Ni-Al Bimetallic Catalyzed Enantioselective Cycloaddition of Cyclopropyl Carboxamide with Alkyne

Article abstract of DOI:10.1021/jacs.7b09947

A Ni-Al bimetallic catalyzed enantioselective cycloaddition reaction of cyclopropyl carboxamides with alkynes has been developed. A series of cyclopentenyl carboxamides were obtained in up to 99% yield and 94% ee. The bifunctional-ligand-enabled bimetallic catalysis proved to be an efficient strategy for the C-C bond cleavage of unreactive cyclopropanes.

Full text of DOI:10.1021/jacs.7b09947

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Communication
Ni-Al Bimetallic Catalyzed Enantioselective
Cycloaddition of Cyclopropyl Carboxamide with Alkyne
Qi-Sheng Liu, De-Yin Wang, Zhi-Jun Yang, Yu-Xin Luan,
Jin-Fei Yang, Jiang-Fei Li, You-Ge Pu, and Mengchun Ye
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.7b09947 • Publication Date (Web): 05 Dec 2017
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Ni-Al Bimetallic Catalyzed Enantioselective Cycloaddition of
Cyclopropyl Carboxamide with Alkyne
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Qi-Sheng Liu1†, De-Yin Wang1†, Zhi-Jun Yang1, Yu-Xin Luan1, Jin-Fei Yang1, Jiang-Fei Li1, You-Ge
Pu1, Mengchun Ye1,2*
1State Key Laboratory and Institute of Elemento-Organic Chemistry, College of Chemistry, Nankai University, Tianjin
300071, China.
2Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University, Tianjin 300071, China.
Supporting Information Placeholder
Scheme 1. Transition-Metal-Catalyzed Cycloaddition of
ABSTRACT: A Ni-Al bimetallic catalyzed enantioselective
Cyclopropane with π-unsaturated compound
cycloaddition reaction of cyclopropyl carboxamides with alkynes
has been developed. A series of cyclopentenyl carboxamides were
obtained in up to 99% yield and 94% ee. The bifunctional-ligand-
enabled bimetallic catalysis proved to be an efficient strategy for
the C–C bond cleavage of unreactive cyclopropanes.
Transition-metal-catalyzed cycloaddition of cyclopropane with
π-unsaturated compound has emerged as a powerful tool for the
construction of cyclic structural units during the past decades.1,2
Among various functionalized cyclopropanes used in cycloaddi-
tion reactions, cyclopropyl carboxylates, including carboxylic
acids, esters and amides, are one of the most attractive classes of
substrates because carboxylate groups are not only readily availa-
ble, but also participate in versatile transformations in organic
synthesis. However, their cycloaddition reaction still remains an
elusive challenge. Different from highly-strained cyclopropanes
bearing fused π-unsaturation (cyclopropene3 and alkylidenecyclo-
propane4), less-strained cyclopropanes bearing adjacent π-
unsaturation (vinylcyclopropane5 and cyclopropanes containing
polar π-bonds6-9) prove quite inert in the oxidative addition to
transition metal. Wender and co-workers in 1995 revealed for the
first time that the formation of an allyl-metal intermediate greatly
facilitated the oxidative addition process (Scheme 1a, strategy
(i)).5a Later, Montgomery group and Ogoshi group independently
found that the formation of an oxa(aza)-nickelacycle intermediate
also greatly improved the oxidative addition and the subsequent
cycloaddition with an activated π-compound (strategy (ii)).10–14
However, in sharp contrast, cyclopropyl carboxylates could gen-
erate neither allyl-metal nor oxa(aza)-nickelacycle intermediates,
so that a high activation energy barrier has to be overcome for the
formation of unstable metallocyclobutane species. Herein, we
report a Ni-Al bimetallic synergism to facilitate the cycloaddition
reaction of cyclopropyl carboxamide with alkyne for the first
time, in which the ligand-Ni-Al combination probably played a
triple role: activating cyclopropane substrate, directing nickel
oxidative addition and stabilizing the in-situ formed nickellacycle
(Scheme 1b). In addition, a successful enantioselective control of
this reaction was also achieved by the use of taddol-derived chiral
phosphine oxide ligand with up to 94% ee.
We commenced our studies by treatment of cyclopropyl car-
boxamide (1a) with oct-4-yne 2a under 10 mol% of Ni(cod)2 as
the catalyst and 1.0 equivalent of AlMe3 as the promoter. Initially,
various arylphosphines, alkylphosphines and carbenes were em-
ployed to promote the cycloaddition reaction under similar condi-
tions to Ogoshi’s reaction,13 while no desired product was detect-
ed under varying temperatures. Then we envisioned that a bifunc-
tional ligand could be used to simultaneously bind nickel catalyst
and Lewis acid promoter to accelerate the oxidative addition of
nickel to cyclopropane. Phenolic (L1) and naphtholic phosphine
(L2 and L3), were firstly selected to be tested (entries 1–3). Grati-
fyingly, trace amounts of desired product (3a) were indeed detect-
ed by GC analysis for L1 and L2, and even 8% yield was ob-
served for O-protected ligand L3. Inspired by Cramer’s and oth-
ers’ reports on unique bifunctional secondary-phosphine-oxide
(SPO) ligand,15,16 we chose various trivalent phosphorus com-
pounds such as Ph2POMe, Ph2PCl and Ph2P(O)H for further op-
timization (entries 4–6). Results showed that Ph2POMe was inef-
ficient for this reaction, whereas Ph2PCl slightly improved the
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yield to 11%. Most delightedly, Ph2P(O)H was found to be an
excellent ligand, affording 3a in 44% yield.
Encouraged by this result, we then examined a wide range of
reaction parameters using Ph2P(O)H as the ligand (see the Sup-
porting Information). The reaction was found to be highly de-
pendent on loadings of the ligand. Increasing loadings of
Ph2P(O)H to 20 mol% and 30 mol%, the yield of 3a was elevated
significantly to 74% and 81%, respectively (entries 7 and 8). Us-
ing additional PPh3 (10 mol%) further enhanced the yield to 86%
(entry 9). Under the combined-ligand conditions, tri-
phenylphosphine oxide was completely inefficient (entry 10),
suggesting secondary phosphine oxide structure was critical to the
reaction. Other phosphine oxides did not give better results (en-
tries 11–16).
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Table 1. Ligand Effects
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With the above optimized reaction conditions in hand, we first
explored an array of alkynes to test the generality of the reaction
(Table 2). Various symmetrical alkynes bearing dialkyl (3a–3d),
di(hetero)aryl (3e–3o) and bistrimethylsilyl (3p) were well toler-
ated, providing the corresponding cyclopentene in 44% to 93%
yield. Various unsymmetrical alkynes (3q–3t) were also compati-
ble with this reaction, but providing a mixture of regioisomers
with varying ratios from 53:47 to 86:14. Amides bearing different
substituents on N atom (4a–4e) did not have big influence on the
current reaction. Notably, the Weinreb amide bearing a reactive
N-O bond afforded a desmethoxy product in 52% yield (4f),
whereas mono-substituted amide with a proton on the N atom was
not tolerated in this reaction. In addition, a phenyl group in the
cyclopropyl ring led to a different regioselective product (4g),
suggesting that the substrate could play a donor-acceptor-
cyclopropane role in this case. Instead, the methyl group still pro-
vided the same regioselective product (4h), and an epimerized
isomer from the enolization of the corresponding nickelacycle
was not observed.13 But unfortunately, the current method was not
applicable to cyclopropyl carboxylic ester, likely owing to its
weaker interaction with AlMe3.
aReaction conditions: 1a (0.2 mmol), 2a (0.6 mmol), mesitylene
(2 mL), under N2 for 24 h; GC yield using n-dodecane as the in-
ternal standard. bPh3P (0.02 mmol) was added. cWithout Ph3P.
Table 2. Scope of Alkyne and Amide
Table 3. Asymmetric Control
O
Ni(cod)2 (10 mol%)
ligand (20 mol%)
O
N
Ph
Ph
N
Ph
P (10 mol%), AlMe3 (1.0 eq)
Ph
mesitylene, 130
C
1a
2e
3e
entry
ligand
P
yield%(ee%)a entry ligand
P
yield%(ee%)a
Ph3P
Ph3P
1
2
3
4
5
6
7
8
L8
Ph3P
Ph3P
Ph3P
Ph3P
Ph3P
Ph3P
Ph3P
Ph3P
70 (4)
9
L16
L16
L16
L16
L16
L16
L16
L16
91 (79)
L9
72 (11)
43 (22)
95 (8)
10
11
12
13
14
15
16
78 (88)b
40 (90)c
99 (93)c
99 (79)c
65 (57)c
37 (88)c
46 (40)c
Ph3P
L10
L11
L12
L13
L14
L15
(o-Tol)3P
Cy2PTipp
Cy2PPh
CyPPh2
Cy3P
92 (50)
77 (2)
90 (47)
36 (32)
L11, Ar = Ph
O
R
R
Ar
H
N
Ar
L12, Ar = (p-Ph)C6H4
L13, Ar = (p-CF3)C6H4
L14, Ar = (3,5-Ph )C H
6 3
P
O
P
O
O
O
N
O
P
H
2
H
O
O
O
L15, Ar = (3,5-tBu2)C6H3
L16, Ar = 2-Np
L8, R = Ph
L9, R = 1-Np
Ar
L10
Ar
aReaction conditions: 1a (0.1 mmol), 2e (0.3 mmol), mesitylene
(1.0 mL), under N2 for 24 h; isolated yield and ee in parentheses
b
c
determined by chiral HPLC. AlMe3 (0.06 mmol). AlMe3 (0.03
mmol). Tipp = (2,4,6-triisopropyl)phenyl.
aReaction conditions: 1 (0.2 mmol), 2 (0.6 mmol), AlMe3 (0.2
b
Next, we proceeded to investigate the asymmetric version. A
series of ligands derived from commonly-used chiral diamine-
and dihydroxyl-backbones were synthesized and examined in the
cycloaddition reaction of 1a and 2e (Table 3). Results showed that
taddol-derived chiral ligands gave better asymmetric controls
(entries 1–9), especially 2-naphthyl-derived ligand L16 provided
91% yield and 79% ee (enantiomeric excess) (entry 9). Decreas-
mmol), mesitylene (2 mL), under N2 for 24 h. Isolated yield and
1
c
isomer ratios in parentheses were determined by H NMR. The
d
starting amide is a Weinreb amide. Ni(cod)2 (15 mol%) and Al-
e
Me3 (0.4 mmol). Isolated yield for all isomers (81:9:10 isomer
ratio). Np = naphthyl.
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Journal of the American Chemical Society
ing the loadings of AlMe3 gave a better ee, while the yield
termediate, in 85% yield but with partial racemization. Cyclopen-
tene (4e) was treated by oxidation conditions to deliver a deary-
lated amide (4f) in 81% yield.
dropped significantly (entries 10 and 11). However, the use of
different additional phosphine ligand could achieve a good bal-
ance between the yield and the ee (entries 12–16), which was
presumably attributed to an assisted coordination of the phosphine
to the nickel center. For cyclopropane 1a, the best P ligand is (o-
Tol)3P, providing the product 3e in 99% yield and 93% ee (entry
12). The absolute configuration of major enantiomer of the prod-
uct was determined by a single crystal X-ray diffraction (see the
Supporting Information).
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In order to understand the role of ligand and two metals in the
current cycloaddition reaction, some additional experiments were
conducted. Firstly, control experiments showed that the absence
of any of the three components, Ni(cod)2, Ph2P(O)H and AlMe3,
shut down this reaction, implying that each of them is essential to
this reaction. In comparison with cyclopropyl carboxamide, cy-
clopropyl ketone under our conditions mainly led to a significant
amount of byproduct that came from the addition of AlMe3 to the
carbonyl. We also tried to prepare a ligand-Ni-Al complex ac-
cording to Cramer’s method,15 but failed. NMR experiments sug-
gested that the interaction of Ph2P(O)H, AlMe3 and nickel could
generate a bimetallic complex (A) depicted in Scheme 2 (see the
supporting information).17 However, a solid evidence on this in-
termediate is still missing and needs further studies in the future.
Based on these results and Ogoshi’s mechanism,13 we proposed a
catalytic cycle as follows (Scheme 2b): ligand-metal-binding in-
termediate (A) coordinated with the substrate to form intermediate
(B). A subsequent PR3-assisted oxidative addition of nickel with
C–C bond of cyclopropane provided 4-membered nickelacycle
(C), which inserted into alkyne to afford 6-membered nickelacy-
cle (D). A final reductive elimination afforded the desired cyclo-
pentenyl carboxamide and regenerated the catalytic species.
9
After obtaining the optimal conditions, we first explored vari-
ous diarylalkynes 2 in the cycloaddition reaction with cyclopro-
panes 1 (Table 4). In the presence of different additional tertiary
phosphine ligands, diarylalkynes bearing various substituted
groups on the phenyl ring such as Me (3f, 3u, 3v), Et (3w), tBu
(3x), MeO (3g-i), CF3O (3j) and F (3k) were well compatible with
the current reaction, providing 60−99% yield and 86−94% ee. In
addition, di(3-thienyl)alkyne (3n) also led to a good enantioselec-
tive control (86% ee). However, the current method was not suit-
able for dialkylalkynes (3d) and unsymmetrical alkynes (3t), often
leading to low yields and low ees. Notably, when the pyrrolidinyl
of the amide was replaced by other amine groups (4c and 4d), the
ee of product declined significantly, albeit an excellent yield,
suggesting that the stereroselective control was highly sensitive to
steric hindrance of both amides and alkynes.
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Scheme 2. Transformation and Plausible Mechanism
Table 4. Enantioselective Cycloaddition Reaction
R1
R1
R4
a) Deprotection of amide
Ni(cod)2 (10 mol%)
L16 (20 mol%)
P ligand (10 mol%)
O
R1
R1
O
N
MeO
O
N
O
O
R3
R4
O
NH
N
OH
AlMe3 (30 mol%)
N
Ph
4e
CAN
aq. HCl
mesitylene, 130
C
3 or 4a
R3
1
2
CH3CN-H2O
rt
EtOH, reflux
Ph
Ph
Ph
O
O
O
O
Ph
N
N
Ph
Ph
N
N
Ph
OMe
3e, 93% ee
5, 85% yield
4f, 81% yield
OMe
(88% ee)
b) Plausible mechanism
O
(p-MeO)C6H4
(o-MeO)C6H4
Ph
(o-Tol)3P
3e, 99%, 93% ee
p-Tol
Cy2PTipp
3f, 94%, 89% ee
Ph
O
O
Ph
Ph
Ph
P
NR1
R2
(o-Tol)3P
3g, 99%, 90% ee 3h, 59%, 94% ee
Cy2PTipp
P
Al
H
O
PR3
Ni
R1
O
O
O
Ni
(cod)2
AlMe3
O
N
R2
N
N
N
N
Ph
Ph
B
O
OCF3
F
P
Al
Ph
Ph
S
O
OMe
(m-MeO)C6H4
P
AlMe2
O
R3P
Ni
R1
3-thienyl
(p-CF3O)C6H4
(p-F)C6H4
Ni
N
(o-Tol)3P
Cy2PTipp
Cy2PPh
(o-Tol)3P
A
O
R2
Ph
C
3i, 82%, 86% ee
3j, 60%, 90% ee
3k, 66%, 92% ee
3n, 71%, 86% ee
Al
P
Ph
R3P
R'
O
O
O
O
N
O
N
R1
N
N
R
Ni
O
N
R'
R'
R
Et
tBu
R2
NR1R2
R'
D
p-EtC6H4
p-tBuC6H4
In summary, we have developed the first example of nickel-
catalyzed enantioselective cycloaddition reaction of unreactive
cyclopropyl carboxamide with alkyne. A series of synthetically-
useful cyclopentenyl carboxamides are obtained in up to 99%
yield and 94% ee. The cooperation of ligand with Ni and Al may
provide new insights into the C–C bond activation of unreactive
substrates.
o-Tol
m-Tol
Cy2PPh
Cy2PTipp
Cy2PTipp
Cy2PTipp
3u, 65%, 93% ee
3v, 96%, 87% ee
3w,93%, 88% ee
3x, 67%, 93% ee
O
O
N
O
N
O
N
O
N
Ph
Ph
nBu
TMS
Ph
nBu
Ph
Ph
Ph
(o-Tol)3P
>99%, 65% ee
(o-Tol)3P b
(o-Tol)3P b,c
3t, 63%, 77% ee
Cy2PTipp
4d,
>99%, 75% ee
3d, 43%, 59% ee
4c,
ASSOCIATED CONTENT
Supporting Information
aReaction conditions: 1 (0.1 mmol), 2 (0.3 mmol), P ligand (0.01
mmol), mesitylene (1.0 mL), under N2 for 24 h; isolated yield.
bAlMe3 (0.1 mmol). c86:14 dr and ee of major isomer.
The Supporting Information is available free of charge on the
ACS Publications website at DOI. Experimental procedures, char-
acterization data, and spectra of new compounds (PDF)
To demonstrate the applicability of the amide group, further
transformation of products was conducted (Scheme 2a). When
subjected to acidic conditions, cyclopentene (3e) was easily trans-
formed into the corresponding acid (5), a versatile synthetic in-
AUTHOR INFORMATION
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2000, 65, 9230. (b) Wender, P. A.; Pedersen, T. M.; Scanio, M. J. C. J.
Corresponding Author
Am. Chem. Soc. 2002, 124, 15154. (c) Kurahashi, T.; de Meijere, A. Syn-
lett 2005, 2619. (d) Chen, G.-Q.; Zhang, X.-N.; Wei, Y.; Tang, X.-Y.; Shi,
M. Angew. Chem., Int. Ed. 2014, 53, 8492.
1
2
*mcye@nankai.edu.cn.
3
4
5
6
7
8
9
(9) For other types of less-strained cyclopropanes, including cy-
cloylamines in intramolecular cycloaddition, see: (a) Shaw, M. H.; Me-
likhova, E. Y.; Kloer, D. P.; Whittingham, W. G.; Bower, J. F. J. Am.
Chem. Soc. 2013, 135, 4992. (b) Shaw, M. H.; McCreanor, N. G.; Whit-
tingham, W. G.; Bower, J. F. J. Am. Chem. Soc. 2015, 137, 463. (c) Shaw,
M. H.; Croft, R. A.; Whittingham, W. G.; Bower, J. F. J. Am. Chem. Soc.
2015, 137, 8054. (d) McCreanor, N. G.; Stanton, S.; Bower, J. F. J. Am.
Chem. Soc. 2016, 138, 11465. Alkyl cyclopropanes in non-cycloaddition
reactions, see: (e) Hidai, M.; Orisaku, M.; Uchida, Y. Chem. Lett. 1980,
753. (f) Koga, Y.; Narasaka, K. Chem. Lett. 1999, 705. (g) Bart, S. C.;
Chirik, P. J. J. Am. Chem. Soc. 2003, 125, 886. (h) Zhang, Z.-Y.; Liu, Z.-
Y.; Guo, R.-T.; Zhao, Y.-Q.; Li, X.; Wang, X.-C. Angew. Chem., Int. Ed.
2017, 56, 4028.
(10) (a) Liu, L.; Montgomery, J. J. Am. Chem. Soc. 2006, 128, 5348.
For a related highlight, see: (b) Lloyd-Jones, G. C. Angew. Chem., Int. Ed.
2006, 45, 6788.
(11) (a) Ogoshi, S.; Nagata, M.; Kurosawa, H. J. Am. Chem. Soc. 2006,
128, 5350. (b) Tamaki, T.; Nagata, M.; Ohashi, M.; Ogoshi, S. Chem. Eur.
J. 2009, 15, 10083.
Author Contributions
† Q.-S.L. and D.-Y.W. contributed equally to this work.
Notes
The authors declare no competing financial interests.
ACKNOWLEDGMENT
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We thank the National Natural Science Foundation of China
(21402096, 21421062 and 21672107) for financial support.
REFERENCES
(1) For recent reviews on transition-metal-catalyzed C–C cleavage of
cyclopropane, see: (a) Fumagalli, G.; Stanton, S.; Bower, J. F. Chem. Rev.
2017, 117, 9404. (b) Chen, P.-H.; Billett, B. A.; Tsukamoto, T.; Dong, G.
ACS Catal. 2017, 7, 1340. (c) Shaw, M. H.; Bower, J. F. Chem. Commun.
2016, 52, 10817. (d) Souillart, L.; Cramer, N. Chem. Rev. 2015, 115,
9410. (e) Marek, I.; Masarwa, A.; Delaye, P.-O.; Leibeling, M. Angew.
Chem., Int. Ed. 2015, 54, 414. (f) Rubin, M.; Rubina, M.; Gevorgyan, V.
Chem. Rev. 2007, 107, 3117.
(2) For selected reviews and examples on C–C cleavage of donor-
acceptor cyclopropane via Lewis-acid catalysis, see: (a) Schneider, T. F.;
Kaschel, J.; Werz, D. B. Angew. Chem., Int. Ed. 2014, 53, 5504. (b) Car-
son, C. A.; Kerr, M. A. Chem. Soc. Rev. 2009, 38, 3051. (c) Yu, M.;
Pagenkopf, B. L. Tetrahedron 2005, 61, 321. (d) Kang, Q.-K.; Wang, L.;
Liu, Q.-J.; Li, J.-F.; Tang, Y. J. Am. Chem. Soc. 2015, 137, 14594.
(3) For related reviews, see: (a) Zhu, Z.-B.; Wei, Y.; Shi, M. Chem.
Soc. Rev. 2011, 40, 5534. (b) Binger, P.; Büch, H. M. Top. Curr. Chem.
1987, 135, 77.
(4) For related reviews, see: (a) Yu, L.; Liu, M.; Chen, F.; Xu, Q. Org.
Biomol. Chem. 2015, 13, 8379. (b) Brandi, A.; Cicchi, S.; Cordero, F. M.;
Goti, A. Chem. Rev. 2014, 114, 7317. (c) Pellissier, H. Tetrahedron 2014,
70, 4991. (d) Pellissier, H. Tetrahedron 2010, 66, 8341. (e) Masarwa, A.;
Marek, I. Chem. Eur. J. 2010, 16, 9712. (f) Shi, M.; Shao, L.-X.; Lu, J.-
M.; Wei, Y.; Mizuno, K.; Maeda, H. Chem. Rev. 2010, 110, 5883. (g)
Brandi, A.; Cicchi, S.; Cordero, F. M.; Goti, A. Chem. Rev. 2003, 103,
1213. (h) Nakamura, I.; Yamamoto, Y. Adv. Synth. Catal. 2002, 344, 111.
(5) For the seminal report, see: (a) Wender, P. A.; Takahashi, H.;
Witulski, B. J. Am. Chem. Soc. 1995, 117, 4720. For related reviews, see:
(b) Wang, Y.; Yu, Z.-X. Acc. Chem. Res. 2015, 48, 2288. (c) Jiao, L.; Yu,
Z.-X. J. Org. Chem. 2013, 78, 6842. (d) Ylijoki, K. E. O.; Stryker, J. M.
Chem. Rev. 2013, 113, 2244. (e) Pellissier, H. Adv. Synth. Catal. 2011,
353, 189. (f) Butenschön, H. Angew. Chem., Int. Ed. 2008, 47, 5287. (g)
Wender, P. A.; Bi, F. C.; Gamber, G. G.; Gosselin, F.; Hubbard, R. D.;
Scanio, M. J. C.; Sun, R.; Williams, T. J.; Zhang, L. Pure Appl. Chem.
2002, 74, 25.
(6) For cyclopropyl ketones in cycloaddition reaction via Lewis-acid
mediation or catalysis, see: (a) Amador, A. G.; Sherbrook, E. M.; Yoon, T.
P. J. Am. Chem. Soc. 2016, 138, 4722. (b) Tsunoi, S.; Maruoka, Y.; Suzu-
ki, I.; Shibata, I. Org. Lett. 2015, 17, 4010. (c) Huang, H.; Ji, X.; Xiao, F.;
Deng, G.-J. RSC Adv. 2015, 5, 26335. (d) Lu, Z.; Shen, M.; Yoon, T. P. J.
Am. Chem. Soc. 2011, 133, 1162. (e) Bertozzi, F.; Gustafsson, M.; Olsson,
R. Org. Lett. 2002, 4, 3147. (f) Yadav, V. K.; Sriramurthy, V. Angew.
Chem., Int. Ed. 2004, 43, 2669. (g) Han, Z.; Uehira, S.; Tsuritani, T.;
Shinokubo, H.; Oshima, K. Tetrahedron 2001, 57, 987. For a related
review, see: (h) Simone, F. D.; Waser, J. Synthesis 2009, 3353.
(12) (a) Liu, L.; Montgomery, J. Org. Lett. 2007, 9, 3885. (b) Tamaki,
T.; Ohashi, M.; Ogoshi, S. Chem. Lett. 2011, 40, 248.
(13) Tamaki, T.; Ohashi, M.; Ogoshi, S. Angew. Chem., Int. Ed. 2011,
50, 12067.
(14) For Lewis-acid-catalyzed cycloaddition of highly-strained cyclo-
propyl carboxamide, see: (a) Alper, P. B.; Meyers, C.; Lerchner, A.;
Siegel, D. R.; Carreira, E. M. Angew. Chem., Int. Ed. 1999, 38, 3186. (b)
Fischer, C.; Meyers, C.; Carreira, E. M. Helv. Chim. Acta. 2000, 83, 1175.
(c) Lerchner, A.; Carreira, E. M. J. Am. Chem. Soc. 2002, 124, 14826. (d)
Helan, V.; Mills, A.; Drewry, D.; Grant, D. J. Org. Chem. 2010, 75, 6693.
(15) Donets, P. A.; Cramer, N. J. Am. Chem. Soc. 2013, 135, 11772.
(16) (a) L. Ackermann, R. Born, Angew. Chem., Int. Ed. 2005, 44,
2444. (b) Christiansen, A.; Selent, D.; Spannenberg, A.; Baumann, W.;
Franke, R.; Börner, A. Organometallics 2010, 29, 3139. (c) Achard, T.;
Giordano, L.; Tenaglia, A.; Gimbert, Y.; Buono, G. Organometallics
2010, 29, 3936.
(17) For the coordination of AlMe3 to Nickel center, see: Ogoshi, S.;
Ueta, M.; Arai, T.; Kurosawa, H. J. Am. Chem. Soc. 2005, 127, 12810.
(7) For cyclopropyl ketones in non-cycloaddition reactions via transi-
tion-metal catalysis, see: (a) Sumida, Y.; Yorimitsu, H.; Oshima, K. J.
Org. Chem. 2009, 74, 7986. (b) Zhang, Y.; Chen, Z.; Xiao, Y.; Zhang, J.
Chem. Eur. J. 2009, 15, 5208. (c) Sumida, Y.; Yorimitsu, H.; Oshima, K.
J. Org. Chem. 2009, 74, 3196. (d) Ichiyanagi, T.; Kuniyama, S.; Shimizu,
M.; Fujisawa, T. Chem. Lett. 1997, 1149.
(8) For cyclopropyl imines in transition-metal-catalyzed reactions,
wherein imine group was embedded in the ring structure of product, see:
(a) Kamitani, A.; Chatani, N.; Morimoto, T.; Murai, S. J. Org. Chem.
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Ni(0)-AlMe3
2-Np
O
2-Np
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R4
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NR1R2
NR1R2
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up to
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2-Np
Ni-Al bimetallic catalysis
99% yield, 94% ee
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