Ni(0)-Catalyzed Synthesis of Polycyclic α,β-Unsaturated γ-Lactams via Intramolecular Carbonylative Cycloaddition of Yne-imines with CO

Article abstract of DOI:10.1055/s-0040-1707308

A Ni(0)-catalyzed intramolecular carbonylative cycloaddition between 1,5-yne-imines and carbon monoxide (CO) is disclosed. When Ni(CO) 3 PCy 3 was employed as a pre-catalyst, a variety of polycyclic α,β-unsaturated γ-lactams were prepared in up to 78% yield with 100% atom efficiency. Aza-nickelacycles, generated by the oxidative cyclization of yne-imines on the Ni(0) center, were experimentally confirmed as key intermediates. Moreover, diastereoselective transformations of the obtained products to afford highly substituted polycyclic γ-lactams with three contiguous carbon stereocenters are reported.

Full text of DOI:10.1055/s-0040-1707308

SYNLETT
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart
2
020, 31, A–E
cluster
A
Modern Nickel-Catalyzed Reactions
Synlett
K. Ashida et al.
Cluster
Ni(0)-Catalyzed Synthesis of Polycyclic ,-Unsaturated
-Lactams via Intramolecular Carbonylative Cycloaddition

of Yne-imines with CO
Keita Ashida
Ts
NTs
cat.
O
H
N
Yoichi Hoshimoto
Sensuke Ogoshi
R2
Ni(CO)3PCy3
up to 78% yield
100% atom-efficiency
R1
R1
+
CO
R2
•
•
Department of Applied Chemistry, Faculty of Engineering,
Osaka University, Suita, Osaka 565-0871, Japan
ogoshi@chem.eng.osaka-u.ac.jp
XRD-analysis of nickelacycle
Further derivatization of the products
O
S
Published as part of the Cluster to be replaced
Ts
P
O
Ni
Ts
N
H
N
H
O
N
Corresponding Author
SDe Mee npasaiulr kto meg oOe snghtoi o@s hf c iAh pe pm l i. e nd gC . oh se amk ai s- tur .ya ,c F. jap culty of Engineering, Osaka University, Suita, Osaka 565-0871, Japan
H
nBu
O
Received: 06.08.2020
Accepted after revision: 03.09.2020
Published online: 08.10.2020
molecular carbonylative cycloaddition of 1,5- or 1,6-ene-
imines to prepare polycyclic -lactams with 100% atom effi-
9
DOI: 10.1055/s-0040-1707308; Art ID: st-2020-k0429-c
ciency (Scheme 1A). Moreover, this Ni(0)-catalyzed intra-
molecular system was expanded to the corresponding en-
antioselective variant. As part of these studies, we de-
Abstract A Ni(0)-catalyzed intramolecular carbonylative cycloaddi-
tion between 1,5-yne-imines and carbon monoxide (CO) is disclosed.
When Ni(CO) PCy was employed as a pre-catalyst, a variety of polycy-
10
scribe
herein
a
Ni(0)-catalyzed
intramolecular
3
3
carbonylative cycloaddition of 1,5-yne-imines under a CO
atmosphere for the synthesis of polycyclic ,-unsaturated
clic ,-unsaturated -lactams were prepared in up to 78% yield with
00% atom efficiency. Aza-nickelacycles, generated by the oxidative cy-
1
clization of yne-imines on the Ni(0) center, were experimentally con-
firmed as key intermediates. Moreover, diastereoselective transforma-
tions of the obtained products to afford highly substituted polycyclic -
lactams with three contiguous carbon stereocenters are reported.

-lactams (Scheme 1B). Furthermore, we derivatized the
olefinic moieties in the produced ,-unsaturated -lact-
ams, which demonstrates the synthetic utility of the pres-
ent method for the synthesis of N-heterocyclic compounds
that bear multiple contiguous carbon stereocenters. The re-
sults of mechanistic studies that clarify the role of nickela-
cycles are also reported. It should be noted here that we
have already explored the corresponding carbonylative cy-
cloaddition in the presence of phenyl formate and NEt3,
which predominantly yielded isoquinoline derivatives via
Key words nickel-catalysis, carbonylative cycloaddition, ,-unsatu-
rated -lactams, aza-nickelacycle, yne-imines
The transition-metal-catalyzed [2+2+1] carbonylative
cycloaddition of ene-ynes with carbon monoxide (CO), also
1
known as the intramolecular Pauson–Khand reaction, is a
straightforward method for the construction of polycyclic
carbon frameworks. Carbonylative cycloaddition between
the NEt -catalyzed 6-exo-cyclization of the 1,5-yne-
imines.
3
2
11
yne-imines and CO are also of interest, as this reaction en-
ables the rapid construction of ,-unsaturated -lactam
cores, which are frequently found in biologically active
Initially, the optimal reaction conditions were explored
using 1,5-yne-imine 1a, which contains an N-tosyl (Ts)
group, and 0.5 atm of CO (Scheme 2). To avoid rapid satura-
tion of the reaction medium with CO, the experiments were
3
compounds. Nevertheless, this type of carbonylative cy-
cloaddition using C=N -components has been much less
studied due to the difficulties associated with the repeated
generation of the key aza-metalacycle intermediates under
cat. Ni(0)/L
CO gas
R
N
O
4
,5
a CO atmosphere.
Previous work (A)
Our research group has contributed to the development
of Ni(0)-catalyzed carbonylative cycloaddition reactions
based on the characteristic reactivity of Ni(0) to engage in
NR
R'
6
,7
cat. Ni(0)/L
CO gas
additional
derivatization
facile oxidative cyclization between two -components.
R
N
O
R
O
N
For example, we have reported a Ni(0)-catalyzed intermo-
lecular carbonylative cycloaddition between imines and
(B)
R'
R'
This work
alkynes, in which CO was generated in situ by treatment of
8
Scheme 1 Ni(0)-catalyzed intramolecular carbonylative cycloadditions
with (A) ene-imines or (B) yne-imines
phenyl formate with NEt . We have also disclosed a meth-
3
od for the direct use of CO gas for a Ni(0)-catalyzed intra-
©
2020. Thieme. All rights reserved. Synlett 2020, 31, A–E
Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany

B
Synlett
K. Ashida et al.
Cluster
NTs
Ts
N
afforded 2b and 2c in 67% and 78% yield, respectively. The
molecular structure of 2c was determined by single-crystal
X-ray diffraction (XRD) analysis. The reactions of 1d, which
contains a para-chlorine substituent, and 1e, which con-
tains a naphthyl skeleton, afforded 2d and 2e in 48% and
H
O
1
0 mol% Ni catalyst
+
CO
solvent, temp, 6 h
0
.5 atm
1
a
without stirring
2a
(
<7.0 equiv)
5
8% yield, respectively. In order to obtain 2f from 1f in 68%
Temp
°C)
Yield
(%)
(
Entry
Ni catalyst
Solvent
THF
yield, the reaction had to be carried out at 100 °C for 24 h.
The use of 1g, which bears an n-pentyl group at the alkyne
terminal, afforded 2g in 75% yield. In the case of 1h, which
contains a phenyl group at the alkyne terminal, -lactam 2h
was obtained in 72% yield when the reaction was carried
out at 100 °C for 24 h. However, when 1i and 1j were em-
ployed, a significant amount of the starting material re-
mained unreacted even after 24 h at 100 °C, and the forma-
tion of the corresponding -lactams (2i and 2j) was not
1
Ni(cod)2/PCy3
80
58
n
2
3
4
5
6
7
8
9
Ni(cod)2/P Bu3
THF
THF
THF
THF
80
80
80
80
80
80
80
40
36
13
<1
68
Ni(cod)2/PPh3
t
Ni(cod)2/P Bu3
Ni(CO)3PCy3
Ni(CO)3PCy3
Ni(CO)3PCy3
Ni(CO)3PCy3
Ni(CO)3PCy3
93 (<10)a
CPME
Toluene
DMF
2
confirmed. These results suggest that the η coordination of
83
the alkyne moieties to the Ni(0) center was prevented due
to steric hindrance, and thus the progress of oxidative cy-
clization on Ni(0) was hampered, which was experimental-
ly confirmed (Figures S7–11). When the N-Ts group was re-
placed with an N-diphenyl phosphinoyl group, a mixture of
unidentified products devoid of the target 2k was obtained.
The details of this reaction remain unclear.
<10
63
CPME
Scheme 2 Optimization of the reaction conditions for the Ni(0)-cata-
lyzed carbonylative cycloaddition between 1a and CO. All reactions
were carried out in a multiple autoclave reactor (V: 3.7 mL × 18 reac-
tors). 1a (0.10 mmol), Ni(cod) /PR (cod = 1,5-cyclooctadiene; R = Cy,
2
3
n
t
Bu, Ph, Bu) or Ni(CO) PCy (0.010 mmol), and solvent (1 mL) were
To gain insight into the reaction mechanism, a stoichio-
metric reaction of 1h with Ni(cod) /PCy was conducted in
3
3
mixed in each reactor, followed by pressurization with CO (0.5 atm) at
2
3
1
r.t. and heating. Yield was determined by H NMR spectroscopy using 2-
THF at room temperature, which furnished aza-nickelacycle
h in 80% isolated yield (Scheme 4A). The molecular struc-
ture of 3h was determined by single-crystal XRD analysis,
methoxynaphthalene as the internal standard. a The reaction was car-
ried out with stirring at 1350 rpm.
3
conducted without stirring.9,10 The reaction was examined
in THF at 80 °C using 10 mol% Ni(cod) and PCy , which re-
R3
R3
N
O
H
N
2
3
R2
10 mol% Ni(CO)3PCy3
CPME, 80 °C, 6 h
without stirring
R1
CO
R1
sulted in the formation of tricyclic ,-unsaturated -lac-
+
R2
n
t
0.5 atm
(<7.0 equiv)
tam 2a in 58% yield (entry 1), whereas P Bu , PPh , and P Bu
3
3
3
1
a–k
2a–k
furnished 2a in lower yield (entries 2–4). The use of
Ni(CO) PCy as the catalyst precursor furnished 2a in higher
3
3
Ts
N
Ts
Ts
O
O
O
yield (68%) than using Ni(cod) /PCy3 (entry 5). Thus, we
H
H
N
H
N
2
MeO
employed Ni(CO) PCy3 in the subsequent catalytic reac-
3
tions. Next, further optimizations of the reaction conditions
with respect to the solvent and reaction temperature were
carried out. Among the various solvents that we examined,
cyclopentyl methyl ether (CPME) afforded the best result
F
2
a: 75% (93%)
2b: 67%
2c: 78%
Ts
N
O
Ts
H
O
Ts
N
Ts
O
O
H
N
H
H
N
Cl
O
O
(
93% yield; entry 6). The reaction in toluene afforded 2a in
nC5H11
good yield (83%; entry 7), while the targeted reaction did
not proceed catalytically when DMF was used (entry 8). De-
creasing the reaction temperature to 40 °C resulted in a
lower reaction efficiency (63% yield; entry 9). We also con-
firmed that the catalytic reaction was hampered by stirring
the reaction solution (in parentheses of entry 6). Based on
these results, we concluded that the optimal conditions are
those shown in entry 6.
2f: 68%a
2
d: 48%
2e: 58%
2g: 75%
Ph
Ph
Ts
N
Ts
O
P
N
Ts
O
O
O
H
H
N
H
N
O
H
tBu
TMS
Ph
2h: 72%a
2i: (<1%)a
2j: (<1%)a
2k: (<1%)
We then explored the substrate scope of this catalytic
reaction using 1a–k under the optimal reaction conditions
Scheme 3 Ni(0)-catalyzed carbonylative cycloaddition of 1,5-yne-
imines. Compound 1a–k (0.10 mmol), Ni(CO) PCy (0.010 mmol), and
3
3
(
7
Scheme 3). The reaction between 1a and CO afforded 2a in
5% isolated yield. Substrates with meta-fluorine (1b) and
para-methoxy (1c) groups relative to the propargyl groups
CPME (1 mL) were mixed, followed by pressurization with CO (0.5 atm)
at r.t. and heating. Isolated yields are shown. NMR yield is given in pa-
rentheses. The reaction was performed at 100 °C for 24 h.
a
©
2020. Thieme. All rights reserved. Synlett 2020, 31, A–E

C
Synlett
K. Ashida et al.
Cluster
which revealed a set of enantiomers, i.e., (S ,R )- and (R ,S )-
To show the synthetic utility of the present Ni-catalyzed
reaction, diastereoselective transformations of 2a via the
derivatization of its olefinic moiety were examined
(Scheme 6). Hydrogenation of 2a in the presence of 3 mol%
Pd/C afforded 5a, which bears three contiguous carbon ste-
C
S
C
S
3
h, in the asymmetric unit of the single crystals; the molec-
ular structure of (S ,R )-3h is shown in Figure 1A. The chiral
C
S
sulfur centers are generated from the desymmetrization of
the achiral environment around the sulfur center via the in-
tramolecular coordination of the S=O moiety to the Ni cen-
ter (Ni–O1: 2.082(1) Å). We also confirmed that the coordi-
nated S=O group can be easily exchanged with another one
at room temperature in THF-d , as two resonances are ob-
8
served at 30.2 and 26.8 ppm in the 31P NMR spectrum of 3h,
probably showing the existence of diastereomers that are
generated via the coordination exchange between two S=O
ligands. These results are supported by the DFT calcula-
tions, i.e., the relative Gibbs free energy of (S ,S )-3h with
C
S
–
1
respect to (S ,R )-3h is estimated as –0.4 kcal mol and the
C
S
activation energy barrier for the generation of (S ,S )-3h
C
S
–1
from (S ,R )-3h is +13.7 kcal mol (Figure S21). The reac-
C
S
tion between 3h and CO (3.0 atm) in THF-d quantitatively
8
afforded 2h and Ni(CO) PCy3 (Scheme 4B). These results
3
suggest the formation of an intermediary aza-nickelacycle
in the reaction of 1h under the applied reaction conditions.
To gain further information regarding the reaction between
3
h and CO, we monitored the reaction of 3h with CNCy,
1
2
which is isoelectronic with CO. Treatment of 3h with an
equimolar amount of CNCy resulted in the generation of 4h,
in which the tricyclic ,-unsaturated amidine coordinates
to Ni(0) (Scheme 4C). After the addition of another equiva-
lent of CNCy and recrystallization, 4h was isolated in 82%
yield. The molecular structure of 4h was determined by sin-
gle-crystal XRD analysis (Figure 1B).
O
O
p-Tol
*
S
Ni(cod)
PCy
2
(1.0 equiv)
(1.0 equiv)
H
Figure 1 Molecular structures of (S ,R )-3h and 4h with thermal ellip-
soids at 30% probability; only selected H atoms are shown and cyclo-
hexyl groups are omitted for clarity. Selected bond lengths [Å] of
N
*
C
S
Ni
3
(A)
PCy
3
1
h
THF, rt, 1 h
Ph
(
1
S ,R )-3h: Ni–O1, 2.082(1); Ni–N1, 1.893(2); Ni–C1, 1.931(2); S1–O2,
.490(1); S1–O2, 1.434(2); 4h: Ni–C1, 1.978(2); Ni–C2, 1.926(2); Ni–
C S
3h: 80%
CNCy
Ts
C5, 1.819(3); C1–C2, 1.451(3); C5–N3, 1.163(4); C4–N1, 1.439(3); C4–
N2, 1.268(3).
1
) CNCy (1.0 equiv)
Cy
3
P
H
2
h
Ni
(C)
(B)
CO (3 atm)
THF-d
THF-d , rt, 30 min
8
N
N
+
Cy
8
2) CNCy (1.0 equiv)
rt, 30 min
Ni(CO)
3
PCy
3
Ph
h: 82%
rt, 30 min
quanta
O
O
4
p-Tol
S
N
R1
H
Scheme 4 Isolation and reactivity of 3h. Isolated yield of the products
Ni
PCy3
R2
a
is given. The yield was confirmed by NMR analyses.
O
O
3
p-Tol
Based on the aforementioned results, this Ni(0)-cata-
lyzed carbonylative [2+2+1] cycloaddition can be expected
to proceed via the mechanism shown in Scheme 5. Replace-
ment of the CO ligands in Ni(CO) PCy with yne-imine 1
S
N
yne-imine
PCy3
R2
R1
CO
1
Ni
Ni(CO) PCy3
3
3
3
CO
2
2
generates (η :η -1)Ni(PCy ), which is then subject to an oxi-
CO
3
Cy3P
Ts
N
Ni
dative cyclization to give aza-nickelacycle 3. The reaction of
H
O
H
Ts
R1
N
O
CO with 3 and the subsequent reductive elimination afford
R1
R2
R2
2
(
η -2)Ni(CO)(PCy ) (4′). Finally, ligand substitution between
3
2
1
4'
4
′ and 1 occurs to furnish 2 under concomitant regenera-
2
2
Scheme 5 A plausible mechanism for the Ni(0)-catalyzed [2+2+1] car-
bonylative cycloaddition of 1 with CO
tion of (η :η -1)Ni(PCy ).
3
©
2020. Thieme. All rights reserved. Synlett 2020, 31, A–E

D
Synlett
K. Ashida et al.
Cluster
reogenic centers, in 94% yield (Scheme 6A). The conjugate
References and Notes
n
addition of [ Bu Cu]Li to 2a proceeded to furnish a diaste-
2
(
1) (a) Khand, I. U.; Knox, G. R.; Pauson, P. L.; Watts, W. E.; Foreman,
M. I. J. Chem. Soc., Perkin Trans. 1 1973, 977. (b) Exon, C.;
Magnus, P. J. Am. Chem. Soc. 1983, 105, 2477. (c) Shibata, T. Adv.
Synth. Catal. 2006, 348, 2328. (d) The Pauson–Khand Reaction:
Scope, Variations and Applications; Torres, R. R., Ed.; Wiley-VCH:
Weinheim, 2012.
reomeric mixture of 6a (86% yield; d.r. 80:20), which bears
quaternary carbon centers at the C4 positions (Scheme 6B).
A Diels–Alder reaction with Danishefsky’s diene successful-
ly expanded the fused-ring system of 2a to 7a (46% yield),
and two contiguous quaternary carbon centers were con-
structed (Scheme 6C). The molecular structure of 7a was
determined by a single-crystal XRD analysis (Figure S20).
(
2) For selected examples of the application of the Pauson–Khand
reaction in the total synthesis of complex natural products, see:
(
a) Castro, J.; Sörensen, H.; Riera, A.; Morin, C.; Moyano, A.;
Pericàs, M. A.; Greene, A. E. J. Am. Chem. Soc. 1990, 112, 9388.
b) Jamison, T. F.; Shambayati, S.; Crowe, W. E.; Schreiber, S. L. J.
Ts
3
5
mol% Pd/C
atm H2
H
O
H
N
(
(
A)
Am. Chem. Soc. 1994, 116, 5505. (c) Jamison, T. F.; Shambayati,
S.; Crowe, W. E.; Schreiber, S. L. J. Am. Chem. Soc. 1997, 119,
4353. (d) Brummond, K. M.; Lu, J. J. Am. Chem. Soc. 1999, 121,
EtOAc, 60 °C, 24 h
H
5a: 94%
5
087. (e) Cassayre, J.; Zard, S. Z. J. Am. Chem. Soc. 1999, 121,
n
1
2
) [ Bu2Cu]Li (1.5 equiv)
THF, –30 °C, 1 h
then rt, 3 h
Ts
Ts
N
6072. (f) Madu, C. E.; Lovely, C. J. Org. Lett. 2007, 9, 4697.
(g) Pallerla, M. K.; Fox, J. M. Org. Lett. 2007, 9, 5625. (h) Hirose,
T.; Miyakoshi, N.; Mukai, C. J. Org. Chem. 2008, 73, 1061.
(i) Nakayama, A.; Kogure, N.; Kitajima, M.; Takayama, H. Angew.
Chem. Int. Ed. 2011, 50, 8025. (j) Jøgensen, L.; McKerrall, S. J.;
Kuttruff, C. A.; Ungeheuer, F.; Felding, J.; Baran, P. S. Science
2013, 341, 878. (k) Chuang, K. V.; Xu, C.; Reisman, S. E. Science
2016, 353, 912. (l) Liang, X.-T.; Chen, J.-H.; Yang, Z. J. Am. Chem.
Soc. 2020, 142, 8116.
H
O
H
O
N
H
H
(
(
B)
C)
+
2a
) 1 M NH4Cl (aq)
rt, 1 h
nBu
nBu
6
a: 86%, d.r. 80:20
Ts
N
H
O
OMe
Danishefsky's diene
2 equiv)
(
toluene, reflux, 72 h
OTMS
Danishefsky's
diene
(3) For selected examples of biologically active compounds includ-
ing ,-unsaturated -lactam cores, see: (a) Koehn, F. E.;
McConnell, O. J.; Longley, R. E.; Sennett, S. H.; Reed, J. K. J. Med.
Chem. 1994, 37, 3181. (b) Shiraki, R.; Sumino, A.; Tadano, K.;
Ogawa, S. J. Org. Chem. 1996, 61, 2845. (c) Mandal, A. K.; Hines,
J.; Kuramochi, K.; Crews, C. M. Bioorg. Med. Chem. Lett. 2005, 15,
O
7
a: 46%
Scheme 6 Diastereoselective transformations of 2a. Relative stereo-
chemistry is shown for 5a–7a. Yield of the isolated products is shown.
4
043. (d) Micheli, F.; Pasquarello, A.; Tedesco, G.; Hamprecht, D.;
In conclusion, we have developed a Ni(0)-catalyzed
2+2+1] carbonylative cycloaddition of yne-imines with CO
Bonanomi, G.; Checchia, A.; Jaxa-Chamiec, A.; Damiani, F.;
Davalli, S.; Donati, D.; Gallotti, C.; Petrone, M.; Rinaldi, M.; Riley,
G.; Terreni, S.; Wood, M. Bioorg. Med. Chem. Lett. 2006, 16, 3906.
[
to afford polycyclic ,-unsaturated -lactam derivatives
with 100% atom efficiency.13 The isolation of an aza-nickel-
acycle and investigation of its reactivity revealed that the
present Ni(0)-catalyzed reaction proceeds via aza-nickela-
cycle intermediates. The obtained products can be diastereo-
selectively transformed into compounds with consecutive
quaternary carbon centers, which demonstrates the syn-
thetic utility of the present method.
(e) Feng, Z.; Chu, F.; Guo, Z.; Sun, P. Bioorg. Med. Chem. Lett.
2009, 19, 2270. (f) Zhu, G.-Y.; Chen, G.; Liu, L.; Bai, L.-P.; Jiang,
Z.-H. J. Nat. Prod. 2014, 77, 983. (g) Yang, X.-R.; Tanaka, N.; Tsuji,
D.; Lu, F.-L.; Yan, X.-J.; Itoh, K.; Li, D.-P.; Kashiwada, Y. Tetrahe-
dron 2019, 75, 130779.
(
(
4) For examples of the synthesis of polycyclic ,-unsaturated -
lactams via transition-metal-catalyzed intramolecular carbon-
ylative cycloaddition reactions, see: (a) Chatani, N.; Morimoto,
T.; Kamitani, A.; Fukumoto, Y.; Murai, S. J. Organomet. Chem.
1
999, 579, 177. (b) Mukai, C.; Yoshida, T.; Sorimachi, M.; Odani,
Funding Information
A. Org. Lett. 2006, 8, 83.
5) (a) Chatani, N.; Tobisu, M.; Asaumi, T.; Murai, S. Synthesis 2000,
This work was supported by Grant-in-Aid for Scientific Research from
the Japan Society for the Promotion of Science (JSPS KAKENHI Grant
Number; 15H05803 (S.O.) and 18K14219 (Y.H.)). K.A. expresses his
9
(
4
25. (b) Göbel, A.; Imhof, W. Chem. Commun. 2001, 593.
c) Kang, S.-K.; Kim, K.-J.; Hong, Y.-T. Angew. Chem. Int. Ed. 2002,
1, 1584. (d) McLaughlin, M.; Takahashi, M.; Micalizio, G. C.
special thanks for a Grant-in-Aid for JSPS Fellows.
J
apa
n
S
ociety forth
e
Pro
m
otio
n
o
f
Science(1
5
H
0
5
8
0
3)Japan Society forth
e
Pro
m
oti
o
n
o
f
S
cience(1
8
K
1
4
2
1
9)
Angew. Chem. Int. Ed. 2007, 46, 3912. (e) Iwata, T.; Inagaki, F.;
Mukai, C. Angew. Chem. Int. Ed. 2013, 52, 11138. (f) Fukuyama,
T.; Okada, T.; Nakashima, N.; Ryu, I. Helv. Chim. Acta 2019, 102,
e1900186.
Supporting Information
(
6) For reviews on nickel-catalyzed reactions via (hetero)nickelacy-
cle intermediates, see: (a) Montgomery, J. Angew. Chem. Int. Ed.
Supporting information for this article is available online at
https://doi.org/10.1055/s-0040-1707308.
S
u
p
p
ortingInform ati
o
nS
u
p
p
ortingInformati
o
n
2
004, 43, 3890. (b) Moslin, R. M.; Miller-Moslin, K.; Jamison, T.
F. Chem. Commun. 2007, 4441. (c) Ng, S.-S.; Ho, C.-Y.; Schleicher,
K. D.; Jamison, T. F. Pure Appl. Chem. 2008, 80, 929. (d) Tanaka,
K.; Tajima, Y. Eur. J. Org. Chem. 2012, 3715. (e) Montgomery, J.
Organonickel Chemistry, In Organometallics in Synthesis: Fourth
Manual; Lipshutz, B. H., Ed.; Wiley: Hoboken, 2013, 319–428.
©
2020. Thieme. All rights reserved. Synlett 2020, 31, A–E

E
Synlett
K. Ashida et al.
Cluster
(f) Tasker, S. Z.; Standley, E. A.; Jamison, T. F. Nature 2014, 509,
used. To a solution of Ni(CO) PCy3 (4.2 mg, 0.010 mmol) in
3
2
99. (g) Ogoshi, S.; Hoshimoto, Y.; Ohashi, M.; Kumar, R. Reac-
CPME (1.0 mL) was added 1 (0.100 mmol) at r.t. The mixture
was transferred into a 2 mL vial, followed by pressurization
with CO (0.5 atm, < 7.0 equiv). After heating at 80 °C for 6 h
without stirring, the resulting mixture was quenched with
MeOH. After filtration through silica gel (eluted with MeOH), all
volatiles were removed under reduced pressure. The residue
was purified by flash column chromatography (silica gel, 10%
then 20–60% EtOAc/hexane) and subsequent recrystallization
tions via Nickelacycles, In Nickel Catalysis in Organic Synthesis:
Methods and Reactions; Ogoshi, S., Ed.; Wiley-VCH; Weinheim,
2020; 3–67.
(
7) For selected studies on aza-nickelacycles derived from imines
and unsaturated compounds, see: (a) Ogoshi, S.; Ikeda, H.;
Kurosawa, H. Angew. Chem. Int. Ed. 2007, 46, 4930. (b) Ogoshi,
S.; Ikeda, H.; Kurosawa, H. Pure Appl. Chem. 2008, 80, 1115.
(c) Ohashi, M.; Kishizaki, O.; Ikeda, H.; Ogoshi, S. J. Am. Chem.
(CHCl /pentane, –20 °C) or recycling HPLC, to afford ,-unsatu-
3
Soc. 2009, 131, 9160. (d) Hoshimoto, Y.; Ohata, T.; Ohashi, M.;
Ogoshi, S. Chem. Eur. J. 2014, 20, 4105. (e) Ohashi, M.;
Hoshimoto, Y.; Ogoshi, S. Dalton Trans. 2015, 12060.
rated -lactams 2. 3-Methyl-1-tosyl-4,8b-dihydroindeno[1,2-
b]pyrrol-2(1H)-one (2a): Obtained by following the general
procedure using 1a (31.4 mg, 0.100 mmol). The residue was
purified by silica gel column chromatography (10% then 40%
(
f) Shirataki, H.; Ono, T.; Ohashi, M.; Ogoshi, S. Org. Lett. 2019,
1, 851.
2
EtOAc/hexane) and recrystallization from CHCl /pentane at –20
3
(
(
8) Hoshimoto, Y.; Ohata, T.; Sasaoka, Y.; Ohashi, M.; Ogoshi, S.
J. Am. Chem. Soc. 2014, 136, 15877.
9) Hoshimoto, Y.; Ashida, K.; Sasaoka, Y.; Kumar, R.; Kamikawa, K.;
Verdaguer, X.; Riera, A.; Ohashi, M.; Ogoshi, S. Angew. Chem. Int.
Ed. 2017, 56, 8206.
°C to afford 2a as a white solid in 75% yield (25.6 mg, 0.0754
1
mmol); mp 144–148 °C. H NMR (CDCl , 400 MHz):  = 8.07 (d,
3
J = 7.2 Hz, 1 H, Ar-H), 8.01 (d, J = 8.4 Hz, 2 H, Ar-H), 7.37–7.26
(m, 5 H, Ar-H, overlapped with solvent peak), 5.87 (s, 1 H,
CHNTs), 3.75 (d, J = 18.0 Hz, 1 H, CCH C), 3.66 (d, J = 18.0 Hz, 1 H,
2
1
3
1
(
10) Ashida, K.; Hoshimoto, Y.; Tohnai, N.; Scott, D. E.; Ohashi, M.;
CCH C), 2.43 (s, 3 H, Ts-CH ), 1.79 (s, 3 H, C(O)CCH ). C{ H}
2
3
3
Imaizumi, H.; Tsuchiya, Y.; Ogoshi, S. J. Am. Chem. Soc. 2020,
NMR (CDCl , 100 MHz):  = 171.8, 161.8, 145.1, 142.8, 137.9,
3
1
42, 1594.
135.6, 129.8, 129.1, 128.7, 128.2, 126.5, 126.2, 125.2, 67.7, 31.2,
(
11) Hoshimoto, Y.; Nishimura, C.; Sasaoka, Y.; Kumar, R.; Ogoshi, S.
Bull. Chem. Soc. Jpn. 2020, 93, 182.
21.8, 9.2. HRMS (CI): m/z [M + H]+ calcd for C19H18NO S:
3
340.1007; found: 340.1013. Preparation of 3h: To a solution of
(
12) For studies on Ni(0)-mediated or -catalyzed cycloaddition reac-
tions of ene-ynes with isocyanides, see: (a) Tamao, K.;
Kobayashi, K.; Ito, Y. J. Am. Chem. Soc. 1988, 110, 1286.
Ni(cod) (27.5 mg, 0.100 mmol) and PCy (28.0 mg, 0.100 mmol)
2
3
in THF (3.0 mL) was added 1h (37.4 mg, 0.100 mmol) at r.t. The
reaction solution was stirred vigorously for 1 h to confirm the
precipitation of reddish purple solids. After removal of all vola-
tiles, the resulting solids were washed with cold THF/hexane to
afford aza-nickelacycle 3h as a reddish-purple solid in 80% yield
(57.2 mg, 0.0803 mmol). A single crystal of 3h suitable for X-ray
diffraction analysis was obtained by slow diffusion of pentane
into a THF solution of 3h. Complex 3h was almost insoluble in
the common solvents. While two distinctive resonances, which
can be derived from the existence of diastereomeric isomers
such as (S ,R )- and (S ,S )-3h as well as (R ,R )- and (R ,S )-3h
(b) Zhang, M.; Buchwald, S. L. J. Org. Chem. 1996, 61, 4498.
(
13) All manipulations were conducted under a nitrogen atmo-
1
13
sphere using standard Schlenk or dry-box techniques. H, C,
1
9
31
F, and P NMR spectra were recorded with Bruker AVANCE III
1
4
00 spectrometers at 25 °C. The chemical shifts in the H NMR
spectra were recorded relative to residual protonated solvent
(
C D H ( = 7.16 ppm) or CHCl ( = 7.26 ppm)). The chemical
6 5 3
shifts in the 13C NMR spectra were recorded relative to deuter-
ated solvent (CDCl ( = 77.16 ppm)). Assignment of the reso-
3
C
S
C
S
C
S
C
S
1
13
1
1
nances in the H and C NMR spectra was based on H- H COSY,
HMQC, and HMBC experiments. Medium-pressure column
chromatography was carried out with a Biotage Flash Purifica-
tion System Isolera, equipped with a 254 nm UV detector. High-
resolution mass spectrometry (HRMS) and elemental analyses
were performed at the Instrumental Analysis Centre, Faculty of
Engineering, Osaka University. Melting points were determined
with a Stanford Research Systems MPA100 OptiMelt Automated
Melting-Point System. X-ray crystal data were collected with
Rigaku XtaLAB Synergy equipped with the HyPix-6000HE
detector. Catalytic reactions were carried out by using multiple
autoclave reactors (3.7 mL × 18 reactors, EYELA, HIP-7518).
Caution: Carbon monoxide is toxic and may react with Ni(0) to
(see Figure S21), were observed when 3h was dispersed in THF-
d , the observed resonances could not be fully assigned due to
8
its complexity. 1H NMR (400 MHz, THF-d ):  = 9.05 (brs, 2 H,
8
Ar-H, minor), 7.89 (brs, 2 H, Ar-H, major), 7.57 (brs, 2 H, Ar-H,
minor), 7.31–6.82 (m, major + minor), 6.52 (brs, 1 H, Ar-H,
major), 6.10 (s, 1 H, CHNTs, major), 4.78 (s, 1 H, CHNTs, minor),
3.19 (d, J = 17.6 Hz, 1 H, CCH C, major), 2.86 (d, J = 17.6 Hz, 1 H,
2
CCH C, minor), 2.75 (d, J = 17.6 Hz, 1 H, CCH C, major), 2.63 (d,
2
2
J = 17.6 Hz, 1 H, CCH C, minor), 2.49–2.16 (m, major + minor),
2
1.73–1.62 (m, major + minor + THF), 1.26–0.87 (m, major +
minor). 13C{ H} NMR (100 MHz, THF-d ):  = 144.0, 128.9, 128.0,
1
8
127.4, 126.3, 124.2, 123.4, 31.4, 29.9, 29.5, 27.4, 26.9, 26.2, 25.9,
25.4, 20.4. Several peaks were not observed due to the low con-
centration. 31P{ H} NMR (162 MHz, THF-d ):  = 30.2 (minor),
1
afford Ni(CO) . All experiments in this manuscript must be
4
8
carried out under well-ventilated conditions.
26.8 (major). Anal. Calcd for C41H52NNiO PS: C, 69.11; H, 7.36;
2
Ni(0)-Catalyzed [2+2+1] Carbonylative Cycloadditions of 1
with CO; General Procedure
A multiple reactor (3.7 mL × 18 reactors, EYELA, HIP-7518) was
N, 1.97. Found: C, 68.15; H, 7.41; N, 2.25. Accurate elemental
analyses of 3h was precluded by extreme air or thermal sensi-
tivity and/or systematic problems.
©
2020. Thieme. All rights reserved. Synlett 2020, 31, A–E