Direct Tryptophols Synthesis from 2-Vinylanilines and Alkynes via C - C Triple Bond Cleavage and Dioxygen Activation

Article abstract of DOI:10.1021/jacs.6b08094

An unexpected metal-free C - C triple bond cleavage, dioxygen activation, and reassembly into tryptophol derivatives has been developed. This chemistry provides a novel, simple, and efficient approach to highly valuable tryptophol derivatives from simple substrates under mild conditions. The mechanistic studies may promote the discovery of new methodologies through C-C bond cleavage and dioxygen activation.

Full text of DOI:10.1021/jacs.6b08094

Subscriber access provided by EPFL | Scientific Information and Libraries
Communication
Direct Tryptophols Synthesis from 2-Vinylanilines and Alkynes
via C#C Triple Bond Cleavage and Dioxygen Activa-tion
Tao Shen, Yiqun Zhang, Yu-Feng Liang, and Ning Jiao
J. Am. Chem. Soc., Just Accepted Manuscript • Publication Date (Web): 20 Sep 2016
Downloaded from http://pubs.acs.org on September 20, 2016
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a free service to the research community to expedite the
dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts
appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been
fully peer reviewed, but should not be considered the official version of record. They are accessible to all
readers and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered
to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published
in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just
Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor
changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers
and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors
or consequences arising from the use of information contained in these “Just Accepted” manuscripts.
Journal of the American Chemical Society is published by the American Chemical
Society. 1155 Sixteenth Street N.W., Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the course
of their duties.

Page 1 of 5
Journal of the American Chemical Society
1
2
3
4
5
6
7
8
Direct Tryptophols Synthesis from 2-Vinylanilines and Al-
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
kynes via C≡C Triple Bond Cleavage and Dioxygen Activation
Tao Shen,† Yiqun Zhang,† Yu-Feng Liang,† and Ning Jiao*,†,‡
† State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University Xue Yuan
Road 38, Beijing 100191 (China);
‡ State Key Laboratory of Organometallic Chemistry, Chinese Academy of Sciences. Shanghai 200032 (China)
Supporting Information Placeholder
strategy for the synthesis of complex and highly valuable tryp-
ABSTRACT: An unexpected metal-free C≡C triple bond cleav-
tophol derivatives under very mild conditions; 4) A reasonable
age, dioxygen activation, and reassembly into tryptophol deriva-
mechanism is proposed, which may promote the discovery of new
tives has been developed. This chemistry provides a novel, simple,
methodologies for C-C bond cleavage and dioxygen activation.
and efficient approach to highly valuable tryptophol derivatives
from simple substrates under mild conditions. The mechanistic
Scheme 1. Bond Cleavage for Tryptophols.
studies may promote the discovery of new methodologies through
C-C bond cleavage and dioxygen activation.
When 2-vinylaniline 1a and dimethyl acetylenedicarboxylate
With respect to simple and efficient methodologies, the
synthesis of complex compounds by employing simple and readi-
ly available substrates as starting materials has always been de-
2a were initially investigated in our Pd-catalyzed dehydrogenative
annulation for the corresponding indole synthesis,11 to our delight,
sired.1 Bond cleavage and reassembly strategy provides great
opportunities to reach very incredible and more complex products.
However, although the reactions through C-C bond cleavage have
attracted considerable attentions,2 the transformations with
unstrained C-C bond cleavage still remains a challenging issue.3-4
Moreover, the cleavage and reassembly of C≡C triple bond
located in one product for the synthesis more complex compounds
is rarely achieved.5-6
an unexpected tryptophol product 3a was obtained in 58% yield
in DMSO under dioxygen atmosphere (Table 1, entry 1). On the
contrary, only trace amount of 3a was observed with copper
catalyst (entry 2). Further investigation (see SI) demonstrated that
3a could be obtained without any metal catalyst in 60% yield
(Table 1, entry 3). It seems that concentration of the reaction
system plays an important role for high efficiency (cf. entries 3
and 4). Molecular oxygen is essential for this transformation.
When the reaction was performed under air, the yield decreaced
obviously (entry 7). No product was obtained uner Ar atmosphere
(entry 8). The reactions in other solvents such as THF, toluene,
1,4-dioxane, DCE did not work (see SI).
Molecular oxygen is a green oxidant as well as an ideal oxygen
source for the construction of oxygen-containing compounds
because of its inexpensive, aboundent, and environmentally
benign characters.7 In the past decades, although many transition
metals have been significantly applied in the oxygenation
reactions with molecular oxygen,8 only few examples have been
demonstrated on transition metal-free dioxygen activation
mediated by organic molecules.9
Table 1. Optimization for the Tryptophols Synthesis.a
According to the atom economy concept, herein we report an
unexpected metal-free C≡C triple bond cleavage, dioxygen
activation, and reassembly into tryptophol derivatives (Scheme 1),
which are common structural motifs in natural products and
pharmaceutical drugs, as well as important intermediates and
building blocks in organic synthesis.10 The present novel tryp-
tophol construction protocol has several significant advantages: 1)
The incredible chemical bond cleavage of alkynes and molecular
oxygen occured and reassembled in one product molecule. To the
best of our knowledge, this is the first direct synthesis of
typtophol derivatives by oxygenation strategy via O2 activation as
well as C-C bond cleavage from simple and readily available
substrates; 2) This protocol is very simple under metal-free
conditions, without the addition of any acid, base or other
additives, which avoids the strict transition-metal removal process
from the products; 3) This chemistry provides a novel and simple
a
Reaction conditions: 1a (0.2 mmol), 2a (0.4 mmol), catalyst
o
(0.01 mmol), DMSO (2 mL), stirred at 80 C under O2 for 12 h.
Isolated yields. b DMSO (1.0 mL). under air. under Ar. DMSO
c
d
= dimethyl sulfoxide.
Table 2. The Substrate Scope of this Transformation.a
-1-
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 2 of 5
1
2
3
4
5
6
7
8
9
yield. The elimination reaction of 3a provided 7b in 40% yield,
which could be used for further synthesis of biologically active
molecules. Moreover, Cu-catalyzed click reaction was employed
to give triazole 7c in 76% yield via intermediate 7a. Due to the
unique structure of 3a, direct intramolecular condensation was
allowed to afford lactones 7d in 90% yield. Lactam 7e could be
obtained in 55% yield under KOH/MeOH conditions, and the
further esterification of 7e resulted in β-carboline skeletons 7f,
which has potential activity to bind brain GABA receptors.13
Lactone 7g could be highly efficiently prepared in 88% yield by
direct intramolecular condensation of 3a. In addition, as an
important class of tryptophan derivatives, primary amine 7h could
be obtained via the reduction of 7a in 65% yield. Thus, the
presented methodology could be a complimentary tool to access a
useful library of tryptophols, lactones, lactams, and β-carboline
alkaloids derivatives.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Table 3. The Substrate Scope of Alkynes.a
a Conditions see entry 6, Table 1. b Conditions: (1) 1a (0.1 mmol),
2a (0.09 mmol), Cu(OTf)2 (10 mol%), 4Å MS, THF (0.1 mL),
a
b
Standard conditions: see entry 4, Table 1. Isolated yields. At
o
120 oC for 24 h.
stirred at 45 C under Ar for 12 h; (2) DMSO (1 mL), stirred at
100 oC under O2 for 12 h. Isolated yields.
Various 2-vinylaniline containing different functional groups
worked well leading to the desired tryptophols in moderate to
good yields (Table 2). Notably, 1g, which was prepared from
analgesic benzocaine, could smoothly generate 3g in moderate
yield. Unfortunately, the reactions of secondary amines and
aliphatic homoallylamines stopped at hydroamination step
without the tryptophols products formation (3y, also see SI). The
gram scale reaction afforded 3a in 82% yield (Eq. 1). Moreover,
the structure of 3a was confirmed by the by X-ray structure of its
derivative 4 (Eq. 1).
Table 4. Peroxide Tryptophol Synthesis.a
a Reaction conditions: 1a (0.2 mmol), 2a (0.4 mmol), 1,4-dioxane
(1 mL), stirred at 80 oC under O2 for 12 h. Isolated yields.
For the scope of alkynes, to our delight, the fluoroalkyl alkynes
worked well and regioselectively produced the corresponding
tryptophol products 3aa and 3ab (Table 3). Furthermore, by using
a simple tandem process, phenyl substituted alkynes could also be
employed in this protocol (3ac-3ae). It is noteworthy that these
reaction showed high regioselectivity with only one isomer
detected.
Scheme 2. Further Transformations of Product 3a.
Interestingly, when changed the solvent from DMSO to 1,4-
dioxane, the corresponding peroxide tryptophol 5a was obtained
in 72% yield instead of 3a (Table 4). Thus, the tryptophols
products could be easily switched by the selection of solvent. A
range of different substituents at aromatic ring were compatible to
furnish highly functionalized peroxide tryptophols derivatives in
moderate to good yields (5b-f). The structure of 5a was confirmed
by COSEY spectroscopy and its derivative 6 generated from
hydroperoxide12 was further proved by X-ray (Eq. 2).
The tryptophol products 3 could be further transferred to other
important compounds (Scheme 2). For examples, the
nucleophilic substitution of 3a with NaN3 generated 7a in 78%
Conditions: a-h, for the details please see SI.
- 2 -
ACS Paragon Plus Environment

Page 3 of 5
Journal of the American Chemical Society
1
2
3
4
5
6
7
8
9
10
procuct 3a. In addition, the reactive intermediate B could be
trapped by 1,1-diphenylethylene in the absence of O2 to form
intermediate D, which produces the product 11 through a similar
1,5-HAT process.
In addition, the present protocol also provides efficient
synthetic routes to biologically active molecules synthesis. The
direct silver and copper-mediated oxidative decarboxylation of 7e
occurred to generate β-carboline alkaloids 8 in 50% yield (Eq. 3),
which is separated from the stems of picrasma quassioides.14
Moreover, the selective NMDA antagonist15 9 could be efficiently
synthesized from 3a via 7b (Eq. 4).
To gain some insight into the mechanism, some control exper-
iments were investigated. When the reaction was carried out in the
presence of 2.0 eq of H218O, no 18O labeled product was detected
(Eq. 5). On the contrary, 18O product and the 16O product were
detected with the ratio of 4:1 when 18O2 was filled in the reaction
system (Eq. 6). These results demonstrate that oxygen atom of
hydroxyl in the product is mainly originated from molecule oxy-
gen. The reaction of [D2]-1a was tested under standard conditions,
and [D2]-3a was obtained in 82% yield (Eq. 7), which suggests
that C≡C triple bond cleavage may be involved rather than C=C
double bond cleavage of 1a.
Since the different products were obtained in DMSO and 1,4-
dioxane, we envisioned that products 3 and 5 were generated from
a same intermediate. Then the possible intermediate 10 was
synthesized in THF under Ar and further investigated in control
experiments. Tryptophol product 3a was obtained in 70% yield in
the present of O2 (Eq. 8). Similarly, when 1,4-dioxane was
employed as solvent, peroxide tryptophol 5a was produced in
68% yield (Eq. 9). On the contrary, both of these reactions did not
work under Ar (Eqs 8-9). These results demonstrate that 10 may
be a possible intermediate for this novel transformation (for the
detection of 10 under Ar, and in-situ 1H NMR experiment, see SI).
In addition, 5a could be highly efficiently converted into 3a either
in the presence or absence of O2 in DMSO with the CH3SO2CH3
as the byproduct detected by GC-MS (Eq. 10, also see SI), which
indicates that DMSO can be a reductant to reduce the peroxide
tryptophol 5a to tryptophol 3a.
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Scheme 3. Proposed Mechanism.
To further understand the ring-opening mechanisms, styrenes
and TEMPO, which were proven to be efficient radical traps,
were allowed to react with 10 under Ar. The stryene-trapped
products 11a-b and TEMPO-trapped product 11c were obtained
in moderate yields (Eq. 11-12), which demonstrate a radical
pathway. Thus, homolytic cleavage of C-C bond of intermediate
10 followed by the O2-trapped process may be involved in this
transformation.
In summary, we have demonstrated a novel approach to tryp-
tophol derivatives synthesis through chemical bonds cleavage and
reassembly strategy. This metal-free oxygenation chemistry is
very easily operated using simple and readily available substrates
under mild conditions, and provides an efficient protocol for
complex and highly valuable tryptophol derivatives synthesis. The
mechanism is resonablly proposed and may promote the discovery
of new methodologies through C-C bond cleavage and dioxygen
activation.
On the basis of above preliminary results, the proposed
mechanism is illustrated in Scheme 3. Initially, enamine A is
quickly formed by hydroamination of 2a with 1a.16 Subsequently,
intramolecular thermal [2+2] cyclization17 occurs by heating to
form the key intermediate 10, which is highly reactive and easily
undergoes C-C bond homolytic cleavage to generate radical
intermediate B. And then the secondary carbon radical has
priority over the tertiary carbon radical to be trapped by O2
leading to peroxide radical intermediate C. Subsequent
intramolecular 1,5-hydrogen atom transfer (1,5-HAT) process18
enables the formation of peroxide tryptophol 5a, which could be
successfully obtained in 1,4-dioxane. Finally, the peroxide
tryptophol 5a is reducted by DMSO19 to generate tryptophol
ASSOCIATED CONTENT
Supporting Information. Experimental procedures, analytical
data for products, NMR spectra of products. This material is
available free of charge via the Internet at http://pubs.acs.org.
- 3 -
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 4 of 5
1
2
gorich, K. M.; Sigman, M. S. Angew. Chem., Int. Ed. 2006, 45, 6612. (e)
Shi, Z.; Zhang, C.; Tang, C.; Jiao, N. Chem. Soc. Rev. 2012, 41, 3381. (f)
Wu, W.; Jiang, H. Acc. Chem. Res. 2012, 45, 1736. (g) Campbell, A. N.;
Stahl, S. S. Acc. Chem. Res. 2012, 45, 851. (h) Allen, S. E.; Walvoord, R.
R.; Padilla-Salinas, R.; Kozlowski, M. C. Chem. Rev. 2013, 113, 6234. (i)
Wang, J.-R.; Deng, W.; Wang, Y.-F.; Liu, L.; Guo, Q.-X. Youji Huaxue
2006, 26, 397.
AUTHOR INFORMATION
3
4
5
6
7
8
9
Corresponding Author
jiaoning@pku.edu.cn.
(8) For selected recent examples, see: (a) Zhang, Y.-H.; Yu, J.-Q. J. Am.
Chem. Soc. 2009, 131, 14654. (b) Huang, X.; Li, X.; Zou, M.; Song S.;
Tang, C.; Yuan, Y.; Jiao, N. J. Am. Chem. Soc. 2014, 136, 14858. (c)
Zhang, C.; Jiao, N. J. Am. Chem. Soc. 2010, 132, 28. (d) Chiba, S.; Zhang,
L.; Lee, J.-Y. J. Am. Chem. Soc. 2010, 132, 7266. (e) Zhang, C.; Feng, P.;
Jiao, N. J. Am. Chem. Soc. 2013, 135, 15257. (f) Ling, F.; Li, Z.; Zheng,
C.; Liu, X.; Ma, C. J. Am. Chem. Soc. 2014, 136, 10914. (g) Wang, Z.-Q.;
Zhang, W.-W.; Gong, L-B.; Tang, R.-Y.; Yang, X.-H.; Liu, Y.; Li, J-H.
Angew. Chem. Int. Ed. 2011, 50, 8968. (h) Wang, H.; Wang, Y.; Liang,
D.; Liu, L.; Zhang, J.; Zhu, Q. Angew. Chem., Int. Ed. 2011, 50, 5678. (i)
Allpress, C. J.; Miłaczewska, A.; Borowski, T.; Bennett, J. R.; Tierney, D.
L.; Arif, A. M.; Berreau, L. M. J. Am. Chem. Soc., 2014, 136, 7821. (j) Su,
Y.; Sun, X.; Wu, G.; Jiao, N. Angew. Chem., Int. Ed., 2013, 52, 9808. (k)
Liu, Q. Wu, P.; Yang, Y.; Zeng, Z.; Liu, J.; Yi, H.; Lei, A.; Angew. Chem.,
Int. Ed., 2012, 51, 4666; (l) Chuang, G. J.; Wang, W.; Lee, E.; Ritter, T. J.
Am. Chem. Soc. 2011, 133, 1760. (m) Garcia-Bosch, I.; Company, A.;
Frisch, J. R.; Torrent-Sucarrat, M.; Cardellach, M.; Gamba, I.; Gꢀell, M.;
Casella, L.; Que, L.; Ribas, X., Jr.; Luis, J. M.; Costas, M. Angew. Chem.,
Int. Ed. 2010, 49, 2406. (n) Wang, A. Jiang, H. J. Am. Chem. Soc. 2008,
130, 5030. and references therein.
(9) (a) Piera, J.; Bäckvall, J.-E. Angew. Chem., Int. Ed. 2008, 47, 3506. (b)
Shapiro, N.; Kramer, M.; Goldberg, I.; Vigalok, A. Green Chem. 2010, 12,
582. (c) Lu, Q.; Zhang, J.; Wei, F.; Qi, Y.; Wang, H.; Liu, Z.; Lei, A. Angew.
Chem., Int. Ed. 2013, 52, 7156. (d) Wang, T.; Jiao, N. J. Am. Chem. Soc.
2013, 135, 11692. (f) Liang, Y.-F.; Jiao, N. Angew. Chem., Int. Ed. 2014, 53,
548. (e) Liu, H.; Dong, C.; Zhang, Z.; Wu, P.; Jiang, X. Angew. Chem. Int.
Ed. 2012, 51, 12570. (f) Hu, M.; Song, R.-J.; Li. J.-H. Angew. Chem. Int. Ed.
2015, 54, 608. (g) Handa, S.; Fennewald, J. C.; Lipshutz. B. H. Angew.
Chem. Int. Ed. 2014, 53, 3432. (h) Schmidt, V. A. Alexanian, E. J. Angew.
Chem. Int. Ed. 2010, 49, 4491. (i) Lara, M.; Mutti, F. G.; Glueck, S. M.;
Kroutil, W. J. Am. Chem. Soc. 2009, 131, 5368, and references therein.
(10) (a) Chau, T. T.; Walter, T.; Katz, A.; Weichman, B. M. Drug Dev.
Res. 1993, 28, 488. (b) Fernando, I. N.; Francis, P. L.; Smith, I. J. Neural.
Transm. 1983, 56, 33.
(11) Shi, Z.; Zhang, C.; Li, S.; Pan, D.; Ding, S.; Cui, Y.; Jiao, N.
Angew. Chem., Int. Ed. 2009, 48, 4572.
(12) Zhang, W.; Sun, M.; Salomon. R. G. J. Org. Chem. 2006, 71, 5607.
(13) Gupta, S. P. Progress in Drug Research 1995, 45, 67.
(14) Jiao, W.-H.; Gao, H.; Li, C-Y.; Zhou, G.-X.; Kitanaka, S.;
Ohmurae, A.; Yao, X.-S. Magn. Reson. Chem. 2010, 48, 490.
(15) King, F. D.; Jose Bermudez, S. D.; Sanger, G. J. J. Med. Chem.
1990, 33, 2944.
(16) For reviews, see: (a) Severin, R.; Doye, S. Chem. Soc. Rev. 2007,
36, 1407. (b) Pohlki, F.; Doye, S. Chem. Soc. Rev. 2003, 32, 104.
(17) (a) Brannock, K. C.; Bell, A.; Burpitt, R. D.; Kelly, C. A. J. Org.
Chem. 1964, 29, 801. (b) Ichihara, A.; Kimura, R.; Yamada, S.; Sakamu-
ra, S. J. Am. Chem. Soc. 1980, 102, 6353. (c) Sheldrake, H. M.; Wallace,
T. W.; Wilson, C. P. Org. Lett. 2005, 7, 4233.
ACKNOWLEDGMENT
Financial support from National Basic Research Program of Chi-
na (973 Program) (No. 2015CB856600), National Natural Sci-
ence Foundation of China (21325206, 21632001), and National
Young Top-notch Talent Support Program are greatly appreciated.
We thank Xiaojin Wen for reproducing the results of 3o and 5c,
Lingsheng Ai for reproducing the results of 3q and 5a.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
REFERENCES
(1) (a) Trost, B. M. Science, 1991, 254, 1471; (b) Newhouse, T.; Baran,
P. S.; Hoffmann, R.W. Chem. Soc. Rev., 2009, 38, 3010.
(2) For some reviews, see: (a) de Meijere, A. Chem. Rev. 2003, 103, 931.
(b) Rubin, M.; Rubina, M.; Gevorgyan, V. Chem. Rev. 2007, 107, 3117.
(c) Carson, C. A.; Kerr, M. A. Chem. Soc. Rev. 2009, 38, 3051. (d) Mura-
kami, M.; Matsuda, T. Chem. Commun. 2011, 47, 1100. (e) Seiser, T.;
Saget, T.; Tran, D. N.; Cramer, N. Angew. Chem., Int. Ed. 2011, 50, 7740.
(3) For reviews of C-C cleavage, see: (a) Crabtree, R. H. Chem. Rev.
1985, 85, 245. (b) Rybtchinski, B.; Milstein, D. Angew. Chem., Int. Ed.
1999, 38, 870. (c) Jun, C.-H. Chem. Soc. Rev. 2004, 33, 610. (d) Tobisu,
M.; Chatani, N. Chem. Soc. Rev. 2008, 37, 300. (e) Chen, F.; Wang, T.;
Jiao, N. Chem. Rev. 2014, 114, 8613. (f) Dermenci, A.; Coe, J. W.; Dong,
G. Org. Chem. Front. 2014, 1, 567. (g) Liu, H.; Feng, M.; Jiang, X. Chem.
Asian J. 2014, 9, 3360. (h) Souillart, L.; Cramer, N. Chem. Rev. 2015,
115, 9410.
(4) For selected recent examples, see: (a) Zhao, H.; Fan, X.; Yu, J.; Zhu
C. J. Am. Chem. Soc., 2015, 137, 3490. (b) Seiser, T.; Saget, T.; Tran, D.
N.; Cramer, N. Angew. Chem., Int. Ed. 2011, 50, 7740. (c) Xi, Z.; Sato,
K.; Gao, Y.; Lu, J.; Takahashi, T. J. Am. Chem. Soc. 2003, 125, 9568. (d)
Lei, Z.-Q.; Li, H.; Li, Y.; Zhang, X.-S.; Chen, K.; Wang, X.; Sun, J.; Shi,
Z.-J. Angew. Chem., Int. Ed. 2012, 51, 2690. (e) Wender, P. A.; Correa, A.
G.; Sato, Y.; Sun, R. J. Am. Chem. Soc. 2000, 122, 7815. (f) Li, H.; Li,
W.; Liu, W.; He, Z.; Li, Z. Angew. Chem., Int. Ed. 2011, 50, 2975. (g) He,
C.; Guo, S.; Huang, L.; Lei, A. J. Am. Chem. Soc. 2010, 132, 8273. (h)
Sugiishi, T.; Kimura, A.; Nakamura, H. J. Am. Chem. Soc. 2010, 132,
5332. (i) Shen, T.; Wang, T.; Qin, C.; Jiao, N. Angew. Chem., Int. Ed.
2013, 52, 6677. (j) Dreis, A. M.; Douglas, C. J. J. Am. Chem. Soc. 2009,
131, 412. (k) Tobisu, M.; Nakamura, R.; Kita, Y.; Chatani, N. J. Am.
Chem. Soc. 2009, 131, 3174. (l) Wang, J.; Chen, W.; Zuo, S.; Liu, L.;
Zhang, X.; Wang, J. Angew. Chem., Int. Ed. 2012, 51, 12334. (m) Yan,
H.; Wang, H.; Li, X.; Xin, X,; Wang, C.; Wan, B. Angew. Chem., Int. Ed.
2015, 54, 10613. (n) Zeng, R.; Dong, G. J. Am. Chem. Soc. 2015, 137,
1408. (o) Chiba, S. Xu, Y.-J.; Wang, Y.-F. J. Am. Chem.
Soc., 2009, 131, 12886, and references therein.
(5) For selected reviews on alkyne metathesis, see: (a) Fürstner, A.; Da-
vies, P. W. Chem. Commun. 2005, 2307. (b) Villar, H.; Marcus, F.; Bolm,
C. Chem. Soc. Rev. 2007, 36, 55.
(6) (a) Qin, C.; Su. Y.; Shen, T.; Shi, X.; Jiao, N. Angew. Chem., Int. Ed.
2016, 55, 350. (b) Tanaka, K.; Kamisawa, A.; Suda, T.; Noguchi, K.;
Hirano, M. J. Am. Chem. Soc. 2007, 129, 12078.
(7) For some reviews about aerobic oxidation and oxygenation reactions
with O2, see: (a) Punniyamurthy, T.; Velusamy, S.; Iqbal, J. Chem. Rev.
2005, 105, 2329. (b) Stahl, S. S. Angew. Chem., Int. Ed. 2004, 43, 3400.
(c) Sigman, M. S.; Jensen, D. R. Acc. Chem. Res. 2006, 39, 221. (d) Gli-
(18) Robertson, J.; Pillai, J.; Lush, R, K. Chem. Soc. Rev., 2001, 30, 94.
(19) Bloodworth, A. J; Melvin. J. Org. Chem. 1986, 51, 2612.
- 4 -
ACS Paragon Plus Environment

Page 5 of 5
Journal of the American Chemical Society
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
5
ACS Paragon Plus Environment