Copper-Catalyzed Divergent Trifluoromethylation/Cyclization of Unactivated Alkenes

Article abstract of DOI:10.1002/adsc.201500965

Most of the precedent copper-catalyzed trifluoromethylation reactions of unactivated alkenes concern terminal alkenes, and these processes are terminated in elimination, or nucleophilic addition, or semipinacol rearrangement, or C-H bond functionalization steps. In this study, we develop a trifluoromethylation method for both unactivated terminal and internal alkenes to enable divergent late-stage radical cyclization and achieve high molecular complexity. These cyclizations are well consistent with Baldwin's rule. Furthermore, a kinetic isotope effect (KIE) study and control reactions were conducted, and a plausible mechanism is proposed.

Full text of DOI:10.1002/adsc.201500965

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DOI: 10.1002/adsc.201500965
Copper-Catalyzed Divergent Trifluoromethylation/Cyclization of
Unactivated Alkenes
Jing Zheng,a Ziyang Deng,a Yan Zhang,a and Sunliang Cuia,*
a
Institute of Drug Discovery and Design, College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road,
Hangzhou, Zhejiang 310058, Peopleꢀs Republic of China
Fax: (+86)-571-8898-1456; e-mail: slcui@zju.edu.cn
Received: October 16, 2015; Revised: November 16, 2015; Published online: February 11, 2016
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201500965.
Abstract: Most of the precedent copper-catalyzed tri- stage radical cyclization and achieve high molecular
fluoromethylation reactions of unactivated alkenes complexity. These cyclizations are well consistent
concern terminal alkenes, and these processes are with Baldwinꢀs rule. Furthermore, a kinetic isotope
terminated in elimination, or nucleophilic addition, effect (KIE) study and control reactions were con-
À
or semipinacol rearrangement, or C H bond func- ducted, and a plausible mechanism is proposed.
tionalization steps. In this study, we develop a tri-
fluoromethylation method for both unactivated ter- Keywords: divergent synthesis; heterocycles; radi-
minal and internal alkenes to enable divergent late- cals; trifluoromethylation; unactivated alkenes
Introduction
pendently developed a trifluoromethylation of unacti-
vated alkenes to enable the semipinacol rearrange-
Trifluoromethylated compounds have gained much at- ment (Scheme 1c).[11] Very recently, Liu and Tan re-
tention in pharmaceuticals and agrochemicals, be- ported an interesting C H bond functionalization
À
cause carbon-fluorine bonds dramatically change the method triggered by a CF3 radical addition onto unac-
physical and biological properties of organic mole- tivated alkenes (Scheme 1d).[12] Despite these ad-
cules, such as metabolic stability, binding selectivity vancements in this field, the development of trifluoro-
and lipophilicity.[1] As a consequence, numerous methylation of both unactivated terminal and internal
methods to incorporate the CF3 group into organic alkenes, and sequential late-stage divergent radical
molecules have been reported.[2,3] Recently, transition cyclization to achieve high molecular complexity re-
metal-catalyzed trifluoromethylation of alkenes have mains interesting.[13]
emerged as a powerful and distinct method for form-
3
À
ing CF3 C(sp ) bonds. For example, Liu and Nevado
have respectively established novel trifluoromethyla- Results and Discussion
tion protocols for activated alkenes to construct CF3-
containing heteocycles.[4]
In continuation of our efforts in heterocycles synthe-
With regard to unactivated alkenes, Buchwald,[5] sis,[14] we envisioned that the copper-catalyzed tri-
Wang,[6] Fu,[7] Liu,[8] Sodeoka,[9] independently report- fluoromethylation of unactivated alkenes could gener-
ed that in the presence of a Cu catalyst, Togniꢀs re- ate secondary alkyl radicals, which can be coupled
agent or Umemotoꢀs reagent can react with unactivat- with a late-stage radical cyclization leading to novel
ed terminal alkenes and transfer a CF3 group to the heterocyclic structures. Herein, we describe a copper-
terminal position through a radical pathway. The re- catalyzed divergent trifluotrifluoromethylation/cycli-
sulting secondary radical or carbon cationic inter- zation of unactivated alkenes (Scheme 1e). The versa-
mediate can undergo elimination to terminate the tility of this strategy is highlighted by an expedient
process (Scheme 1a) or subsequently be trapped by synthesis of CF3-substituted 4-quinazolinones and di-
a nucleophile (Scheme 1b). On the other hand, hydroisoquinolinones including natural alkaloid deriv-
Qing realized a similar transformation using TMSCF3 atives with high molecular complexity, and the start-
as the CF3 source and an external oxidant ing materials are easily accessible.
(Scheme 1b).[10] Meanwhile, Wu, Tu and Glorius inde-
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Copper-Catalyzed Divergent Trifluoromethylation/Cyclization
zation/aromatic substitution pathway. Notably, prod-
uct 3aa is a CF3-incorporated deoxyvasicinone deriva-
tive. Interestingly, addition of a catalytic amount of
pyridine dramatically improved the yield to 57%
(entry 2). This encouraged us to examine different
pyridine-type ligands, and ultimately 2,2’-bipyridine
was found to be superior and furnished the product in
82% yield (entry 3). In contrast, 1,10-phenanthroline
completely shut down the reactivity (entry 4). Further
survey
of
copper
sources
revealed
that
Cu(CH3CN)4PF6, CuI and Cu(OTf)2 were inferior, re-
sulting in significantly lower yields (entries 5–7).
When the reaction was conducted in DMF or CHCl3,
the product was isolated in moderate yields (entries 8
and 9). An attempt to lower the temperature to 608C
gave a decreased yield (entry 10).
With the optimized reaction conditions in hand, we
set out to explore the substrate scope of this transfor-
mation (Table 2). Various unactivated terminal al-
kenes tethered with para-substituted N- acyl cyana-
mides reacted smoothly to furnish the CF3-substituted
4-quinazolinones in synthetically useful yields (3aa–
3hb). A broad range of substituents, such as methyl,
methoxy, cyano, CF3, fluoro, chloro and nitro, were
well tolerated in this process. To our surprise, the
electronic property (rich and deficient) of the aromat-
ic ring did not significantly affect the yields, while di-
substituted terminal alkenes give a slightly higher
yield than the monosubstituted terminal alkenes, lead-
ing to a quaternary carbon center, probably because
the tertiary radical intermediates generated from dis-
ubstituted terminal alkenes were more stable. More-
over, the structure was unambiguously confirmed by
single crystal X-ray analysis of compound 3db.[16] N-
Acyl cyanamides containing an ortho-substituent still
delivered the desired product 3ia in good yield. When
the substituent is placed on the meta position (relative
to acylamide group), the reaction afforded a 2.7:1
mixture of regioisomers (3ja). It is important to note
that heterocyclic moieties like indole, pyrazole and
thiophene, were amenable to this radical cyclization
transformation in moderate to excellent yields (3ka–
3ma). Furthermore, the CF3-incorporated Mackinazo-
Scheme 1. Copper-catalyzed trifluoromethylation of unacti-
vated alkenes.
Recently, Malacria, Lacôte and Fensterbank dis- linone derivatives 3na and 3oa can be accessed from
closed that N-acyl cyanamide could act as a viable the corresponding alkenes in this transformation,
radical acceptor for heterocycles synthesis.[15] Inspired albeit in slightly lower yields. The structure of 3na
by this, we assumed that trifluoromethylation of unac- was confirmed by single crystal X-ray analysis.[17]
tivated alkenes could be combined with N-acyl cyana-
Next, we sought to explore the more challenging
mide. We commenced our study with substrate 1aa unactivated internal alkenes in this protocol. To the
and Togniꢀs reagent 2 in the presence of various best of our knowledge, previous investigations on the
copper sources (Table 1), and 1aa was easily obtained trifluoromethylation of alkenes were mainly con-
by the reaction of an acyl amide containing alkene cerned with terminal alkenes, while internal alkenes
with cyanogen bromide. To our delight, when 1aa was received less attention. When internal alkenes like cy-
treated with Togniꢀs reagent 2 in the presence of clopentene, cyclohexene and cycloheptene (1pa–1xa)
Cu2O at 808C, 4-quinazolinone product 3aa was were investigated in our method, a remarkable spiro-
formed in 25% yield (Table 1, entry 1).This promising 4-quinazolinone can be isolated in moderate to good
result suggested a trifluoromethylation/exo-dig cycli- yields as only one diastereomer (Table 3). The CF3
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Table 1. Optimization of the reaction conditions.[a,b]
Entry
Reaction Conditions
Yield of 3aa [%][b]
1
2
3
4
5
6
7
8
9
10
Cu2O (20 mol%), CH3CN, 808C
Cu2O (20 mol%), pyridine (40 mol%), CH3CN, 808C
25
57
82
0
0
30
0
60
56
20
Cu2O (20 mol%), 2,2’-pyridine (40 mol%), CH3CN, 808C
Cu2O (20 mol%), 1,10-phenanthroline (40 mol%), CH3CN, 808C
Cu(CH3CN)4PF6 (20 mol%), 2,2’-pyridine (20 mol%), CH3CN, 808C
CuI (20 mol%), 2,2’-pyridine (20 mol%), CH3CN, 808C
Cu(OTf)2 (20 mol%), 2,2’-pyridine (20 mol%), CH3CN, 808C
Cu2O (20 mol%), 2,2’-pyridine (40 mol%), CHCl3, 808C
Cu2O (20 mol%), 2,2’-pyridine (40 mol%), DMF, 808C
Cu2O (20 mol%), 2,2’-pyridine (40 mol%), CH3CN, 608C
[a]
Reaction conditions: 1aa (0.2 mmol), 2 (2 equiv.) in 2 mL of solvent under argon for 10 h.
Isolated yields are given.
[b]
group was built as trans isomer in this cyclization, and 6o). The internal alkene was also tolerated well in
the excellent diastereoselectivity should be attributed this process (6p).
to the cyclization process favoring less steric hin-
To gain insight in to the mechanism of these diver-
derance. The structure of 4h was confirmed by single gent trifluoromethylation/cyclization processes of un-
crystal X-ray analysis.[18] Considering the wealth of 4- activated alkenes, control experiments were conduct-
quinazolinones in natural products and pharmaceuti- ed. When radical scavengers such as TEMPO and
cals,[19] this protocol represents a simple, rapid and BHT were added, these transformations delivered the
straightforward entry to these compounds.
desired product only in marginal yields (see the Sup-
When alkenes 5 were subject to the standard condi- porting Information), indicating that a CF3 radical
tion, we found that another trifluoromethylation/aro- might be involved in these cyclizations. Moreover, ki-
matic substitution occurred to furnish dihydroisoqui- netic isotope effects (KIE) were investigated, and the
nolinone 6. This trifluoromethylation/cyclization fash- observed KIEs are only 1.08 and 1.13, suggesting that
À
ion is dramatically different from the aforementioned the C H bond cleavage on the aromatic group is not
transformation, excluding the involvement of a cya- involved in the rate-determining steps [Eq. (1) and
nide group, and is well consistent with Sodeokaꢀs and Eq. (2)].
Nevadoꢀs early findings.[4c,9] The generality was next
examined and is listed in Table 4. Various unactivated
terminal alkenes tethered with para-substituted N-
acyl cyanamides reacted smoothly to furnish the CF3-
containing dihydroisoquinolinones in synthetically
useful yields (6a–6i). A broad range of substituents
was well tolerated in this process. Polysubstituted N-
acyl cyanamides and those containing an ortho-substi-
tutent in the aromatic ring still delivered the desired
product 6j and 6k in moderate yield. The structure of
6g was confirmed by X-ray analysis.[20] When the sub-
stituent is placed on the meta position (relative to the
acylamide group), the reaction afforded a 3:1 mixture
Based on these experiments and previous
of regioisomers (6l). A heterocyclic moiety such as studies,[4b–d,11b,15] a plausible mechanism for this diver-
indole was also applicable in this process to furnish gent trifluoromethylation/cyclization is proposed
product 6m in good yield. Moreover, the disubstituted (Scheme 2). Initially, the Cu(I) precatalyst is first
alkenes were also investigated and were found to be transformed to a highly reactive Cu(II) radical com-
well tolerated in this process to afford the CF3-incor- plex A when treated with Togniꢀs reagent 2. After-
porated products in synthetically useful yields (6n– wards, the CF3 radical is transferred from complex A
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Copper-Catalyzed Divergent Trifluoromethylation/Cyclization
Table 2. Substrate scope of terminal alkenes.[a,b]
Table 3. Substrate scope of internal alkenes.[a,b]
[a]
All the reaction was conducted on a 0.2-mmol scale.
Isolated yields are given.
[b]
Table 4. Trifluoromethylation/cyclization toward dihydroiso-
quinolinones.[a,b]
[a]
All the reaction was conducted on a 0.2 mmol scale.
Isolated yields are given.
[b]
3
À
to the olefin (1 or 5) to form the CF3 C(sp ) bond
and a-alkyl radical B; meanwhile a Cu(II) complex is
released. At this stage, the sequential divergent cycli-
zation occurs. The intermediate B from olefin 1 takes
an exo-dig cyclization route to afford iminyl radical C,
and sequential aromatic substitution of C generates
aryl radical D, which is oxidized by Cu(II) to furnish
the 4-quinazolinones products 3 or 4, with release of
2-iodobenzoic acid and regeneration of Cu(I) to
enable this catalytic cycle. Respecting those species B
generated from 5, this intermediate takes a direct ary-
lation to form E rather than the unfavored 4-exo-dig
[a]
All the reaction was conducted on a 0.2-mmol scale.
Isolated yields are given.
[b]
addition to cyanide, and E is oxidized by Cu(II) to Conclusions
furnish 6, with release of 2-iodobenzoic acid and re-
generation of Cu(I) to enable this catalytic cycle. In summary, a copper-catalyzed divergent trifluoro-
Thus the divergent cyclization in this process is well methylation/cyclization of unactivated alkenes is re-
consistent with Baldwinꢀs rule.
ported. A copper catalyst in the presence of Togniꢀs
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Jing Zheng et al.
Scheme 2. Proposed mechanism for copper-catalyzed divergent trifluoromethylation/cyclization of unactivated alkenes.
1363, 1389, 1207, 1056, 1009, 775, 613 cmÀ1; HR-MS (EI):
reagent is able to trifluoromethylate the unactivated
m/z=282.0983, calcd. for C14H13F3N2O (M+): 282.0980.
alkene, and trigger late-stage cyclization to achieve
molecular complexity for access to CF3-substituted
heterocycles. Moreover, both unactivated terminal
and internal alkenes could be tolerated in this proto-
col. Control experiments and KIE studies were con-
Acknowledgements
ducted to propose a plausible mechanism.
We are greatful for financial support from the National
Nature Science Foundation of China (21202143, 21472163).
References
Experimental Section
[1] a) P. Kirsch, Modern Fluoroorganic Chemistry: Synthe-
sis Reactivity, Applications, 2nd edn., Wiley-VCH, Wein-
heim, 2013; b) M. Shimizu, T. Hiyama, Angew. Chem.
2005, 117, 218; Angew. Chem. Int. Ed. 2005, 44, 214;
c) M. Schlosser, Angew. Chem. 2006, 118, 5558; Angew.
Chem. Int. Ed. 2006, 45, 5432; d) K. Müller, C. Faeh, F.
Diederich, Science 2007, 317, 1881; e) S. Purser, P. R.
Moore, S. Swallow, V. Gouverneur, Chem. Soc. Rev.
2008, 37, 320; f) W. K. Hagmann, J. Med. Chem. 2008,
51, 4359; g) S. K. Ritter, Chem. Eng. News 2012, 90, 10.
[2] For reviews, see: a) J.-A. Ma, D. Cahard, Chem. Rev.
2004, 104, 6119; b) T. Furuya, A. S. Kamlet, T. Ritter,
Nature 2011, 473, 470; c) O. A. Tomashenko, V. V.
Grushin, Chem. Rev. 2011, 111, 4475; d) E. Merino, C.
Nevado, Chem. Soc. Rev. 2014, 43, 6598; e) X. Liu, C.
Xu, M. Wang, Q. Liu, Chem. Rev. 2015, 115, 683; f) X.-
H. Xu, K. Matsuzaki, N. Shibata, Chem. Rev. 2015, 115,
731; g) J. Charpentier, N. Früh, A. Togni, Chem. Rev.
2015, 115, 650; h) X. Yang, T. Wu, R. J. Phipps, F. D.
Toste, Chem. Rev. 2015, 115, 825; i) C. Alonso, E. M.
Marigorta, G. Rubiales, F. Palacios, Chem. Rev. 2015,
115, 1847.
Typical Procedure for Synthesis of 3aa
A
Schlenk tube containing copper(I) oxide (5.8 mg,
20 mol%), 2,2’-bipyridine (11.2 mg, 40 mol%), and Togniꢀs
reagent 2 (126 mg, 0.4 mmol) was evacuated and purged
with argon three times. Afterwards, a CH3CN (2 mL) solu-
tion of N-cyano-N-(3-methylbut-3-en-1-yl)benzamide 1aa
(43 mg, 0.2 mmol) was added via syringe. The solution was
kept at 808C for 10 h. Then the solution was diluted with
CH2Cl2 and transferred to a round-bottom flask. Silica was
added to the flask and volatiles were evaporated under
vacuum. The purification was performed by flash column
chromatography on silica gel using ethyl acetate/petroleum
ether (v/v, 1:5) as eluent to give 3aa as a pale yellow solid;
yield: 46 mg (82%); mp 91–928C; 1H NMR (CDCl3,
400 MHz): d=8.29 (dd, J1 =8.0 Hz, J2 =1.2 Hz, 1H), 7.76–
7.72 (m, 1H), 7.67 (dd, J1 =8.4 Hz, J2 =0.8 Hz, 1H), 7.46
(dq, J1 =7.4 Hz, J2 =1.2 Hz, 1H), 4.30 (dq, J1 =11.2 Hz, J2 =
3.0 Hz, 1H), 4.03 (dq, J1 =12.4 Hz, J2 =1.6 Hz, 1H), 2.93
(dq, J1 =15.2 Hz, J2 =11.2 Hz, 1H), 2.55 (dq, J1 =15.2 Hz,
J2 =11.6 Hz, 1H), 2.43–2.35 (m, 1H), 2.30–2.24 (m, 1H),
1.48 (s, 3H); 13C NMR (CDCl3, 100 MHz), d: 162.56, 161.05,
149.33, 134.37, 126.60 (q, J=276.0 Hz), 127.35, 126.70,
126.58, 121.01, 44.04 (q, J=2.0 Hz), 43.51, 41.56 (q, J=
27.0 Hz), 32.95, 24.04; 19F NMR (CDCl3, 470 MHz), d:
À60.29; IR (KBr): v=2989, 2947, 2905, 1660, 1614, 1437,
[3] For selected work, see: a) J. Joubert, S. Roussel, C.
Christophe, T. Billard, B. R. Langlois, T. Vidal, Angew.
Chem. 2003, 115, 3241; Angew. Chem. Int. Ed. 2003, 42,
3133; b) V. V. Grushin, W. J. Marshall, J. Am. Chem.
750
asc.wiley-vch.de
ꢁ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2016, 358, 746 – 751

FULL PAPERS
Copper-Catalyzed Divergent Trifluoromethylation/Cyclization
Soc. 2006, 128, 12644; c) N. D. Ball, J. W. Kampf, M. S.
Sanford, J. Am. Chem. Soc. 2010, 132, 2878; d) X.
Wang, L. Truesdale, J.-Q. Yu, J. Am. Chem. Soc. 2010,
132, 3648; e) D. A. Nagib, D. W. C. MacMillan, Nature
2011, 480, 224; f) Y. Ji, T. Brueckl, R. D. Baxter, Y. Fu-
jiwara, I. B. Seiple, S. Su, D. G. Blackmond, P. S. Baran,
Proc. Natl. Acad. Sci. USA 2011, 108, 14411; g) C.
Huang, T. Liang, S. Harada, E. Lee, T. Ritter, J. Am.
Chem. Soc. 2011, 133, 13308; h) Y. Nomura, E. Tokuna-
ga, N. Shibata, Angew. Chem. 2011, 123, 1925; Angew.
Chem. Int. Ed. 2011, 50, 1885; i) H. Morimoto, T. Tsu-
bogo, N. D. Litvinas, J. F. Hartwig, Angew. Chem. 2011,
123, 3877; Angew. Chem. Int. Ed. 2011, 50, 3793; j) Y.
Yasu, T. Koike, M. Akita, Angew. Chem. 2012, 124,
9705; Angew. Chem. Int. Ed. 2012, 51, 9567; k) Y.
Zeng, L. Zhang, Y. Zhao, C. Ni, J. Zhao, J. Hu, J. Am.
Chem. Soc. 2013, 135, 2955; l) J.-J. Dai, C. Fang, B.
Xiao, J. Yi, J. Xu, Z.-J. Liu, X. Lu, L. Liu, Y. Fu, J. Am.
Chem. Soc. 2013, 135, 8436.
Sahoo, J.-L. Li, F. Glorius, Angew. Chem. 2015, 127,
4878; Angew. Chem. Int. Ed. 2015, 54, 5796.
[12] a) P. Yu, J.-S. Lin, L. Li, S.-C. Zheng, Y.-P. Xiong, L.-J.
Zhao, B. Tan, X.-Y. Liu, Angew. Chem. 2014, 126,
12084; Angew. Chem. Int. Ed. 2014, 53, 11890; b) P. Yu,
S.-C. Zheng, N.-Y. Yang, B. Tan, X.-Y. Liu, Angew.
Chem. 2015, 127, 4113; Angew. Chem. Int. Ed. 2015, 54,
4041.
[13] K. Matcha, A. P. Antonchick, Angew. Chem. 2014, 126,
12154; Angew. Chem. Int. Ed. 2014, 53, 11960.
[14] a) S. Cui, Y. Zhang, Q. Wu, Chem. Sci. 2013, 4, 3421;
b) S. Cui, Y. Zhang, D. Wang, Q. Wu, Chem. Sci. 2013,
4, 3912; c) Y. Zhang, Q. Wu, S. Cui, Chem. Sci. 2014, 5,
297; d) Q. Wu, Y. Zhang, S. Cui, Org. Lett. 2014, 16,
1350; e) J. Zheng, Y. Zhang, S. Cui, Org. Lett. 2014, 16,
3560; f) Y. Zhang, J. Zheng, S. Cui, J. Org. Chem. 2014,
79, 6490; g) Y. Zhang, M. Shen, S. Cui, T. Hou, Bioorg.
Med. Chem. Lett. 2014, 24, 5470; h) Y. Zhang, D.
Wang, S. Cui, Org. Lett. 2015, 17, 2494.
[4] a) X. Mu, T. Wu, H.-Y. Wang, Y.-L. Guo, G. Liu, J.
Am. Chem. Soc. 2012, 134, 878; b) W. Kong, M. Casi-
miro, E. Merino, C. Nevado, J. Am. Chem. Soc. 2013,
135, 14480; c) W. Kong, M. Casimiro, N. Fuentes, E.
Merino, C. Nevado, Angew. Chem. 2013, 125, 13324;
Angew. Chem. Int. Ed. 2013, 52, 13086; d) N. Fuentes,
W. Kong, L. Fernµndez-Sµnchez, E. Merino, C.
Nevado, J. Am. Chem. Soc. 2015, 137, 964.
[5] a) A. T. Parsons, S. L. Buchwald, Angew. Chem. 2011,
123, 9286; Angew. Chem. Int. Ed. 2011, 50, 9120; b) R.
Zhu, S. L. Buchwald, J. Am. Chem. Soc. 2012, 134,
12462; c) R. Zhu, S. L. Buchwald, Angew. Chem. 2013,
125, 12887; Angew. Chem. Int. Ed. 2013, 52, 12655.
[6] X. Wang, Y. Ye, S. Zhang, J. Feng, Y. Xu, Y. Zhang, J.
Wang, J. Am. Chem. Soc. 2011, 133, 16410.
[7] J. Xu, Y. Fu, D.-F. Luo, Y.-Y. Jiang, B. Xiao, Z.-J. Liu,
T.-J. Gong, L. Liu, J. Am. Chem. Soc. 2011, 133, 15300.
[8] a) F. Wang, D. Wang, X. Mu, P. Chen, G. Liu, J. Am.
Chem. Soc. 2014, 136, 10202; b) F. Wang, X. Qi, Z.
Liang, P. Chen, G. Liu, Angew. Chem. 2014, 126, 1912;
Angew. Chem. Int. Ed. 2014, 53, 1881.
[9] a) H. Egami, R. Shimizu, S. Kawamura, M. Sodeoka,
Angew. Chem. 2013, 125, 4092; Angew. Chem. Int. Ed.
2013, 52, 4000; b) S. Kawamura, H. Egami, M. Sode-
oka, J. Am. Chem. Soc. 2015, 137, 4865; c) H. Egami,
R. Shimizu, M. Sodeoka, J. Fluorine Chem. 2013, 152,
51.
[15] a) A. Servais, M. Azzouz, D. Lopes, C. Courillon, M.
Malacria, Angew. Chem. 2007, 119, 582; Angew. Chem.
Int. Ed. 2007, 46, 576; b) M.-H. Larraufie, C. Ollivier,
L. Fensterbank, M. Malacria, E. Lacôte, Angew. Chem.
2010, 122, 2224; Angew. Chem. Int. Ed. 2010, 49, 2178;
c) M.-H. Larraufie, C. Courillon, C. Ollivier, E. Lacôte,
M. Malacria, L. Fensterbank, J. Am. Chem. Soc. 2010,
132, 4381.
[16] CCDC 1059895 contains the supplementary crystallo-
graphic data for this paper. These data can be obtained
free of charge from The Cambridge Crystallographic
Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
[17] CCDC 1401298 contains the supplementary crystallo-
graphic data for this paper. These data can be obtained
free of charge from The Cambridge Crystallographic
Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
[18] CCDC 1421628 contains the supplementary crystallo-
graphic data for this paper. These data can be obtained
free of charge from The Cambridge Crystallographic
Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
[19] a) J. P. Michael, Nat. Prod. Rep. 2004, 21, 650; b) C.-W.
Yu, P.-T. Chang, L.-W. Hsin, J.-W. Chern, J. Med.
Chem. 2013, 56, 6775; c) F. H. Darras, S. Wehle, G.
Huang, C. A. Sotriffer, M. Decker, Bioorg. Med. Chem.
2014, 22, 4867; d) R. Bouley, M. Kummarasiri, Z. Peng,
L. H. Otero, W. Song, M. A. Suckow, V. A. Schroeder,
W. R. Wolter, E. Lastochkin, N. T. Antunes, H. Pi, S.
Vakulenko, J. A. Hermoso, M. Chang, S. Mobashery, J.
Am. Chem. Soc. 2015, 137, 1738.
[10] X.-Y. Jiang, F.-L. Qing, Angew. Chem. 2013, 125,
14427; Angew. Chem. Int. Ed. 2013, 52, 14177.
[11] a) X. Liu, F. Xiong, X. Huang, L. Xu, P. Li, X. Wu,
Angew. Chem. 2013, 125, 7100; Angew. Chem. Int. Ed.
2013, 52, 6962; b) Z.-M. Chen, W. Bai, S.-H. Wang, B.-
M. Yang, Y.-Q. Tu, F.-M. Zhang, Angew. Chem. 2013,
125, 9963; Angew. Chem. Int. Ed. 2013, 52, 9781; c) B.
[20] CCDC 1404843 contains the supplementary crystallo-
graphic data for this paper. These data can be obtained
free of charge from The Cambridge Crystallographic
Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
Adv. Synth. Catal. 2016, 358, 746 – 751
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