Copper-Catalyzed Cascade Radical Addition-Cyclization Halogen Atom Transfer between Alkynes and Unsaturated α-Halogenocarbonyls

Article abstract of DOI:10.1021/acscatal.6b03033

A Cu-catalyzed cascade radical addition/cyclization/halogen atom transfer between alkynes and α-halogeno-γ, δ-unsaturated carbonyl compounds for the synthesis of various substituted cyclopentenes is described. Since up to four Csp³-Csp² bonds, two Csp³-Br bonds, and two carbocycles can be established in a single reaction, this 100% atom-efficient reaction exhibits the advantages of wide substrate scope, high functional group tolerance, and step-economics, and it offers an entry of the atom transfer radical addition/cyclization (tandem ATRA-ATRC) process to the synthesis of substituted cyclopentenes.

Full text of DOI:10.1021/acscatal.6b03033

Subscriber access provided by UB + Fachbibliothek Chemie | (FU-Bibliothekssystem)
Letter
Copper-Catalyzed Cascade Radical Addition-Cyclization-Halogen Atom
Transfer between Alkynes and Unsaturated #-Halogenocarbonyls
Yuzhen Gao, Pengbo Zhang, Zhe Ji, Guo Tang, and Yu-Fen Zhao
ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.6b03033 • Publication Date (Web): 29 Nov 2016
Downloaded from http://pubs.acs.org on November 29, 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.
ACS Catalysis 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
ACS Catalysis
1
2
3
4
5
6
7
8
9
CopperꢀCatalyzed Cascade Radical AdditionꢀCyclizationꢀ
Halogen Atom Transfer between Alkynes and Unsaturated αꢀ
Halogenocarbonyls
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
Yuzhen Gao, Pengbo Zhang, Zhe Ji, Guo Tang,* and Yufen Zhao
Department of Chemistry, College of Chemistry and Chemical Engineering, and the Key Laboratory for Chemical Biology
of Fujian Province, Xiamen University, Xiamen, Fujian 361005, China.
Supporting Information Placeholder
ABSTRACT: A Cuꢀcatalyzed cascade radical addition/cyclization/halogen atom transfer between alkynes and αꢀhalogenoꢀγ, δꢀ
unsaturated carbonyl compounds for the synthesis of various substitutedꢀcyclopentenes is described. Since up to four Csp3ꢀCsp2
bonds, two Csp3ꢀBr bonds and two carbocycles can be established in a single reaction, this 100% atom efficient reaction exhibits
the advantages of wide substrate scope, high functional group tolerance and stepꢀeconomics and offers an entry of tandem ATRAꢀ
ATRC process to the synthesis of substitutedꢀcyclopentenes.
KEYWORDS: tandem ATRA-ATRC reaction, copper-catalyzed, carbon radical, cyclic systems, cyclopentenes
Practical and innovative methods to construct cyclic sysꢀ
tems continue to be an important area in modern organic
chemistry. Among all types of synthetic methods, freeꢀradical
cyclization is a powerful procedure for the formation of cyclic
systems by carbon–carbon bond formation, as it provides
unique routes leading to target molecules in the fewest and
concise steps.1
also been made in the intermolecular ATRA reactions between
alkyl halides and alkynes.14 Recently, Hu14a reported a Cuꢀ
catalyzed cisꢀselective carboiodination of terminal acetylenes
with functionalized alkyl iodides, which were generated by
treating alkyl bromides with KI (Scheme 1a). Soon after,
Scheme 1. CopperꢀCatalyzed Intermolecular ATRA of Alkyl
Atom transfer radical addition (ATRA) or cyclization
(ATRC) of haloalkanes and halocarbonyls to unsaturated
compounds serves as an atomꢀeconomical method of simultaꢀ
neously forming CꢀC and CꢀX bonds, which provide a convenꢀ
ient route to the construction of cyclic frameworks.2 In parꢀ
ticular, the products of ATRA and ATRC reactions retain halꢀ
ogen functionality which can be used in further synthesis.
ATRA and ATRC reactions have been reported with a range
of metal catalysts, such as ruthenium3, iron4, nickel5, palladiꢀ
um6 and iridium7. However, thus far copperꢀbased catalysts
have been the most commonly employed agents, that have
emerged as the mildest, most costꢀeffective and high yielding
strategy with which to synthesize various cyclic systems. 2b, 8ꢀ12
The application of copperꢀcatalyzed intramolecular ATRC
reactions to carbonꢀcarbon doubleꢀbond formation for the conꢀ
struction of γꢀlactams9, γꢀlactones10, cyclicꢀethers11 and pyrrolꢀ
idines12 are now reasonably well established. Yet, methods for
the synthesis of cyclic systems through intermolecular ATRC
process are lacking.7b, 13 As a result, the application scope of
ATRC has been restricted. Moreover, some progress has been
Halides to Alkynes
ACS Paragon Plus Environment

ACS Catalysis
Table 2. Scope of Alkynes a
Page 2 of 5
Table 1. Optimization of Reaction Conditions a
1
2
3
4
5
6
7
8
9
entry
1
[Cu]
ligand
L1
L1
L1
L1
L2
L3
L4
L4
ꢀ
base
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
ꢀ
solvent
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
DCE
yield (%)
Cu(OAc)2·H2O
CuBr2
13
32
30
42
8
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
2
3
CuBr
4
Cu(SO4)2·5H2O
Cu(SO4)2·5H2O
Cu(SO4)2·5H2O
Cu(SO4)2·5H2O
ꢀ
5
6
61
76
0
7
8
9
Cu(SO4)2·5H2O
Cu(SO4)2·5H2O
Cu(SO4)2·5H2O
Cu(SO4)2·5H2O
Cu(SO4)2·5H2O
Cu(SO4)2·5H2O
Cu(SO4)2·5H2O
Cu(SO4)2·5H2O
Cu(SO4)2·5H2O
8
10
11
12
13
14
15
16
17
L4
L4
L4
L4
L4
L4
L4
L4
6
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
Na2CO
Et3N
33b
67c
60
32
12
55
trace
DMF
DMSO
CH3CN
CH3CN
a Reaction conditions: 1 (0.3 mmol), 2a (0.45 mmol), Cu(SO4)2·5H2O (10
mol%), bpy (20 mol%) and K2CO3 (0.3 mmol) in CH3CN (2 mL) stirring
under argon in 80 oC for 10 h.
a
Reaction conditions: 1a (0.3 mmol), 2a (0.45 mmol), [Cu] (10 mol%),
ligand (20 mol%) and base (0.3 mmol) in solvent (2 mL) stirring under
b
alkyl halide,14d the reaction was inhibited in the absence of a
copper salt, ligand or base (entries 8–10). Moreover, the yield
of product 3a decreased when the temperature was lowered to
60 °C or raised to 100 °C (entries 11−12) indicating that the
choice of temperature is also important. Screening other solꢀ
vents, such as DCE, DMF, and DMSO revealed that MeCN
was the best choice (entries 13−15). The effect of base was
also investigated and K2CO3 was found to be the most suitable
base (entries 16−17). After a series of detailed investigations16,
we established an efficient route to substitutedꢀcyclopentenes
argon for 10 h. Oil bath temperature. Yield of the isolated product. 60
oC. c 100 oC
Zhu14b reported Cuꢀcatalyzed carbohalogenation of terminal
alkynes providing quaternaryꢀcarbonꢀcontaining and transꢀ
selective alkenyl halides (Scheme 1b). These procedures proꢀ
vide an efficient process by which to generate alkenyl halides,
which are important synthetic building blocks. Although seꢀ
quential atom transfer reactions have been developed8f,
,
15
there are few reports of tandem ATRAꢀATRC reactions beꢀ
tween alkyl halides and alkynes for the construction of cyclic
frameworks.7a Therefore, the development of new, efficient
methods for the intermolecular and tandem ATRAꢀATRC
reactions between alkyl halides and alkynes would be exꢀ
tremely valuable. Herein, we considered that 2ꢀ
halogenomalonate containing unsaturated functional groups
could react with alkynes via a intermolecular and tandem
ATRAꢀATRC process, leading to the construction of substiꢀ
tuted cyclopentenes (Scheme 1c).
via
a
Cuꢀcatalyzed intermolecular and sequential
ATRA/ATRC reactions. The optimal reaction conditions are:
1a (0.3 mmol), 2a (0.45 mmol), Cu(SO4)2·5H2O (10 mol% ),
L4 (20 mol% ), K2CO3 (0.3 mmol) and CH3CN (2.0 mL) at 80
°C for 10 h under a nitrogen atmosphere.
With the optimized reaction conditions in hand, we investiꢀ
gated the scope of this Cuꢀcatalyzed annulation by varying the
alkynes 1, and the results are summarized in Table 2. Various
functional groups on the benzene were examined and most
were tolerated under the optimized conditions. With methyl
substitution on benzene, these compounds reacted efficiently
to give the desired products (3b−3f) in 64−53% yields, indiꢀ
cating the position and the number of the substituent on the
benzene ring exerted a small influence. It is noteworthy that
when a large stericallyꢀhindered alkyne was employed, such as
2ꢀethynylꢀ1,3,5ꢀtrimethylbenzene (1e), the product 3f was
obtained in 53% yield. Some electronꢀdonating groups such as
ethyl, tert-butyl, phenyl and methoxy were investigated and
gave the corresponding products 3g−3j in 82−51% yields.
Halogen atoms such as fluoro, bromo, and chloro on the aroꢀ
matic ring were not affected under the present reaction condiꢀ
tions to afford the corresponding products 3k−3n in moderate
To test this hypothesis, ethynylbenzene (1a) and diethyl 2ꢀ
allylꢀ2ꢀbromomalonate (2a) were chosen as reaction partners
(Table 1). Initially, the reaction between 1a and 2a was conꢀ
ducted in MeCN. Using 10 mol% of Cu(OAc)2·H2O as the
catalyst, 20 mol% PMDTA (L1) as the ligand, and 1 equiv of
K2CO3 as the base, 3a was isolated in 13% yield, after being
o
heated at 80 C for 10 h (entry 1). Subsequently, various copꢀ
per salts were explored showing that Cu(SO4)2·5H2O was the
most effective and gave 3a in 42% yield (entries 1–4). Screenꢀ
ing other ligands, such as TMEDA (L2), 1,10ꢀphenanthroline
(L3) and bipy (L4), revealed that L4 was the best choice and
gave 3a in 76% yield (entries 5–7). Although Hu group reꢀ
ported that the base alone was sufficient to activate certain
ACS Paragon Plus Environment

Page 3 of 5
ACS Catalysis
could also react smoothly with 2a to afford the expected prodꢀ
Table 3. Scope of Unsaturated αꢀHalogenocarbonyl Comꢀ
pounds a
ucts 3v and 3w in 62% and 41% yields. Ethynylcyclopropane
was also examined but unfortunately only trace amounts of the
desired product 3x were detected.
1
2
3
Next, we turned our attention to exploring various unsaturated
αꢀhalogenocarbonyl compounds 2 under standard conditions
(Table 3). When the starting material 2b contains a termiꢀ
nal alkyne group, the desired vinylic bromide product 4a was
obtained in lower yield. Dimethyl 2ꢀallylꢀ2ꢀbromomalonate 2c
was also employed and resulted in the production of 4b–4d in
75–61% yields. By contrast, the phenacylꢀsubstituted counterꢀ
part 2d led to the corresponding products 4e–4f in lower yields
and gave 4aa as the byproduct, potentially due to the increased
steric hindrance. The reaction could be applied to other actiꢀ
vated organobromides, as exemplified by the construction of
4g and 4h. Unfortunately, an attempt to build cyclohexene
ring 4i or cyclopent ring with a quaternary carbon center 4j
was failed. When diethyl 2ꢀallylꢀ2ꢀchloromalonate 2h was
employed instead of 2a, chlorinated product 4k was syntheꢀ
sized successfully in a low yield. Gratifyingly, with diethyl 2ꢀ
allylꢀ2ꢀiodomalonate 2i acting as the carbohalogenation reaꢀ
gent, iodinated products 4l−4o were successfully obtained in
79−67% yields. An important extension of this protocol was
achieved by simply adding 2 equiv of KI to the standard conꢀ
ditions, the reaction between 1 and 2a produced 4l and 4m in
62% and 68% yields, thus allowing a more simple and practiꢀ
cal way to synthesize iodinated products.
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
Br
Br
Br
Br
MeO2C
MeO2C
MeO2C
MeO2C
MeO2C
MeO2C
EtO2C
EtO2C
S
4a
21%
4d 63%
Br
Me
Br
4c
61%
O
4b
75%
CN
Br
E : Z = 1:0.14
Br
O
EtO2C
Ac
Ph(O)C
Ph(O)C
Ph(O)C
Ph(O)C
Ph
Ph
4aab
4f
22%
4e 28%
F
4g
53% (dr = 1:0.6)
Cl
Br
EtO2C
Ac
EtO2C
EtO2C
Br
EtO2C
EtO2C
EtO2C
EtO2C
Br
Ph
mixture
Ph
4i
4k
11%
OMe
4j
Scheme 2 CuꢀCatalyzed Double Tandem ATRAꢀATRC Reacꢀ
tion
trace
OMe
I
4h
66% (dr = 1:0.7)
I
I
I
EtO2C
EtO2C
EtO2C
EtO2C
EtO2C
EtO2C
EtO2C
EtO2C
S
c
OMe
c
Br
l
4
72% (62%)
m
4
79% (68%)
4o 74%
4n 67%
a
Reaction conditions: 1 (0.3 mmol), 2 (0.45 mmol), Cu(SO4)2·5H2O (10
mol%), bpy (20 mol%) and K2CO3 (0.3 mmol) in CH3CN (2 mL) stirring
under argon in 80 C for 10 h. b the byproduct when 2d was employed as
o
c
the the carbohalogenation reagent. KI (0.6 mmol, 2.0 equiv) was added
to the reactions between 1 and 2a under standard conditions.
to good yields, thus providing ample opportunity for further
elaboration by the transition metalꢀcatalyzed crossꢀcoupling
reactions. Moreover, the structure of 3k was confirmed by Xꢀ
ray crystal structure analysis (Figure 1).17 Substrates bearing
electronꢀwithdrawing (COMe and CN) groups on the benzene
ring were also investigated and smoothly converted into prodꢀ
ucts 3o−3p in 56−52% yields. The process was extended to
substrate 1q, bearing an amino group, providing 3q in lower
yield. Gratifyingly, sterically hindered substrates with 2ꢀ
fluorenyl, 3,4ꢀmethylenedioxyphenyl, 2ꢀnaphthyl, 1ꢀnaphthyl
Scheme 3 Synthetic Utility of CuꢀCatalyzed Tandem ATRAꢀ
ATRC Reaction
Figure 1. Crystal structure of compound 3k.
also reacted with 2a efficiently to give the desired products
3r−3u in good yields. In addition, compounds with thienyl
Scheme 4 Radical Trapping Experiments
ACS Paragon Plus Environment

ACS Catalysis
Page 4 of 5
BHT could produce phenoxyl radical C which abstracts a hyꢀ
1
2
3
4
drogen atom through an intramolecular transfer to afford inꢀ
termediate D.20 Subsequently, intermediate D would react with
carbon radical A to afford product 7b. These results indicated
that the Cuꢀcatalyzed cascade reaction might proceed via a
radical mechanism.
5
On the basis of the aboveꢀmentioned experiments, we proꢀ
pose a tentative pathway for this transformation (Scheme 5).
Initially, the carbon radical A is formed by a SET process
from 2a, which then adds to 1a to give the alkenyl radical E.
The resulting alkenyl radical E participates in an intramolecuꢀ
lar radical substitution reaction to generate the intermediate F.
Subsequently, cationic intermediate G was formed through a
second SET between F and Cu(II) which ultimately was atꢀ
tacked by Brꢀ to afford product 3a (path a). Alternatively, the
carbon radical F directly react with [Cu]Br species to form the
desired product 3a (path b).
In conclusion, we have successfully developed a facile
method for the preparation of a broad spectrum of substitutedꢀ
cyclopentenes via Cuꢀcatalyzed tandem ATRAꢀATRC reacꢀ
tion between alkynes and αꢀhalogenoꢀγ, δꢀunsaturated carbonꢀ
yl compounds. Importantly, this transformation would provide
a new pathway for the formation of two Csp3ꢀCsp2 bonds and
one Csp3ꢀX bond in one step, highlighting the stepꢀeconomics
of this protocol. This method is highly efficient and a wide
range of functional groups are well tolerated under mild reacꢀ
tion conditions. Moreover, the use of an inexpensive
CuSO4·5H2O catalyst and readily available alkynes means that
this facile protocol will be attractive for academia and indusꢀ
try.
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
Scheme 5 A Tentative Mechanistic Pathway
ASSOCIATED CONTENT
Supporting Information
Remarkably, the oneꢀpot construction of dicyclopentenes 5a
and 5b were achieved by reacting alkynes 1aa and 1ab with
2a, respectively (Scheme 2). Although the yield appears to be
moderate, in view of the formation of four Csp3ꢀCsp2 bonds,
two Csp3ꢀBr bonds and two new carbocycles in a single reacꢀ
tion, it still represents a highly attractive method for the synꢀ
thesis of dicyclopentenes from readily accessible starting maꢀ
terials.
The synthetic utility of this reaction was explored, demonꢀ
strating the practical application of this method (Scheme 3). 1a
(10 mmol) was employed in a gramꢀscale reaction and affordꢀ
ed 4a in 74% yield. Epoxidation of 3a with metaꢀ
chloroperbenzoic acid (mꢀCPBA) gave 6a in 92% yield. Furꢀ
thermore, the reaction between 3a and diphenylphosphinothiꢀ
oic Sꢀacid gave 6b in 97% yield. We noted that dehydrohaloꢀ
genation of 3a would then yield a direct route to substitutedꢀ3ꢀ
methylenecyclopentꢀ1ꢀene 6c in 82% yield. It is noteworthy
that orangoazides have been widely used in medicinal chemisꢀ
try because of their versatile biological activities.18 And 6d
bearing an azide group was easily obtained from 3a in 80%
yield.
To gain insight into the reaction mechanism, preliminary
studies were carried out (Scheme 4). The reaction between 1a
and 2a was inhibited by adding 1.5 equiv of 2,2,6,6ꢀtetraꢀ
methylpiperidinooxy (TEMPO). Instead, 7a was formed in
71% yield (Scheme 4a). Based on literature precedents19, we
assume that the carbon radical A which is formed from 2a is
trapped by TEMPO to form intermediate B. With the assisꢀ
tance of another molecule of TEMPO, intermediate B underꢀ
goes elimination to form product 7a. Moreover, in the presꢀ
ence of butylated hydroxytoluene (BHT), no detectable 3a was
observed, and 7b was obtained in 55% yield (Scheme 4b).
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1039/x0xx00000x.
Experimental procedures for the synthesis, spectral data and
copies of 1H and 13C NMR spectra of all the products. (PDF)
Crystallographic data. ( CIF)
AUTHOR INFORMATION
Corresponding Author
*Eꢀmail: t12g21@xmu.edu.cn .
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENT
We thank NSFC (21232005, 21375113) and the National Basic
Research Program of China (2013CB910700), and the Fundamenꢀ
tal Research Funds for the Central Universities (20720160030).
We are grateful to Prof. Dr D. M. J. Lilley from University of
Dundee for valuable discussions on this paper.
REFERENCES
(1) (a) Bowman, W. R.; Bridge, C. F.; Brookes, P. J. Chem. Soc.
Perkin Trans. 1, 2000, 1–14. (b) Manoj, M.; Bora, U. RSC Adv. 2013,
3, 18716–18754. (c) Bowman, W. R.; Cloonan, M. O.; Krintel, S. L.
J. Chem. Soc. Perkin Trans. 1, 2001, 2885–2902. (d) Bowman, W. R.;
Fletcher, A. J.; Potts, G. B. S. J. Chem. Soc. Perkin Trans. 1, 2002,
2747–2762.
(2) For selected reviews on ATRC and ATRA reactions, see: (a)
Clark, A. J. Chem. Soc. Rev. 2002, 31, 1–11. (b) Clark, A. J. Eur. J.
Org. Chem. 2016, 2231–2243. (c) Studer, A.; Curran, D. P. Angew.
ACS Paragon Plus Environment

Page 5 of 5
ACS Catalysis
Chem. Int. Ed. 2016, 55, 58–102. (d) Matyjaszewski, K.; Xia, J. Chem.
Rev. 2001, 101, 2921–2990. (e) Pintauer, T.; Matyjaszewski, K. Chem.
Soc. Rev. 2008, 37, 1087–1097.
(12) (a) Udding, J. H.; Tuijp, C. K. J. M.; Hiemstra, H.; Speckamp,
W. N. Tetrahedron 1994, 50, 1907–1918. (b) Balili, M. N. C.; Pintauꢀ
er, T. Dalton Trans. 2011, 40, 3060–3066. (c) Ricardo, C.; Pintauer, T.
Chem. Commun. 2009, 3029–3031.
(13) (a) Iwamatsu, S.ꢀI.; Kondo, H.; Matsubara, K.; Nagashima, H.
Tetrahedron 1999, 55, 1687–1760. (b) Knorn, M.; Rawner, T.; Czerꢀ
wieniec, R.; Reiser, O. ACS Catal. 2015, 5, 5186–5193. (c) Nishikata,
T.; Noda, Y.; Fujimoto, R.; Sakashita, T. J. Am. Chem. Soc. 2013, 135,
16372–16375. (d) Arceo, E.; Montroni, E.; Melchiorre, P. Angew.
Chem. Int. Ed. 2014, 53, 12064–12068.
(14) For Cuꢀcatalyzed ATRA of alkyl halides to alkynes, see: (a)
Xu, T.; Hu, X. Angew. Chem. Int. Ed. 2015, 54, 1307–1311. (b) Che,
C.; Zheng, H.; Zhu, G. Org. Lett. 2015, 17, 1617–1620. (c) Tang, Y.;
Li, C. Org. Lett. 2004, 6, 3229–3231. (d) Xu, T.; Cheung, C. W.; Hu,
X. Angew. Chem. Int. Ed. 2014, 53, 4910–4914. (e) Wallentin, C.ꢀJ.;
Nguyen, J. D.; Finkbeiner, P.; Stephenson, C. R. J. J. Am. Chem. Soc.
2012, 134, 8875–8884. (f) Li, Z.; GarcíaꢀDomínguez, A.; Nevado, C.
Angew. Chem. Int. Ed. 2016, 55, 6938–6941. (g) Belhomme, M.ꢀC.;
Dru, D.; Xiong, H.ꢀY.; Cahard, D.; Besset, T.; Poisson, T.;
Pannecoucke, X. Synthesis 2014, 46, 1859–1870. (h) Lai, J.; Tian, L.;
Liang, Y.; Zhang, Y.; Xie, X.; Fang, B.; Tang, S. Chem. Eur. J. 2015,
21, 14328–14331.
(15) (a) MuñozꢀMolina, J. M.; Belderraín, T. R.; Pérez, P. J. Adv.
Synth. Catal. 2008, 350, 2365–2372. (b) Stevens, C. V.; Van Meenen,
E.; Masschelein, K. G. R.; Eeckhout, Y.; Hooghe, W.; D’hondt, B.;
Nemykin, V. N.; Zhdankin, V. V. Tetrahedron Lett. 2007, 48, 7108–
7111. (c) Helliwell, M.; Fengas, D.; Knight, C. K.; Parker, J.; Quayle,
P.; Raftery, J.; Richards, S. N. Tetrahedron Lett. 2005, 46, 7129–7134.
(16) See the Supporting Information for detailed data.
1
2
3
4
5
6
7
8
(3) (a) Severin, K. Chimia 2012, 66, 386–388. (b) Severin, K. Curr.
Org. Chem. 2006, 10, 217–224. (c) Nagashima, H.; Seji, K.; Ozaki,
N.; Wakamatsu, H.; Itoh, K.; Tomo, Y.; Tsuji, J. J. Org. Chem. 1990,
55, 985–990.
(4) (a) Dneprovskii, A. S.; Kasatochkin, A. N.; Boyarskii, V. P.;
Ermoshkin, A. A.; Yakovlev, A. A. Russ. J. Org. Chem. 2006, 42,
1120–1130. (b) De Campo, F.; Lastécouères, D.; Verlhac, J. B. J.
Chem. Soc. Perkin Trans. 1, 2000, 575–580.
(5) Boivin, J.; Yousfi, M.; Zard, S. Z. Tetrahedron Lett. 1994, 35,
5629–5632.
(6) (a) Liu, Q.; Chen, C.; Tong, X. Tetrahedron Lett. 2015, 56,
4483–4485. (b) Monks, B. M.; Cook, S. P. Angew. Chem. Int. Ed.
2013, 52, 14214–14218.
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
(7) (a) Gu, X.; Li, X.; Qu, Y.; Yang, Q.; Li, P.; Yao, Y. Chem. Eur.
J. 2013, 19, 11878–11882. (b) Nguyen, J. D.; Tucker, J. W.; Koniecꢀ
zynska, M. D.; Stephenson, C. R. J. J. Am. Chem. Soc. 2011, 133,
4160–4163.
(8) For recent reports on the Cuꢀcatalyzed intramolecular ATRA of
alkyl halides to C=C bonds, see: (a) Isse, A. A.; Vison, G.; Ghelfi, F.;
Roncaglia, F.; Gennaro, A. Adv. Synth. Catal. 2015, 357, 782–792.
(b) Bull, J. A.; Hutchings, M. G.; Quayle, P. Angew. Chem. Int. Ed.
2007, 46, 1869–1872. (c) De Paoli, P.; Isse, A. A.; Bortolamei, N.;
Gennaro, A. Chem. Commun. 2011, 47, 3580–3582. (d) Clark, A. J.;
Collis, A. E. C.; Fox, D. J.; Halliwell, L. L.; James, N.; O’ Reilly, R.
K.; Parekh, H.; Ross, A.; Sellars, A. B.; Willcock, H.; Wilson, P. J.
Org. Chem. 2012, 77, 6778–6788. (e) Sebren, L. J.; Devery III, J. J.;
Stephenson, C. R. J. ACS Catal. 2014, 4, 703–716. (f) Yang, D.; Yan,
Y.ꢀL.; Zheng, B.ꢀF.; Gao, Q.; Zhu, N.ꢀY. Org. Lett. 2006, 8, 5757–
5760.
(9) (a) Ram, R. N.; Kumar, N.; Singh, N. J. Org. Chem. 2010, 75,
7408–7411. (b) Motoyama, Y.; Kamo, K.; Yuasa, A.; Nagashima, H.
Chem. Commun. 2010, 46, 2256–2258. (c) Clark, A. J.; Battle, G. M.;
Bridge, A. Tetrahedron Lett. 2001, 42, 1999–2001.
(10) (a) De Campo, F.; Lastécouères, D.; Vinccent, J.ꢀM.; Verlhac,
J.ꢀB. J. Org. Chem. 1999, 64, 4969–4971. (b) Felluga, F.; Forzato, C.;
Ghelfi, F.; Nitti, P.; Pitacco, G.; Pagnoni, U. M.; Roncaglia, F. Tetra-
hedron: Asymmetry 2007, 18, 527–536. (c) Chen, V. X.; Boyer, F.ꢀD.;
Rameau, C.; Pillot, J.ꢀP.; Vors, J.ꢀP.; Beau, J.ꢀM. Chem. Eur. J. 2013,
19, 4849–4857.
(17) CCDC 1505770 (3k) contains the supplementary crystalloꢀ
graphic data for this paper. See the Supporting Information for details.
(18) (a) Hennessy, E. T.; Betley, T. A. Science 2013, 340, 591–595.
(b) Sun, X.; Li, X.; Song, S.; Zhu, Y.; Liang, Y. F.; Jiao, N. J. Am.
Chem. Soc. 2015, 137, 6059–6066. (c) Huryn, D. M.; Okabe, M.
Chem. Rev. 1992, 92, 1745–1768.
(19) (a) Jie, X.; Shang, Y.; Zhang, X.; Su, W. J. Am. Chem. Soc.
2016, 138, 5623–5633. (b) Maity, S.; Naveen, T.; Sharma, U.; Maiti,
D. Org. Lett. 2013, 15, 3384–3387. (c) Gui, Q.; Hu, L.; Chen, X.; Liu,
J.; Tan, Z. Chem. Commun. 2015, 51, 13922–13924.
(20) (a) Egami, H.; Ide, T.; Kawato, Y.; Hamashima, Y. Chem.
Commun. 2015, 51, 16675–16678. (b) Gao, Y.; Lu, G.; Zhang, P.;
Zhang, L.; Tang, G.; Zhao, Y. Org. Lett. 2016, 18, 1242–1245.
(11) (a) Udding, J. H.; Hiemstra, H.; Van Zanden, M. N. A.;
Speckamp, W. N. Tetrahedron Lett. 1991, 32, 3123–3126. (b) Ram,
R. N.; Charles, I. Chem. Commun. 1999, 2267–2268.
ACS Paragon Plus Environment