
(1S,4R)-2-p-Tolyl-2-azabicyclo[2.2.1]hept-5-en-3-one
1
[10b]
1
120 mg (45%); yellowish gummy liquid;
H NMR
(4b):
Yield: 181 mg (91%); H NMR (300 MHz, CDCl ):
3
(
300 MHz, CDCl ): d=1.25 (s, 2H), 1.84 (s, 4H), 2.72 (d,
d=2.21–2.25 (m, 1H), 2.29 (s, 3H), 2.43–2.46 (m. 1H), 3.46–
3.47 (m, 1H), 4.70 (q, J=1.8 Hz, 1H), 6.67–6.70 (m, 1H),
6.98–7.00 (m, 1H), 7.12 (d, J=8.4 Hz, 2H), 7.23–7.27 (m,
3
J=8.8 Hz, 2H), 3.86 (s, 2H), 6.70 (d, J=14.8 Hz, 1H), 7.43–
7
1
.52 (m, 2H), 7.60 (d, J=6.8 Hz, 1H), 7.73 (d, J=8.0 Hz,
H), 7.84 (d, J=8.4 Hz, 1H), 7.91 (d, J=14.8 Hz, 1H), 8.05
1
3
2H); C NMR (75 MHz, CDCl ): d=20.8, 54.7, 57.4, 64.8,
3
13
(d, J=7.6 Hz, 1H); C NMR (100 MHz, CDCl ): d=23.3,
118.8 (2C), 129.4 (2C), 133.5, 137.1, 138.4, 139.2, 177.4.
3
2
1
2
9.6, 29.7, 30.7, 43.2, 48.5, 107.6, 123.5, 123.7, 125.8, 126.9,
(1S,4R)-2-(Biphenyl-4-yl)-2-azabicyclo[2.2.1]hept-5-en-3-
[
13e]
27.2, 128.5, 128.8, 129.0, 134.1, 199.7; IR (neat): n=3346,
one (4c):
Yield (X=I, Br): 230 mg (87%), 206 mg (70%);
À1
1
926, 2854, 1724, 1692, 1627, 1445 cm ; anal. calcd. for
brownish solid; mp 140–1458C; H NMR (500 MHz,
C H NO: C 81.47, H 7.22, N 5.28; found: C 81.45, H 7.20,
CDCl ): d=2.29 (d, J=7.5 Hz, 1H), 2.50 (d, J=8.0 Hz, 1H),
1
8
19
3
N 5.34%.
3.53 (s, 1H), 4.81 (d, J=1.5 Hz, 1H), 6.73 (s, 1H), 7.05 (d,
J=4.5 Hz, 1H), 7.33 (t, J=7.5 Hz, 1H), 7.43 (t, J=7.5 Hz,
2H), 7.47 (d, J=8.5 Hz, 2H), 7.55–7.59 (m, 4H); C NMR
1-[(1E,3E)-3-Benzylideneoct-1-enyl]-4-methylquinolin-
1
3
2
(1H)-one (3r): Yield: 279 mg (78%); yellowish viscous
1
liquid; H NMR (300 MHz, CDCl ): d=0.90–0.95 (m, 3H),
(75 MHz, CDCl ): d=54.8, 57.3, 64.7, 118.9 (2C), 126.9
3
3
1
2
7
.37–1.46 (m, 4H), 1.76–1.81 (m, 2H), 2.49 (s, 3H), 2.60–
.65 (m, 2H), 6.53–6.74 (m, 4H), 7.24–7.40 (m, 6H), 7.49–
.58 (m, 2H), 7.70–7.73 (m, 1H); C NMR (75 MHz,
(2C), 127.2, 127.7 (2C), 128.9 (2C), 136.8, 138.7, 138.9,
139.1, 140.6, 177.4.
13
[9h]
1-Phenylpyrrolidin-2-one (4d):
Yield: 147 mg (91%);
1
CDCl ): d=14.2, 19.2, 22.6, 27.8, 29.0, 32.3, 116.1, 121.4,
H NMR (300 MHz, CDCl ): d=2.07–2.17 (m, 2H), 2.55–
3
3
1
1
21.6, 122.4, 122.9, 125.3, 127.2, 128.4 (2C), 128.9 (2C),
2.60 (m, 2H), 3.80–3.85 (m, 2H), 7.09–7.15 (m, 1H), 7.31–
7.37 (m, 2H), 7.57–7.61 (m, 2H); C NMR (75 MHz,
1
3
30.3, 133.4, 137.3, 137.8, 138.3, 139.9, 147.1, 162.1; IR
À1
(neat): n=3058, 2955, 2928, 2868, 1662, 1595, 1450 cm ;
CDCl ): d=18.1, 32.8, 48.8, 120.1 (2C), 124.5, 128.9 (2C),
3
+
HR-MS: m/z=358.2168, calcd. for C H NO [M+H] :
139.5, 174.4.
1-(4-Methoxyphenyl)pyrrolidin-2-one
172 mg (90%); H NMR (300 MHz, CDCl ): d=2.10–2.16
25
27
[
9h]
3
58.2165.
1S,4R)-2-[(E)-3-Bromostyryl]-2-azabicyclo[2.2.1]hept-5-
en-3-one (3s): Yield: 234 mg (84%); white solid; mp 135–
(4e):
Yield:
1
(
3
(m, 2H), 2.53–2.58 (m, 2H), 3.78 (s, 3H), 3.80 (d, J=6.9 Hz,
1
13
1
1
1
388C; H NMR (CDCl , 300 MHz): d=2.28 (d, J=8.1 Hz,
1H), 6.86–6.89 (m, 2H), 7.45–7.48 (m, 2H); C NMR
3
H), 2.35–2.39 (m, 1H), 3.45–3.47 (m, 1H), 4.74–4.76 (m,
H), 5.82 (d, J=14.7 Hz, 1H), 6.65–6.68 (m, 1H), 6.91–6.94
(75 MHz, CDCl ): d=18.1, 32.6, 49.3, 55.6, 114.2 (2C), 121.9
3
(2C), 132.8, 156.7, 174.0.
[
15]
(m, 1H), 7.08–7.13 (m, 1H), 7.18–7.26 (m, 3H), 7.43 (t, J=
N-Phenylbenzamide (5a):
Yield: 173 mg (88%);
H NMR (300 MHz, CDCl ): d=7.14 (t, J=7.5 Hz, 1H),
13
1
1
6
1
.8 Hz, 1H); C NMR (CDCl , 75 MHz): d=53.4, 56.9,
3
3
1.2, 107.5, 122.9, 123.9, 125.1, 128.3, 129.1, 130.2, 138.9,
39.0, 139.1, 176.6; IR (neat): n=3058, 2948, 1720, 1643,
7.32–7.38 (m, 2H), 7.42–7.55 (m, 3H), 7.64 (d, J=7.5 Hz,
1
3
2H), 7.85 (d, J=7.2 Hz, 2H), 8.01 (s, 1H); C NMR
3
624
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Adv. Synth. Catal. 2015, 357, 3617 – 3626

2
FULL PAPERS
Nickel–Copper-Catalyzed C(sp )ÀN Cross-Coupling of Cyclic and Bridged Amides
(
(
75 MHz, CDCl ): d=120.4 (2C), 124.7, 127.2 (2C), 128.9
2C), 129.2 (2C), 131.9, 135.1, 138.1, 166.0.
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Acknowledgements
We gratefully acknowledge financial support from DST,
Govt. of India, New Delhi with an award of the J. C Bose fel-
lowship to B.C.R. (Grant no. SR/S2/JCB-11/2008) and Indian
National Science Academy, New Delhi for an offer of INSA
Sr. Scientist position to B.C.R. Finally, P.M. and D.K. thank
CSIR, New Delhi for their Fellowships
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