Copper-catalyzed three-component cascade reaction of alkynes, sulfonyl azides and simple aldehydes/ketones

Article abstract of DOI:10.1039/c6ob00146g

A copper-catalyzed dimethylzinc-promoted three-component cascade reaction of alkynes, sulfonyl azides, and simple aldehydes or ketones is described. Polysubstituted olefins were thus constructed expeditiously in a one-pot procedure under mild conditions.

Full text of DOI:10.1039/c6ob00146g

View Article Online
View Journal
Organic &
Biomolecular
Chemistry
Accepted Manuscript
This article can be cited before page numbers have been issued, to do this please use: Y. Hu, B. Zhou
and C. Wang, Org. Biomol. Chem., 2016, DOI: 10.1039/C6OB00146G.
This is an Accepted Manuscript, which has been through the
Royal Society of Chemistry peer review process and has been
accepted for publication.
Accepted Manuscripts are published online shortly after
acceptance, before technical editing, formatting and proof reading.
Using this free service, authors can make their results available
to the community, in citable form, before we publish the edited
article. We will replace this Accepted Manuscript with the edited
and formatted Advance Article as soon as it is available.
You can find more information about Accepted Manuscripts in the
Information for Authors.
Please note that technical editing may introduce minor changes
to the text and/or graphics, which may alter content. The journal’s
standard Terms & Conditions and the Ethical guidelines still
apply. In no event shall the Royal Society of Chemistry be held
responsible for any errors or omissions in this Accepted Manuscript
or any consequences arising from the use of any information it
contains.
www.rsc.org/obc

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 1 of 5
View Article Online
DOI: 10.1039/C6OB00146G
Journal Name
COMMUNICATION
Copper‐Catalyzed Three‐Component Cascade Reaction of Alkynes,
Sulfonyl Azides and Simple Aldehydes/Ketones
Received 00th January 20xx,
Accepted 00th January 20xx
Yuanyuan Hu, Bingwei Zhou, and Congyang Wang*
DOI: 10.1039/x0xx00000x
www.rsc.org/
A
copper‐catalyzed dimethylzinc‐promoted three‐component develop a three‐component cascade reaction of alkynes,
cascade reaction of alkynes, sulfonyl azides, and simple aldehydes sulfonyl azides, and simple aldehydes/ketones by using
or ketones is described. Polysubstituted olefins were thus copper‐catalysis with the assistance of Me2Zn (Scheme 1b).14
constructed expeditiously in a one‐pot procedure under mild The reaction also features mild reaction conditions, broad
conditions.
substrate scopes, and tolerance of a wide range of functional
groups.
The multicomponent reactions (MCRs) allow multiple bond‐
forming processes in one‐pot operation with simple and
readily available substrates, which shows great advantages in
atomic economy, process practicability, low cost, and
environmental friendliness.1 Thus, development of such
reactions is highly desirable from the synthetic point of view.
In recent years, copper‐catalyzed multicomponent reactions
concerning sulfonyl azides and alkynes2 have attracted a vast
of attention, in which a ketenimine intermediate is generated
in situ3‐12,13 and can be further employed in nucleophilic
addition,3‐7 radical addition,8 and cycloaddition reactions9‐12
.
Scheme 1. Cu‐Catalyzed Three‐Component Reactions of Alkynes, Sulfonyl Azides, and
Carbonyls
Since Chang and coworkers elegantly disclosed the first three‐
component coupling of sulfonyl azides, alkynes, and amines to
synthesize N‐sulfonylamidines by utilizing Cu(I)/Et3N system,3a
a variety of nucleophiles containing N,3 C,4 O,5 and S3o,6 as the
nucleophilic atom have been successfully engaged in this
chemistry. Unsaturated C=N bonds9a‐j,12 and 1,3‐dipoles10 can
also serve as efficient reaction partners via [2+2], [2+2+2] or
[3+2] cycloaddition patterns. In these events, a copper
alkynamide intermediate is often involved. However, this
Cu/amine system shows relatively weaker reactivity for
carbonyls.9k‐m In 2012, Ma et al. reported a highly E‐selective
olefination of ynals through coupling with sulfonyl azides and
alkynes to achieve conjugated enyne scaffolds (Scheme 1a).9l
Recently, we have discovered the important role of
dimethylzinc in cooperating with manganese catalyst for direct
C‐H addition to aldehydes.15 As part of our continuous interest,
we serendipitously found that the reaction of phenylacetylene
1a, p‐toluenesulfonyl azide 2a, and cyclohexanone 3a,
together with 10 mol% CuBr2 and 1.5 equivalents of Me2Zn in
DCE at 60 oC, afforded three‐component coupling product
4aaa in 74% NMR yield (Table 1, entry 1). Screening of solvents
suggested DCE to be the best choice (entries 2‐3).16 To our
delight, the reaction proceeded even better at room
temperature (entries 4‐5). Adjustments of the reaction
concentration and ratio of substrates resulted in increased
yields of 4aaa (entries 6‐8). Variations on bases highlighted the
key role of Me2Zn in this reaction (entries 9‐14). Of note, Et3N,
mostly used in reported Cu‐catalyzed multicomponent
reactions, couldn't promote this transformation at all. Halving
the amount of CuBr2 showed no obvious influence on the
reaction outcome (entry 15). No reaction occurred in the
absence of the copper catalyst and other Cu(I) and Cu(II) salts
were also effective for the reaction (entries 16‐18).16 At last,
Mechanistically,
a lithium ynamidate intermediate was
assumed to form in the presence of a stoichiometric amount
of LiOH, which attributes to the reaction outcome. Herein, we
Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of
Molecular Recognition and Function, Institute of Chemistry, Chinese Academy of
Sciences, Beijing 100190, China. E‐mail: wangcy@iccas.ac.cn.
Electronic Supplementary Information (ESI) available: Experimental details,
characterization data and NMR spectra for all new compounds, and X‐ray data for
4aai (CCDC 1444389) and 4hak (CCDC 1444390). See DOI: 10.1039/x0xx00000x
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1‐3 | 1
Please do not adjust margins

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 2 of 5
COMMUNICATION
Journal Name
4aaa was obtained in 76% isolated yield with 5 mol% Cu(NO3)2
as the catalyst (entry 19).
O
View Article Online
5 mol% Cu(NO3)2
DOI: 10.1039/C6OB00146G
O
R
1.5 equiv Me2Zn
NHTs
TsN3
+
+
R
DCE (1 M), r.t., 6 h
then acidic work-up
Table 1. Optimization of Reaction Conditionsa
3a
1
2a
4
O
O
4aaa: R= H, 76%
R
S
4baa: R= p-Me, 65%
4caa: R= p-OMe, 55%
4daa: R= p-F, 51%a
4eaa: R= m-Me, 74%
NHTs
NHTs
4faa: 71%a
T
yield
(%)b
74
entry
cat.
base
Me2Zn
solvent
DCE
(oC)
O
1
CuBr2
CuBr2
CuBr2
CuBr2
CuBr2
CuBr2
CuBr2
CuBr2
CuBr2
CuBr2
CuBr2
CuBr2
CuBr2
CuBr2
CuBr2
60
O
O
N
Boc
NHTs
2
Me2Zn
Me2Zn
Me2Zn
Me2Zn
Me2Zn
Me2Zn
Me2Zn
Et2O
toluene
DCE
60
68
24
78
66
85
77
85
0
NHTs
NHTs
3
60
4iaa: 45%a
4
r.t.
80
4gaa: 51%a
4haa: 59%a
R
PhCOO
5
DCE
O
O
O
O
3
DCEc
DCEd
DCEc
DCEc
DCEc
DCEc
DCEc
DCEc
DCEc
DCEc
DCEc
DCEc
DCEc
DCEc
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
TMS
6
NHTs
NHTs
NHTs
NHTs
7
8e
4jaa: R = H, 72%a
4kaa: R = Cl, 53%
4laa: 57% 4maa: 69%a
4naa: 55%a
9e
‐
f
Scheme 2. Substrate Scope for Alkynes. Reaction conditions: 1 (0.5 mmol), 2a (1.0
mmol), 3a (1.0 mmol), Cu(NO3)2 (0.025 mmol), Me2Zn (0.75 mmol), DCE (0.5 mL), r.t., 6
h. Isolated yields are shown. a Cu(NO3)2 (0.05 mmol).
10e
11e
12e
13e
14e
15e,g
16e
17e,g
18e,g
19e,g
Et2Zn
25
0
MeMgBr
n‐BuLi
LiOH
0
0
Et3N
0
Me2Zn
Me2Zn
Me2Zn
Me2Zn
Me2Zn
82
0
h
‐
CuBr
70
80
88 (76)i
Cu(OAc)2
Cu(NO3)2
a Reaction conditions unless otherwise noted: 1a (0.2 mmol), 2a (0.8 mmol), 3a
(0.4 mmol), catalyst (0.02 mmol), base (0.3 mmol), solvent (0.5 mL), 60 oC, 6 h,
under N2 atmosphere. b Yields determined by 1H NMR analysis. c 0.2 mL. d 1.0 mL.
e 1a/2a/3a = 1:2:2. f No base. g catalyst (0.01 mmol). h No catalyst. i Isolated yield
on 0.5 mmol scale.
Scheme 3. Substrate Scope for Azides. Reaction conditions: 1a (0.5 mmol), 2 (1.0 mmol),
3a (1.0 mmol), Cu(NO3)2 (0.025 mmol), Me2Zn (0.75 mmol), DCE (0.5 mL), r.t., 6 h.
Isolated yields are shown. a Cu(NO3)2 (0.05 mmol).
With the optimized conditions in hand, we first investigated
the scope of alkynes (Scheme 2). Both electron‐donating and ‐
withdrawing groups on aromatic alkynes were tolerated
affording the expected products in good yields (4aaa−eaa). 3‐
Ethynylthiophene and 3‐ethynylindole as well as 2‐
The generality of carbonyls
3 was further examined through
the reactions with alkyne 1a and azide 2a (Scheme 4). Both
cyclic ketones of varied ring sizes and acyclic ketones were
competent to participate in the tandem reaction giving the
ethynylnaphthalene were all amenable to this protocol under
corresponding
products
successfully
(
4aab
‐
g).
The
slightly modified reaction conditions (4faa
enyne and aliphatic alkynes were also suitable reaction
partners (4iaa maa). Functional groups like halogen atoms
4daa 4kaa), ester (4laa), and silyl group (4naa) were all
−haa). Furthermore,
employment of unsymmetrical ketone 2‐pentanone 3h and
acetophenone 3i resulted in a mixture of two stereoisomers
with 4aah and 4aai as the major product respectively. The
structure of 4aai was unambiguously confirmed by single
crystal X‐ray diffraction analysis. Besides, both aromatic and
aliphatic aldehydes were suitable substrates for this protocol
−
(
,
compatible with the reaction conditions.
We next tested the scope of azides with phenylacetylene 1a
and cyclohexanone 3a as model coupling partners (Scheme 3).
Aryl sulfonyl azides bearing electronically varied substituents
were all successfully involved in this cascade reaction
(
4aaj‐k, 4hak). Notably, these reactions showed an excellent
stereoselectivity favoring the formation of E‐configured
products. The structure of 4hak was again confirmed by single
crystal X‐ray diffraction analysis. Functionalities such as olefin
(
4aba−ada). 2‐Naphthalene sulfonyl azide 2e showed
comparable reactivity affording the three‐component coupling
product smoothly (4aea). Methanesulfonyl azide 2f was also
an effective substrate to deliver the corresponding product
and bromo groups were well compatible (4aal‐m). When
complex aldehyde 3n derived from ursodeoxycholic acid was
subjected to the reaction conditions, the three‐component
coupling product 4aan was obtained in excellent chemo‐ and
stereoselectivity with the ketone moieties remaining intact.
(
4afa), albeit with relatively lower reactivity.
2 | J. Name., 2012, 00, 1‐3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 3 of 5
Journal Name
COMMUNICATION
View Article Online
N
Cu(NO3)2 (1 equiv)
Me2Zn (1.5 equiv)
a)
N
b)
3a (2 equiv)
1a
Ph
DOI: 10.1039/C6OB00146G
N
Ts
5 mol% Cu(NO3)2
+
Ph
DCE, r.t., 6 h
then H+
Me2Zn (1.5 equiv)
H
TsN3 2a
5aa
4aaa
5aa: 15%a
N.D.
DCE, r.t., 6 h
N.D.
no Cu(NO3)2
no Me2Zn
N.D.
N
N
N
N
n-BuLi (1.1 equiv)
3a (2 equiv)
r.t., 6 h
N
Ts
N Ts
c)
4aaa
58%a
THF, 0 oC, 0.5 h
Ph
Ph
H
5aa
Li
Li-I
3a
Cu(NO3)2
(1.5 equiv)
0 oC, 0.5 h
CuBr
(2 equiv)
4aaa
r.t., 6 h
3a
N.D.
(1.5 equiv)
(2 equiv)
4aaa
n-BuLi
(1.1 equiv)
N
0 oC, 0.5 h
r.t., 6 h
N
38%a
N
Ts
d) 5aa
3a
(2 equiv)
ZnI2
(1.5 equiv)
Ph
THF
0 oC, 0.5 h
Li
Li-I
4aaa
10%a
0 oC, 0.5 h
r.t., 6 h
Me2Zn
3a
(1.5 equiv)
0 oC, 0.5 h
(2 equiv)
4aaa
30%a
r.t., 6 h
Scheme 5. Mechanism Studies. a Yields determined by 1H NMR analysis. N.D. = Not
Detected.
Scheme 4. Substrate Scope for Carbonyls. Reaction conditions: 1a (0.5 mmol), 2a (1.0
mmol), 3 (1.0 mmol), Cu(NO3)2 (0.025 mmol), Me2Zn (0.75 mmol), DCE (0.5 mL), r.t., 6 h.
Isolated yields are shown. a Combined yield of two isomers. b Determined by 1H NMR
analysis and the major product is shown. c Isolated yield of the major isomer. d only E‐
configured product was detected by 1H NMR analysis of the crude reaction mixture. e
Determined by GC‐MS. f Cu(NO3)2 (0.05 mmol). g DCE (0.4 M).
To elucidate the possible reaction mechanism, a series of
experiments was conducted. First, the two‐component
reaction of alkyne 1a and azide 2a gave 1‐sulfonyltriazole 5aa
in 15% NMR yield after hydrolysis (Scheme 5a). No formation
of 5aa was observed in the absence of either Cu(NO3)2 or
Me2Zn, which indicated the crucial roles of Cu(NO3)2 and
Me2Zn in this reaction. Then, the reaction of 1‐sulfonyltriazole
5aa and cyclohexanone 3a was carried out under the standard
conditions (Scheme 5b). No expected product 4aaa was
detected, which ruled out the intermediacy of 5aa in the
three‐component coupling reaction. We assumed that 5‐
metalated‐1‐sulfonyltriazole might be the key intermediate of
the three‐component reaction.17 Therefore, lithiation of 1‐
sulfonyltriazole 5aa9f followed by addition of cyclohexanone 3a
was conducted, which afforded the expected product 4aaa in
58% NMR yield (Scheme 5c). However, the direct use of n‐BuLi
for the three‐component coupling reaction was unsuccessful
presumably due to its incompatibility with the reaction
substrates and/or catalyst (Table 1, entry 12). To ascertain the
key metal species, lithiated triazole Li‐I was first treated with
Cu(NO3)2, CuBr, ZnI2, and Me2Zn respectively18‐19 and then
reacted with cyclohexanone 3a (Scheme 5d). No product 4aaa
was detected in the reaction of copper(II) species and 3a while
those of copper(I) and zinc species delivered 4aaa in 38%, 10%,
and 30% yield, respectively. These results implied that the
roles of Me2Zn might be complicated in the reaction such as
being the base, transmetalation reagent, reductant (CuII to CuI)
or Lewis acid (activating carbonyls) and awaited further
investigations.20
Scheme 6. A Plausible Mechanism.
Based on the above experiments and literature clues,9,17,21
a
plausible mechanism is shown in Scheme 6. Initial Cu‐catalyzed
cycloaddition of alkynes and sulfonyl azides in the presence of
Me2Zn affords copper intermediate Cu‐I, which then releases
dinitrogen to generate metal ynamidate M‐II or its isomer
ketenimine M‐III (M = Cu, Zn). Subsequent nucleophilic
addition to aldehydes/ketones gives metal alkoxide M‐IV. An
intramolecular cyclization of M‐IV leads to four‐membered
species M‐V, which further undergoes a ring‐opening step
furnishing product
.
4 after hydrolysis of amide zincate Zn‐
VI 20,21
In conclusion, we have developed a three‐component one‐
pot procedure for efficient synthesis of polysubstituted olefins
from common and easily available alkynes, sulfonyl azides, and
simple aldehydes/ketones by the combinative use of the
copper catalyst and Me2Zn. This protocol showcases broad
substrate scopes, mild reaction conditions, and good
compatibility of functional groups.
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1‐3 | 3
Please do not adjust margins

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 4 of 5
COMMUNICATION
Journal Name
4
5
(a) S. H. Cho and S. Chang, Angew. Chem. Int. Ed., 2008, 47,
Financial support from the National Basic Research Program
of China (973 Program) (No. 2012CB821600) and the National
Natural Science Foundation of China (21322203, 21272238,
21472194) are gratefully acknowledged.
2836. (b) J. Wang, J. Wang, Y. Zhu, P. DLuOIa: 1n0d.1Y03. V9Wi/eCwa6nAOrgtBi,c0lCe0hO1e4nl6minGe.
Commun., 2011, 47, 3275. (c) Y. Shang, K. Ju, X. He, J. Hu, S.
Yu, M. Zhang, K. Liao, L. Wang and P. Zhang, J. Org. Chem.,
2010, 75, 5743. (d) I. Yavari, A. Sheikhi, M. Nematpour and Z.
Taheri, Helv. Chim. Acta, 2015, 98, 534.
(a) S. H. Cho, E. J. Yoo, I. Bae and S. Chang, J. Am. Chem. Soc.,
2005, 127, 16046. (b) M. P. Cassidy, J. Raushel and V. V.
Fokin, Angew. Chem. Int. Ed., 2006, 45, 3154. (c) E. J. Yoo, I.
Notes and references
1
For selected reviews, see: (a) A. Dömling and I. Ugi, Angew.
Chem. Int. Ed., 2000, 39, 3168. (b) H. Bienaymé, C. Hulme, G.
Oddon and P. Schmitt, Chem. Eur. J., 2000, 6, 3321. (c) B. B.
Bae, S. H. Cho and S. Chang, Org. Lett., 2006,
8, 1348. (d) S.
Cui, X. Lin and Y. Wang, Org. Lett., 2006, , 4517. (e) S. H.
8
Cho and S. Chang, Angew. Chem. Int. Ed., 2007, 46, 1897. (f)
E. J. Yoo, S. H. Park, S. H. Lee and S. Chang, Org. Lett., 2009,
11, 1155. (g) R. Husmann, Y. S. Na, C. Bolm and S. Chang,
Chem. Commun., 2010, 46, 5494. (h) W. Song, W. Lu, J. Wang,
P. Lu and Y. Wang, J. Org. Chem., 2010, 75, 3481. (i) W. Song,
M. Lei, Y. Shen, S. Cai, W. Lu, P. Lu and Y. Wang, Adv. Synth.
Catal., 2010, 352, 2432. (j) Y. Liu, X. Wang, J. Xu, Q. Zhang, Y.
Zhao and Y. Hu, Tetrahedron, 2011, 67, 6294. (k) S. Li and J.
Wu, Chem. Commun., 2012, 48, 8973. (l) G. Murugavel and T.
Punniyamurthy, Org. Lett., 2013, 15, 3828. (m) I. Yavari, M.
Ghazanfarpur‐Darjani, M. J. Bayat and A. Malekafzali, Synlett,
2014, 25, 959.
(a) I. Yavari, T. Damghani and M. Nematpour, Helv. Chim.
Acta, 2013, 96, 2214. (b) I. Yavari, M. Nematpour and Z.
Tavakoli, Helv. Chim. Acta, 2013, 96, 2141. (c) B. Jiang, X. Tu,
X. Wang, S. Tu and G. Li, Org. Lett., 2014, 16, 3656.
I. Yavari, Z. Taheri, M. Nematpour and A. Sheikhi, Helv. Chim.
Acta, 2015, 98, 343.
Toure and D. G. Hall, Chem. Rev., 2009, 109, 4439. (d) J. D.
Sunderhaus and S. F. Martin, Chem. Eur. J., 2009, 15, 1300. (e)
B. Ganem, Acc. Chem. Res., 2009, 42, 463. (f) E. Ruijter, R.
Scheffelaar and R. V. A. Orru, Angew. Chem. Int. Ed., 2011,
50, 6234. (g) C. Graaff, E. Ruijter and R. V. A. Orru, Chem. Soc.
Rev., 2012, 41, 3969.
2
For selected examples of Rh‐catalyzed reactions of triazoles
derived from alkynes and sufonyl azides, see: (a) T. Horneff,
S. Chuprakov, N. Chernyak, V. Gevorgyan and V. V. Fokin, J.
Am. Chem. Soc., 2008, 130, 14972. (b) T. Miura, M. Yamauchi
and M. Murakami, Chem. Commun., 2009, 1470. (c) N.
Grimster, L. Zhang and V. V. Fokin, J. Am. Chem. Soc., 2010,
132, 2510. (d) B. Chattopadhyay and V. Gevorgyan, Org. Lett.,
2011, 13, 3746. (e) T. Miura, T. Biyajima, T. Fujii and M.
Murakami, J. Am. Chem. Soc., 2012, 134, 194. (f) T. Miura, T.
Tanaka, K. Hiraga, S. G. Stewart and M. Murakami, J. Am.
Chem. Soc., 2013, 135, 13652. (g) T. Miura, T. Tanaka, T.
Biyajima, A. Yada and M. Murakami, Angew. Chem. Int. Ed.,
2013, 52, 3883. (h) S. Chuprakov, S. W. Kwok and V. V. Fokin,
J. Am. Chem. Soc., 2013, 135, 4652. (i) E. E. Schultz and R.
Sarpong, J. Am. Chem. Soc., 2013, 135, 4696. (j) B. T. Parr, S.
6
7
8
9
X. He, Y. Shang, J. Hu, K. Ju, W. Jiang and S. Wang, Sci China
Chem, 2012, 55, 214.
For [2+2] cycloaddition reactions, see: (a) M. Whiting and V.
V. Fokin, Angew. Chem. Int. Ed., 2006, 45, 3157. (b) X. Xu, D.
Chen, J. Li, H. Guo and J. Yan, Org. Lett., 2007, 9, 1585. (c) Y.
A. Green and H. M. L. Davies, J. Am. Chem. Soc., 2013, 135
,
4716. (k) J. E. Spangler and H. M. L. Davies, J. Am. Chem. Soc.,
2013, 135, 6802. (l) M. Zibinsky and V. V. Fokin, Angew.
Chem., Int. Ed., 2013, 52, 1507. (m) R. Liu, G. Winston‐
McPherson and W. Tang, Chem. Commun., 2013, 49, 4376. (n)
Shang, X. He, J. Hu, J. Wu, M. Zhang, S. Yu and Q. Zhang, Adv.
Synth. Catal., 2009, 351, 2709. (d) K. Namitharan and K.
Pitchumani, Org. Biomol. Chem., 2012, 10, 2937. (e) X. Yi, B,‐
D. Barry, P. Liao and X. Bi, Synthesis, 2012, 44, 1323. (f) Y.
Shang, K. Liao, X. He and J. Hu, Tetrahedron, 2013, 69, 10134.
(g) S. Gouthaman, P. Shanmugam and A. B. Mandal,
Tetrahedron, 2013, 54, 3007. (h) Y. Xing, H. Zhao, Q. Shang, J.
Wang, P. Lu and Y. Wang, Org. Lett., 2013, 15, 2668. (i) S.
Periyaraja, P. Shanmugam and A. B. Mandal, Eur. J. Org.
Chem., 2014, 954. (j) J. Wang, J. Liu, H. Ding, J. Wang, P. Lu
and Y. Wang, J. Org. Chem., 2015, 80, 5842. (k) W. Yao, L.
Pan, Y. Zhang, G. Wang, X. Wang and C. Ma, Angew. Chem.
Int. Ed., 2010, 49, 9210. (l), D. Chen, F. Ling, Z. Li, W. Yao and
C. Ma, Org. Lett., 2012, 14, 3146. (m) Z. Li, F. Lin, D. Chen and
C. Ma, Org. Lett., 2014, 16, 1822.
S. Park, W.‐S. Yong, S. Kim and P. H. Lee, Org. Lett., 2014, 16
,
4468. (o) C.‐E. Kim, S. Park, D. Eom, B. Seo and P. H. Lee, Org.
Lett., 2014, 16, 1900. (p) X. Lei, L. Li, Y.‐P. He and Y. Tang, Org.
Lett., 2015, 17, 5224.
3
(a) I. Bae, H. Han and S. Chang, J. Am. Chem. Soc., 2005, 127
,
,
2038. (b) S. Cui, J. Wang and Y. Wang, Org. Lett., 2007,
9
5023. (c) J. Kim, S. Y. Lee, J. Lee, Y. Do and S. Chang, J. Org.
Chem., 2008, 73, 9454. (d) S. Cui, J. Wang and Y. Wang, Org.
Lett., 2008, 10, 1267. (e) S. Cui, J. Wang and Y. Wang,
Tetrahedron, 2008, 64, 487. (f) W. Lu, W. Song, D. Hong, P.
Lu and Y. Wang, Adv. Synth. Catal., 2009, 351, 1768. (g) J.
She, Z. Jiang and Y. Wang, Synlett, 2009, 12, 2023. (h) H. Jin,
X. Xu, J. Gao, J. Zhong and Y. Wang, Adv. Synth. Catal., 2010,
10 For [3+2] cycloaddition reactions see: (a) S. Li, Y. Luo and J.
Wu, Org. Lett., 2011, 13, 4312. (b) K. Namitharan and K.
Pitchumani, Org. Lett., 2011, 13, 5728. (c) I. Yavari, M.
Nematpour, S. Yavari and F. Sadeghizadeh, Tetrahedron
Letters, 2012, 53, 1889. (d) I. Yavari and M. Nematpour, Helv.
Chim. Acta, 2013, 96, 2098.
11 For [4+2] cycloaddition reactions see: (a) K. Namitharan and
K. Pitchumani, Adv. Synth. Catal., 2013, 355, 93. (b) I. Yavari,
M. Nematpour and M. A. Amiri, Tetrahedron Letters, 2014,
55, 4994. (c) X. Yan, F. Ling, Y. Zhang and C. Ma, Org. Lett.,
2015, 17, 3536.
12 For [2+2+2] cycloaddition reactions see: D. Ramanathan and
K. Pitchumani, J. Org. Chem., 2015, 80, 10299.
13 For a proposed carbene intermediate, see: J. S. Alford and H.
M. L. Davies, J. Am. Chem. Soc., 2014, 136, 10266.
14 During the submission of this work, we are aware that Ma et
al. just reported a Cu‐catalyzed reaction of terminal alkynes,
sulfonyl azides, and aldehydes by using t‐BuOLi to form N‐
tosylacrylamides: J. Wu, D. Wang, Y. Wan and C. Ma, Chem.
352, 347. (i) Z. Chen, D. Zheng and J. Wu, Org. Lett., 2011, 13
,
848. (j) Z. Chen, C. Ye, L. Gao and J. Wu, Chem. Commun.,
2011, 47, 5623. (k) Z. Jiang, P. Lu and Y. Wang, Org. Lett.,
2012, 14, 6266. (l) W. Chen, L. Jin, Y. Zhu and W. Mo,
ARKIVOC, 2012, 295. (m) I. Yavari, M. Nematpour and M.
Ghazanfarpur‐Darjani, Tetrahedron Lett., 2012, 53, 942. (n) I.
Yavari and M. Nematpour, Synlett, 2012, 23, 2215. (o) T.
Yang, H. Cui, C. Zhang, L. Zhang and C.‐Y. Su, Inorg. Chem.,
2013, 52, 9053. (p) J. R. Suárez, J. Kwiczak, K. Grenda, M. J.
Jimeno, J. L. Chiara, Adv. Synth. Catal., 2013, 355, 913. (q) F.
Zhou, X. Liu, N. Zhang, Y. Liang, R. Zhang, X. Xin and D. Dong,
Org. Lett., 2013, 15, 5786. (r) D. Ramanathan and K.
Pitchumani, Eur. J. Org. Chem., 2015, 463. (s) V. Mahendran
and S. Shanmugam, RSC Adv., 2015,
5, 20003. (t) W. Choi, J.
Kim, T. Ryu, K.‐B. Kim and P. H. Lee, Org. Lett., 2015, 17
,
3330. (u) G. Murugavel and T. Punniyamurthy, J. Org. Chem.,
2015, 80, 6291.
4 | J. Name., 2012, 00, 1‐3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 5 of 5
Journal Name
COMMUNICATION
Commun. 2016, 52, 1661. However, the use of simple
View Article Online
DOI: 10.1039/C6OB00146G
ketones is not involved in this report.
15 B. Zhou, Y. Hu and C. Wang, Angew. Chem., Int. Ed., 2015, 54
13659.
,
16 For more details, see Electronic Supplementary Information.
17 E. J. Yoo, M. Ahlquist, I. Bae, K. B. Sharpless, V. V. Fokin and S.
Chang, J. Org. Chem., 2008, 73, 5520.
18 For Li‐Zn exchange, see: (a) Y. Wang, B. Quillian, C. S.
Wannere, P. Wei, P. R. Schleyer and G. H. Robinson,
Organometallics, 2007, 26, 3054. (b) C. J. Cordier, R. J.
Lundgren and G. C. Fu, J. Am. Chem. Soc., 2013, 135, 10946.
(c) D. T. Hurd, J. Org. Chem., 1948, 13, 711. (d) M. Uchiyama,
M. Kameda, O. Mishima, N. Yokoyama, M. Koike, Y. Kondo
and T. Sakamoto, J. Am. Chem. Soc., 1996, 118, 8733.
19 For Li‐Cu exchange, see: S. H. Bertz, J. Am. Chem. Soc., 1991,
113, 5470.
20 The insightful comments on the possible reaction
mechanism from the reviewers are highly appreciated.
21 For a general review on ynamides, see: (a) K. A. DeKorver, H.
Li, A. G. Lohse, R. Hayashi, Z. Lu, Y. Zhang and R. P. Hsung,
Chem. Rev., 2010, 110, 5064; For selected examples of [2+2]
cyclizations of ynamides with carbonyls, see: (b) R. P. Hsung,
C. A. Zificsak, L.‐L. Wei, C. J. Douglas, H. Xiong and J. A.
Mulder, Org. Lett., 1999,
1
, 1237; (c) K. C. M. Kurtz, R. P.
Hsung and Y. Zhang, Org. Lett., 2006,
8
, 231; (d) L. You, Z. F.
Al‐Rashid, R. Figueroa, S. K. Ghosh, G. Li, T. Lu and R. P.
Hsung, Synlett, 2007, 1656.
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1‐3 | 5
Please do not adjust margins