Enantioselective Trifluoromethylalkynylation of Alkenes via Copper-Catalyzed Radical Relay

Article abstract of DOI:10.1021/jacs.8b07436

A novel enantioselective copper-catalyzed trifluoromethylalkynylation of styrenes, proceeding through a radical relay process, is described herein, which affords structurally diverse CF₃-containing propargylic compounds in good yield with excellent enantioselectivities under very mild conditions. In addition, the reaction features wide substrate scope and good functional group tolerance. Moreover, the trifluoromethylalkynylated products can be easily converted into synthetically useful chiral terminal alkynes, allenes, Z-alkenes, as well as CF₃-modified nonsteroidal anti-inflammatory drugs.

Full text of DOI:10.1021/jacs.8b07436

Subscriber access provided by THOMAS JEFFERSON UNIV
Communication
Enantioselective Trifluoromethylalkynylation
of Alkenes via Copper-Catalyzed radical relay
Liang Fu, Song Zhou, Xiaolong Wan, Pinhong Chen, and Guosheng Liu
J. Am. Chem. Soc., Just Accepted Manuscript • Publication Date (Web): 22 Aug 2018
Downloaded from http://pubs.acs.org on August 22, 2018
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 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 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.
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
9
Enantioselective Trifluoromethylalkynylation of Alkenes via Copper-
Catalyzed Radical Relay
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
Liang Fu,a Song Zhou,b Xiaolong Wan,a Pinhong Chen,a and Guosheng Liu*a
a State Key Laboratory of Organometallic Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of
Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China
b School of Biotechnology and Health Science, Wuyi University, Jiangmen, 529020, China
Supporting Information Placeholder
ABSTRACT:
A
novel enantioselective copper-catalyzed
trifluoromethylalkynylation of styrenes, proceeding through a
radical relay process, is described herein, which affords
structurally diverse CF3-containing propargylic compounds in
good yield with excellent enantioselectivities under very mild
conditions. In addition, the reaction features wide substrate scope
and good functional group tolerance. Moreover, the
trifluoromethylalkynylated products can be easily converted into
synthetically useful chiral terminal alkynes, allenes, Z-alkenes, as
well as CF3-modified nonsteroidal anti-inflammatory drugs.
Molecules bearing a propargylic stereocenter are frequently found
in a myriad of natural products and therapeutics, such as
Efavirenz and AMG 837 (Scheme 1A).1 Meanwhile, chiral
alkynes have also been recognized as an important and useful
synthon in organic synthesis.1 Therefore, organic chemists made
considerable effort to develop methodologies for their synthesis
during the last several decades. Among them, catalytic
asymmetric alkynylation of alkenes serves as one of the most
efficient and prevalent tools.1c,2 Nevertheless, the asymmetric
alkynylation of alkenes has been less developed, only catalytic
enantioselective hydroalkynylation of alkenes has been
documented to date,3,4 where in situ generated chiral
organometallic acetylides int-I as a key intermediate underwent
asymmetric addition across alkenes, leading to the formation of a
propargylic stereocenter in the intermediate int-II (Scheme 1B).
Scheme 1. Catalytic asymmetric alkynylation of alkenes.
makes this asymmetric alkynylation of alkenes extremely difficult.
To the best of our knowledge, no such asymmetric alkynylation
reaction has been reported to date.
As our continuous research interest in asymmetric radical
transformations (ARTs),8 our group has developed a copper-
catalyzed radical relay process for the enantioselective cyanation9
and arylation10 of styrenes or benzylic C-H bonds, using TMSCN
and ArB(OH)2 as nucleophiles.11 Critical to the success of the
copper-catalyzed radical relay process is that a benzylic radical
intermediate is enantioselectively trapped by (L*)CuII(CN)2 or
Herein, we communicate
a novel enantioselective copper-
catalyzed alkynylation of styrenes through a radical relay process,
which involves a benzylic radical intermediate trapped by chiral
L*CuII-alkynyl species (Scheme 1C).
Given that the incorporation of the trifluoromethyl group into
pharmaceuticals and agricultural chemicals has a significant effect
on their properties, the exploration of trifluoromethylation
reactions has received much attention.5 Very recently, the Li6a and
Yu6b groups independently reported an intermolecular radical
trifluoromethylalkynylation of alkenes by employing electrophilic
alkynylating reagents (alkynyl-SO2CF3 or alkynyl-Ts) under
metal-free conditions.6 Meantime, the Zhu7a-b and Studer7c groups
have demonstrated the intramolecular trifluoromethylalkynylation
of alkenes, in which a Csp3-Csp bond was forged through
sequential carbon-centered radical addition to the C-C triple bond
and -elimination of the resultant vinyl radicals. Despite these
advances, the involvement of highly reactive radical species
(L*)CuII-Ar; in addition,
a
highly reactive (L*)Cu(III)
intermediate was proposed for the formation of Csp3-CN or Csp3-
Ar bonds through enantioselective reductive elimination.9-12
Therefore, we reasoned that, if nucleophilic alkynylating reagents
were suitable for the copper-catalyzed radical relay process, the
enantioselective alkynylation of styrenes would be feasible
(Scheme 1C).
Based on this hypothesis, several nucleophilic alkynylating
reagents 2a-2e were tested for the reaction of 4-bromostyrene 1a
with Tongi-I reagent in DCE/DMA (v/v = 1:1), using 10 mol%
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 2 of 5
1
2
3
4
5
6
7
8
Cu(CH3CN)4PF6 and 12 mol% bisoxazoline (Box) ligand L1. As
As shown in Table 2, styrenes bearing both electron-donating and
electron-withdrawing groups at the para position were suitable for
the reaction, giving the corresponding products 3a-3l in moderate
to good yields (46-88%) with excellent enantioselectivities (91-
97% ee). Notably, reactions of electron-rich styrenes 1d-1f and 1i
in a mixed solvent (DCE:DMA, v/v = 40:1) generally yielded the
desired products in slightly higher yields. In addition, reactions of
meta-substituted styrenes also worked well to provide the desired
products 3m-3o in good yields (62-72%) with excellent
enantioselectivities (88-95% ee). Furthermore, the substrate (1p)
bearing two substituents on the aromatic ring reacted smoothly
with 2a to afford the desired product 3p in 70% yield with 90% ee,
and the aryl framework of styrenes can be extended to a
naphthalene-derived system (3q 52%, 93% ee). Notably, various
functional groups such as halogen, ether, ester and nitrile were
well tolerated; in addition, benzyl chloride (1g) that is very prone
to atom-transfer radical processes was also compatible with the
radical relay process. The asymmetric trifluoromethylalkynylation
reaction is also scalable, the reaction of 1a could be performed on
a 5-mmol scale to give 1.42g the desired product 3a in 82% yield
with 92% ee.
Importantly, reactions of vinylheteroarenes worked nicely to
afford the desired enantiomerically enriched propargylic products
3r-3y in good yields (53-81%) with excellent enantioselectivities
(88-95% ee); notably, heterocycles commonly existing in
therapeutics, such as 1,2,4-triazoles, pyrazoles, indole, quinoline,
pyrrole, pyridine and thiophene, were well tolerated under the
current conditions, which once again showcased the robustness of
our method. More importantly, structural variations in the
alkynylating reagents 2 were also realized. As revealed in Table 2,
substituents on the C-C triple bond can be various alkyl (e.g., nBu,
tBu, methoxymethyl) and aryl groups, and all these alkynylating
reagents 2 exhibited good reactivity to afford the desired products
4a-4j in good yields (46-78%) with excellent enantioselectivities
(86-92% ee).
shown in Table 1A, disilyl-substituted acetylene 2a proved to be a
suitable reactant for the alkynylation reaction, giving the desired
product 3a in 89% yield, albeit with low enantioselectivity (33%
ee, entry 1). Notably, the reaction exclusively occurred at the
trimethoxysilyl position, with the trimethylsilyl group preserved,
suggesting that an alkynyl-Si(OMe)3 bond is more reactive than
alkynyl-SiMe3 bonds, with respect to transmetallation furnishing a
key (L*)Cu(II)-alkynyl intermediate. In fact, the alkynylsilyl
reagent 2b was unsuitable for this reaction (entry 2). Additionally,
alkynyl boron reagents 2c and 2d were also surveyed, but proved
to be ineffective (entry 3). Terminal alkyne 2e, a commonly-used
alkynylating reagent, didn't deliver the desired product either
(entry 4). Moreover, other elelctrophilic trifluoromethyl reagents,
such as Togni-II and Umemoto reagent, were also examined,
which couldn't promote the reaction (entries 5-6). Inspired by
these results, a series of chiral Box ligands were then investigated
(Table 1B). Compared to L1, the Box ligands L2 without gem-
substitutent and L3 with gem-7-membered ring gave the product
3a in worse yield, but with better enantioselectivities. The gem-
disubstituted ligands L4 and L5 gave similar results as L3. To our
delight, when the sterically bulkier ligand L6 was employed, the
reaction proceeded smoothly to give 3a in 83% yield with 92% ee.
The enantioselectivity of 3a could be further improved to 95% ee
using less amounts of DMA (DCE/DMA v/v from 1:1 to 7:1),
however, but with a significantly diminished yield (54%).
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
Table 1. Optimization of the reaction conditions.a
Scheme 2. Synthetic applications.
Reaction conditions: (a) NH4F (8.0 equiv.) in MeOH, room
temperature, 24 h. (b) CuTc (10 mol%) in toluene, room
temperature, 4 h. (c) TBD (20 mol%) in THF, room temperature,
48 h. (d) DIBAL-H (5.0 equiv.) in Et2O, 40 oC, 24 h. (e) RuCl3 (5
After having established the optimal reaction conditions, we
then investigated the substrate scope of this asymmetric reaction.
mol%), NaIO4 (4.0 equiv.) in
a
mixed solvent of
CCl4/CH3CN/H2O (v/v/v = 2:2:3), room temperature, 2 h.
ACS Paragon Plus Environment

Page 3 of 5
Journal of the American Chemical Society
1
2
Table 2. Substrate scope.a,b
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
To demonstrate the synthetic utility of our method, further
transformations of the trifluoromethylalkynylation products were
surveyed (Scheme 2). Upon treatment of 3a with ammonium
fluoride, the TMS group in 3a was successfully removed to afford
the oxidation of the C-C triple bond in the products 3e and 3p
gave the enantiomerically enriched CF3-modified Ibuprofen 9 and
Flurbiprofen 10 in good yield (89% and 84%) without loss of
enantioselectivity (95% ee and 91% ee).15
the terminal alkyne
5 in 87% yield without loss of
To provide some insight into the plausible radical mechanism
for this novel trifluoromethylalkynylation reaction, TEMPO as a
radical scavenger was subjected to our standard conditions. As we
expected, the reaction was significantly inhibited; in addition,
both CF3 radical and benzylic radicals were trapped by TEMPO
to give the products 11 and 12 (eq 1). Moreover, the ring-opening
product 14 was obtained in the reaction of radical clock substrate
13 (eq 2).
enantioselectivity, and the compound 5 could be further converted
to 1-sulfonyl-1,2,3-triazole 6 in 84% yield with 91% ee by click
reaction,13 by which the absolute configuration of the products
(R)-3 and (R)-4 was unambiguously determined. Notably, the
product 4e (91% ee) was isomerized to allene 7 in 95% yield with
89% ee by employing triazabicyclodecene (TBD) as catalyst.14
Moreover, the C-C triple bond in 3f was selectively reduced by
diisobutylaluminium hydride (DIBAL-H) to deliver Z-alkene 8 in
97% yield with 93% ee. More importantly, for nonsteroidal anti-
inflammatory drugs, e.g. high-profile Ibuprofen and Flurbiprofen,
In conclusion, we have developed the first enantioselective
copper-catalyzed trifluoromethylalkynylation of styrenes via a
radical relay process, which provides an easy access to the
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 4 of 5
1
2
3
4
Angew. Chem. Int. Ed. 2010, 49, 3827. (g) Chen, Z.-M.; Nervig, C. S.;
DeLuca, R. J.; Sigman, M. S. Angew. Chem. Int. Ed. 2017, 56, 6651. (h)
Koradin, C.; Polborn, K.; Knochel, P. Angew. Chem. Int. Ed. 2002, 41,
2535.
(4) For selected examples of asymmetric hydroalkynylation of electron-
deficient alkenes, see: (a) Zhi, Y. L.; Huang, J. H.; Liu, N.; Lu, T.; Dou, X.
W. Org. Lett. 2017, 19, 2378. (b) Dou, X. W.; Huang, Y. H.; Hayashi, T.
Angew. Chem. Int. Ed. 2016, 55, 1133. (c) Blay, G.; Cardona, L.; Pedro, J.
R.; Sanz-Marco, A. Chem. Eur. J. 2012, 18, 12966. (d) Yazaki, R.;
Kumagai, N.; Shibasaki, M. J. Am. Chem. Soc. 2010, 132, 10275. (e)
Fillion, E.; Zorzitto, A. K. J. Am. Chem. Soc. 2009, 131, 14608. (f)
Nishimura, T.; Sawano, T.; Hayashi, T. Angew. Chem. Int. Ed. 2009, 48,
8057. (g) Nishimura, T.; Guo, X.-X.; Uchiyama, N.; Katoh, T.; Hayashi, T.
J. Am. Chem. Soc. 2008, 130, 1576. (h) Knoepfel, T. F.; Zarotti, P.;
Ichikawa, T.; Carreira, E. M. J. Am. Chem. Soc. 2005, 127, 9682. (i) Kwak,
Y. S.; Corey, E. J. Org. Lett. 2004, 6, 3385.
(5) For reviews on trifluoromethylation of alkenes, please see: (a) Lan, X.-
W.; Wang, N.-X.; Xing, Y. L. Eur. J. Org. Chem. 2017, 5821. (b) Merino,
E.; Nevado, C. Chem. Soc. Rev. 2014, 43, 6598. (c) Egami, H.; Sodeoka,
M. Angew. Chem. Int. Ed. 2014, 53, 8294. (d) Zhang, C. ARKIVOC 2014,
453. (e) Chen, P. H.; Liu, G. S. Synthesis 2013, 45, 2919.
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
structurally diverse and enantiomerically enriched CF3-containing
propargylic products. In addition, the reaction features wide
substrate scope and high functional group tolerance. Moreover,
the trifluoromethylalkynylation products can be easily converted
into very useful chiral terminal alkynes, allenes, Z-alkenes and
carboxylic acids. Enantioselective trapping of a benzylic radical
with chiral (Box)CuII-alkynyl species is a key step for the
construction of a propargylic stereocenter. Further expansion of
this strategy is still in progress in our laboratory.
(6) (a) Zhou, S. F.; Song, T.; Chen, H.; Liu, Z. L.; Shen, H. G.; Li, C. Z.
Org. Lett. 2017,19, 698. (b) Jiang, H.; He, Y. Y.; Cheng, Y. Z.; Yu, S. Y.
Org. Lett. 2017, 19, 1240. (c) Gong, J. C.; Fuchs, P. L. J. Am. Chem. Soc.
1996, 118, 4486.
ASSOCIATED CONTENT
(7) (a) Liu, J.; Li, W. P.; Xie, J.; Zhu, C. J. Org. Chem. Front. 2018, 5,
797. (b) Xu, Y.; Wu, Z.; Jiang, J. X.; Ke, Z. F.; Zhu, C. Angew. Chem. Int.
Ed. 2017, 56, 4545. (c) Tang, X. J.; Studer, A. Chem. Sci. 2017, 8, 6888.
(8) For recent highlights on ARTs reactions, please see: (a) Lu, Q. Q.;
Glorius, F. Angew. Chem. Int. Ed. 2017, 56, 49. For selected examples,
see: (b) Kainz, Q. M.; Matier, C. D.; Bartoszewicz, A.; Zultanski, S. L.;
Peters, J. C.; Fu, G. C. Science 2016, 351, 681. (c) Cheng, Y.-F.; Dong,
X.-Y.; Gu, Q.-S.; Yu, Z.-L.; Liu, X.-Y. Angew. Chem. Int. Ed. 2017, 56,
8883. (d) Zhu, R.; Buchwald, S. L. J. Am. Chem. Soc. 2015, 137, 8069. (e)
Zhu, R.; Buchwald, S. L. Angew. Chem. Int. Ed. 2013, 52, 12655. (f)
Wang, F.-L.; Dong, X.-Y.; Lin, J.-S.; Zeng, Y.; Jiao, G.-Y.; Gu, Q.-S.;
Guo, X.-Q.; Ma, C.-L.; Liu, X.-Y. Chem 2017, 3, 979. (g) Lin, J.-S.; Dong,
X.-Y.; Li, T.-T.; Jiang, N.-C.; Tan, B.; Liu, X.-Y. J. Am. Chem. Soc. 2016,
138, 9357.
(9) (a) Wang, F.; Wang, D.; Wan, X.; Wu, L.; Chen, P.; Liu, G. J. Am.
Chem. Soc. 2016, 138, 15547. (b) Wang, D.; Wang, F.; Chen, P.; Lin, Z.;
Liu, G. Angew. Chem. Int. Ed. 2017, 56, 2054. (c) Wang, D.; Zhu, N.;
Chen, P.; Lin, Z.; Liu, G. J. Am. Chem. Soc. 2017, 139, 15632.
(10) (a) Wu, L.; Wang, F.; Wan, X.; Wang, D.; Chen, P.; Liu, G. J. Am.
Chem. Soc. 2017, 139, 2904. (b) Wang, D.; Wu, L.; Wang, F.; Wan, X.;
Chen, P.; Lin, Z.; Liu, G. J. Am. Chem. Soc. 2017, 139, 6811. For a
racemic reaction, see: (c) Wang, F.; Wang, D. H.; Mu, X.; Chen, P.; Liu,
G. J. Am. Chem. Soc. 2014, 136, 10202.
(11) (a) Zhang, W.; Wang, F.; McCann, S. D.; Wang, D.; Chen, P.; Stahl,
S. S.; Liu, G. Science 2016, 353, 1014. For racemic C-H bond arylation,
see: (b) Zhang, W.; Chen, P.; Liu, G. J. Am. Chem. Soc. 2017, 139, 7709.
(12) For pioneering studies on the Ni-catalyzed asymmetric cross-
coupling reactions involving carbon-centered radicals trapped by Ni(II)
intermediates, see: (a) Fu, G. C. ACS Cent. Sci. 2017, 3, 692. For selected
examples, see: (b) Fischer, C.; Fu, G. C. J. Am. Chem. Soc. 2005, 127,
4594. (c) Binder, J. T.; Cordier, C. J.; Fu, G. C. J. Am. Chem. Soc. 2012,
134, 17003. (d) Do, H.-Q.; Chandrashekar, E. R. R.; Fu, G. C. J. Am.
Chem. Soc. 2013, 135, 16288. (e) Schley, N. D.; Fu, G. C. J. Am. Chem.
Soc. 2014, 136, 16588. For other metal-catalyzed reactions, see: (f) Mao, J.
Y.; Liu, F. P.; Wang, M.; Wu, L.; Zheng, B.; Liu, S. Z.; Zhong, J. C.; Bian,
Q. H.; Walsh, P. J. J. Am. Chem. Soc. 2014, 136, 17662. (g) Cherney, A.
H.; Reisman, S. E. J. Am. Chem. Soc. 2014, 136, 14365. (h) Jin, M.; Adak,
L.; Nakamura, M. J. Am. Chem. Soc. 2015, 137, 7128. (i) Ding, W.; Lu,
L.-Q.; Zhou, Q.-Q.; Wei, Y.; Chen, J.-R.; Xiao, W.-J. J. Am. Chem. Soc.
2017, 139, 63.
Experimental procedures and characterization data. This material
is available free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
gliu@mail.sioc.ac.cn
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENT
We are grateful for financial support from the National Basic
Research Program of China (973-2015CB856600), the National
Nature Science Foundation of China (Nos. 21532009, 21672236
21790330 and 21761142010), the Science and Technology
Commission of Shanghai Municipality (Nos. 17XD1404500 and
17JC1401200), and the strategic Priority Research Program (No.
XDB20000000) and the Key Research Program of Frontier
Science (QYZDJSSW-SLH055) of the Chinese Academy of
Sciences. This research was partially supported by CAS
Interdisciplinary Innovation Team.
REFERENCES
(1) (a) Stang, P. J.; Diederich, F. Modern Acetylene Chemistry, Wiley-
VCH, Weinheim, 1995. (b) Diederich, F.; Stang, P. J.; Tykwinski, R. R.
Acetylene Chemistry: Chemistry, Biology, and Material Science, Wiley-
VCH, Weinheim, 2005. (c) Trost, B. M.; Li, C.-J. Modern Alkyne
Chemistry: Catalytic and Atom-Economic Transformations, Wiley-VCH,
New York, 2014.
(2) For a recent review on catalytic enantioselective hydroalkynylation of
alkenes, please see: Wang, Z.-X.; Bai, X.-Y.; Li, B.-J. Synlett 2017, 28,
509.
(3) For catalytic enantioselective hydroalkynylation of alkenes using
transition metal catalysts, see: (a) Bai, X.-Y.; Zhang, W.-W.; Li, Q.; Li,
B.-J. J. Am. Chem. Soc. 2018, 140, 506. (b) Bai, X.-Y.; Wang, Z.-X.; Li,
B.-J. Angew. Chem. Int. Ed. 2016, 55, 9007. (c) Fan, B. M.; Xu, J. B.;
Yang, Q. J.; Li, S. F.; Chen, H. L.; Liu, S. S.; Yu, L.; Zhou, Y. Y.; Wang,
L. Org. Lett. 2013, 15, 5956. (d) Sawano, T.; Ou, K. Y.; Nishimura, T.;
Hayashi, T. Chem. Commun. 2012, 48, 6106. (e) Fan, B.-M.; Yang, Q.-J.;
Hu, J.; Fan, C.-L.; Li, S.-F.; Yu, L.; Huang, C.; Tsang, W. W.; Kwong, F.
Y. Angew. Chem. Int. Ed. 2012, 51, 7821. (f) Shirakura, M.; Suginome, M.
(13) Raushel, J.; Fokin, V. V. Org. Lett. 2010, 12, 4952.
(14) Cui, X.-Y.; Ge, Y.-C.; Tan, S. M.; Jiang, H.; Tan, D.; Lu, Y. P.; Lee,
R.; Tan, C.-H. J. Am. Chem. Soc. 2018, 140, 8448.
(15) (a) An, D. K.; Okamoto, S.; Sato, F. Tetrahedron Lett. 1998, 39, 4555.
(b) Carlsen, P. H. J.; Katsuki, T.; Martin, V. S.; Sharpless, K. B. J. Org.
Chem. 1981, 46, 3936.
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