Photoinduced, Copper-Promoted Regio- and Stereoselective Decarboxylative Alkylation of α,β-Unsaturated Acids with Alkyl Iodides

Article abstract of DOI:10.1021/acs.orglett.7b03289

The first example of UV light-induced, copper-catalyzed regio- and stereoselective decarboxylative coupling of α,β-unsaturated acids with alkyl iodides was reported. Under standard conditions, the 1°, 2°, and 3° alkyl iodides proceeded smoothly with the E-selective alkenes obtained in uniformly good yields and high stereoselectivities.

Full text of DOI:10.1021/acs.orglett.7b03289

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX-XXX
Photoinduced, Copper-Promoted Regio- and Stereoselective
Decarboxylative Alkylation of α,β-Unsaturated Acids with Alkyl
Iodides
Chao Wang,† Yingjie Lei,† Mengzhun Guo, Qinyu Shang, Hong Liu, Zhaoqing Xu,* and Rui Wang*
Key Laboratory of Preclinical Study for New Drugs of Gansu Province, The Institute of Pharmacology, School of Basic Medical
Science, Lanzhou University, 199 West Donggang Road, Lanzhou 730000, China
S
* Supporting Information
ABSTRACT: The first example of UV light-induced, copper-
catalyzed regio- and stereoselective decarboxylative coupling of
α,β-unsaturated acids with alkyl iodides was reported. Under
standard conditions, the 1°, 2°, and 3° alkyl iodides proceeded
smoothly with the E-selective alkenes obtained in uniformly
good yields and high stereoselectivities.
Scheme 1. Decarboxylative Alkylation of α,β-Unsaturated
Acids
lkyl-substituted alkenes are important structural motifs that
frequently appear in chemicals, materials, natural products,
A
and pharmaceuticals.1 In this context, preparation of alkylated
alkenes is among the most important parts in organic synthetic
chemistry. The Pd-catalyzed cross couplings between alkenyl
halides and alkylmetal reagents provide direct ways to synthesize
alkyl-substituted alkenes.2 However, the sterically specific alkenyl
halides are normally expensive and not easily obtained. In the
meantime, alkylmetal reagents suffer from instability and lack of
functional group compatibility, and the preparation procedures
from alkyl halides always require relatively restricted conditions.
Alkyl halides are commercially available or readily accessible, and
another benefit is their structural diversity and functional group
tolerance. It is ideal to directly use alkyl halides as the coupling
partner for alkene alkylation reactions instead of alkylmetal
reagents. Unfortunately, the couplings of alkyl halides with
olefins are normally problematic, due to the decreased rates of
oxidative addition using sp3-hybridized electrophiles3 and the
predisposition of putative alkyl palladium species to undergo
dehydrohalogenation.4 In the past few years, transition-metal-
catalyzed Heck-type radical alkylation reactions provided
alternative routes to realize the alkylation of alkenes by directly
using alkyl halides. However, limitations such as high temper-
ature and long reaction time, low to moderate stereoselectivities,
limited substrate scopes (α-carbonyl alkyl halides or benzyl
halides), or using of stoichiometric amount of Grignard reagent
as activators still exist.5
reported a novel Ru-catalyzed, visible light-induced chemo- and
regioselective decarboxylative alkylation of α,β-unsaturated acids
by using stoichiometric amount of hypervalent iodine as the
mediator. This protocol required the preparation of alkyl
trifluoroborate reagents which are still difficult in most cases.8a
Additionally, Duan8b and Wang8c recently successively reported
the coupling of aryl carboxylic acids with redox-active ester of
alkyl carboxylic acid induced by visible light. Wang8d and Wu8e
described copper-catalyzed decarboxylative trifluoroethylation of
cinnamic acids. However, in view of atom- and step-economy,
the direct use of alkyl halides as the highly regio- and
chemoselective alkylation reagents for decarboxylative alkylation
of α,β-unsaturated acids in a catalytic manner is highly desirable
but yet not realized.
α,β-Unsaturated acids are stable and readily available in high
stereoselectivities, which were successfully applied in decarbox-
ylative cross couplings for the construction of C(sp2)−C(sp2)
bonds.6 Recently, transition-metal-catalyzed alkyl radical addi-
tion−elimination processes of α,β-unsaturated acids were
developed. Using this strategy, highly stereoselective alkylation
of alkenes could be realized. However, the oxidative conditions
and high temperature lead to narrow substrate scopes or poor
regioselectivities of the alkyl groups, which restrict its synthetic
applications (Scheme 1).7 Very recently, Chen and co-workers
In the past few years, Ir- and Ru-catalyzed photoredox were
reported to form alkyl radicals from alkyl halides in the present of
reductants and widely applied in alkyl radical coupling reactions.9
In contrast, Cu has been used scarcely as photoredox catalysts for
organic transformations,10 although early work by the groups of
Received: October 22, 2017
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.7b03289
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Kutal and Mitani described it.11 Recently, the using of ultraviolet
(UV) light as an efficient energy source in organic synthesis has
received more and more attention.12 Very recently, Fu, Peters,
and Ackermann reported the copper salt catalyzed radical
couplings of organic halides with amide, cyano, and heterocycles
under UV light promotion.13 In the reactions, the excited state of
CuI was oxidatively quenched by organic halides and formed the
R•. Inspired by these precedents, we envisioned that under UV
light irradiation, by using a suitable single electron reductant,
alkyl halide could also be converted to alkyl radical through the
Cu-catalyzed oxidative quenching cycle without the assistance of
expensive Ru or Ir photocatalysts. Herein, we report the first
example of copper-promoted decarboxylative alkylations of α,β-
unsaturated carboxylic acids with 100 W UVC compact
fluorescent light bulb irradiation under mild conditions.14 The
direct using of readily alkyl iodides as alkylation reagents avoids
the preparation of alkylmetals. Furthermore, the 1°, 2°, and 3°
alkyl iodides proceeded smoothly, and the E selective alkenes
were obtained in uniformly good yields with high chemo- and
regioselectivities. Moreover, the absence of oxidants and strong
inorganic bases provided good functional group tolerance.
Our investigation was initiated by using 4-fluorocinnamic acid
and cyclohexyl iodide as model substrates and irradiation with
100 W UVC compact fluorescent light bulbs under room
temperature. DIPEA was reported as a single-electron-transfer
agent for reducing CuII to CuI in photoinduced oxidative
quenching cycles.15 We assumed that DIPEA might also suitable
for our purpose (Table 1, entry 1; see the Supporting
Information for details). When the reaction mixture was
irradiated with longer wavelength light (365 nm), little coupling
product was observed. Reducing the light bulbs to 50 W led to a
low conversion. The control experiments indicated that UV
irradiation and DIPEA were essential for this transformation
(entries 2 and 3). Although cupric acetylacetonate (Cu(acac)2)
was unnecessary, the yield of desired product was more sharply
decreased than under standard conditions (entry 4). Other
copper salts could not promote this approach efficiently (entries
5). Replacing DIPEA with other tertiary amines, secondary
amines, or inorganic bases led to significantly lower yields
(entries 6 and 7). Solvents screening indicated that acetone was
the best choice (entry 8). It should be noted that when
cyclohexyl bromide was tested under the established conditions,
the yield of cyclohexyl-substituted alkene was 58% (entry 9).
Reducing the amount of Cu(acac)2 resulted in substantial drop of
yields (entries 10 and 11). Furthermore, decreasing the loading
of cyclohexyl iodide or DIPEA resulted negative effects on
reaction yields, respectively (entries 12 and 13). The reaction was
sensitive to oxygen (entry 14). Further improving the yield by
extending the reaction time to 5 h was not effective, whereas a
small decrease of E/Z ratio was noticed, which might be caused
by the strong absorption of alkene product at 254 nm (entry 15,
see the Supporting Information).16,17 Finally, under optimal
conditions, the decarboxylative alkylation product 3a was
obtained in 81% isolated yield with E/Z > 20:1 (entry 1).
With the optimized conditions in hand, we examined the scope
of α,β-unsaturated carboxylic acids. As shown in Scheme 2, aryl
Scheme 2. Scope of Various α,β-unsaturated Carboxylic and
a
Alkyl Iodides
a
Table 1. Optimization of Reaction Conditions
b
entry
change from the “standard conditions”
yield (%)
1
no change
84 (81)
0
2
no hv
3
no i-Pr2NEt
0
4
no Cu(acac)2
35
5
other copper salts instead of Cu(acac)2
other amines instead of i-Pr2NEt
inorganic bases instead of i-Pr2NEt
other solvents instead of acetone
CyBr instead of CyI
10 mol % of Cu(acac)2
5 mol % of Cu(acac)2
3.0 equiv of CyI
18−52
0−74
0
6
7
8
0−75
58
9
10
11
12
13
14
64
47
70
3.0 equiv of i-Pr2NEt
Under O2 atmosphere
5 h
72
36
c
15
84
a
Standard conditions were carried out by using 4-fluorocinnamic acid
(0.1 mmol), cyclohexyl iodide (5.0 equiv), Cu(acac)2 (20 mol %), i-
a
Pr2NEt (4.0 equiv), under Ar, and stirred at room temperature for 2 h
Reaction conditions: vinyl carboxylic acid 1 (0.2 mmol), alkyl iodide
b
under UV light irradiation. Yield was determined by 19F NMR using
2 (1.0 mmol), Cu(acac)2 (0.04 mmol), i-Pr2NEt (0.8 mmol), under
b
benzotrifluoride as an internal standard, and the number in
parentheses refers isolated yield. E/Z = 15:1.
Ar, and stirred at room temperature for 2 h under 100 W UVC. E/Z
ratio was determined by analysis of H NMR.
c
1
B
DOI: 10.1021/acs.orglett.7b03289
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
vinyl carboxylic acids with various substituted groups including
electron-withdrawing and electron-donating groups at the p-, m-,
or o-position provided good to excellent yields (3aa−ma, 68−
86%) with high stereoselectivities (E/Z > 20:1). Bracingly,
heteroaromatic α,β-unsaturated carboxylic acid also reacted
smoothly under the standard conditions and gave desired
product 3na in 65% yield. We next studied the generality of alkyl
iodides with different structures. The primary, secondary, and
tertiary iodides were all tolerant, whereas in cases of using
primary alkyl iodides, a small decrease of E/Z ratio was noted
(3kb−ee, E/Z ≥ 11:1). It should be noted that alkyl iodides
bearing sensitive functional groups such as ether, triple bonds,
and N-Boc groups all proceeded well under the standard
conditions with good yields (3kb−nh, 55−75%). Moreover, the
reactions of halogen-substituted aromatic vinyl carboxylic acids
efficiently proceeded to form the corresponding alkylated
alkenes in good yields, with the halogen substituents untouched
during the reaction, which render the coupling products good
candidates for further transformations such as transition-metal-
catalyzed functionalization of the C−halogen bonds (3ca, see the
SI for details). The sterically demanding 1-adamantyl iodide 2i
was efficiently reacted and the yields were up to 76% (3gi and
3ei). Acyl-substituted vinyl carboxylic acid 1r and the conjugated
diene substrate 1s gave the corresponding products 3ri and 3si in
moderate yields, respectively. We were pleased to find that under
the stated conditions perfluorobutyl iodide smoothly reacted to
furnish the perfluorobutyl-substituted alkene 3ej in good yield
and high stereoselectivity.
Scheme 4. Mechanistic Studies
Scheme 5. Proposed Mechanism
generation of CuI and an amine radical cation.15 Under UV light
irradiation, CuI was excited to its triplet state [CuI]*, which
engages in an electron-transfer reaction with alkyl iodide to
furnish alkyl radical and I− along with recycling of CuII.13a,d On
the other hand, the carboxylate anion A was formed from α,β-
unsaturated acids under basic conditions. A radical addition of
alkyl radical R• to A took place and gave the radical intermediate
B.18 The loss of carbon dioxide results in intermediate C, which
was oxidized by amine radical cation, and alkyl-substituted alkene
3 was obtained.19,20
To demonstrate the synthetic utility of this methodology, this
catalytic system was applied to the decarboxylative alkylation and
perfluoroalkylation of estrone derivative 1t (Scheme 3). The
Scheme 3. Alkylation and Perfluoroalkylation of Estrone
Derivative 1t
In summary, we describe a novel copper-promoted decarbox-
ylative coupling of α,β-unsaturated acids with alkyl iodides under
UV light irradiation. This strategy could efficiently construct 1°,
2°, and 3° alkyl-substituted alkenes containing various sensitive
groups on both aromatic rings of α,β-unsaturated acids and alkyl
iodides. The coupling reactions were found to be stereoselective,
with the trans-alkenes (E/Z from 11:1 to >20:1) formed in good
to excellent yields. Moreover, the acyl-substituted vinyl
carboxylic acid, the conjugated diene substrate carboxylic acid,
as well as perfluorobutyl iodide also proceeded well under
standard conditions.
reactions afforded corresponding products 3ti and 3tj in 72% and
67% yields with high stereoselectivities (E/Z > 20:1),
respectively. These excellent performances illustrated the
potential application values of our methodology in drug
discovery and synthesis of natural products.
To gain some mechanistic insight into this decarboxylative
coupling, a radical-trapping experiment was carried out (Scheme
4). When radical scavenger TEMPO was added to the standard
reaction, the reaction was completely shut down. In the
meanwhile, the radical trapping product 7 was isolated in 45%
yield, which indicated the formation of alkyl radical. To explore
the influence of bases, all types of inorganic bases were used
instead of DIPEA. The negative results demonstrated the
importance of organic amines in this UV-promoted decarbox-
ylative coupling process.
ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.orglett.7b03289.
Experimental procedures and full analytical data (PDF)
AUTHOR INFORMATION
Corresponding Authors
■
*E-mail: zqxu@lzu.edu.cn.
*E-mail: wangrui@lzu.edu.cn.
ORCID
Zhaoqing Xu: 0000-0001-7663-6249
Rui Wang: 0000-0002-4719-9921
Author Contributions
†C.W. and Y.L. contributed equally.
Although multiple scenarios can be envisaged, on the basis of
the above investigations and previous reports,10 a possible
mechanism was proposed in Scheme 5. As a single electron-
transfer agent, DIPEA could reduce CuII with concomitant
C
DOI: 10.1021/acs.orglett.7b03289
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
(10) For reviews, see: (a) Paria, S.; Reiser, O. ChemCatChem 2014, 6,
2477. (b) Reiser, O. Acc. Chem. Res. 2016, 49, 1990. (c) Hernandez-
Perez, A. C.; Collins, S. K. Acc. Chem. Res. 2016, 49, 1557.
Notes
The authors declare no competing financial interest.
(11) (a) Grutsch, P. A.; Kutal, C. J. Am. Chem. Soc. 1979, 101, 4228.
(b) Mitani, M.; Kato, I.; Koyama, K. J. Am. Chem. Soc. 1983, 105, 6719.
(12) Some recent examples of UV-promoted reactions: (a) Liu, W.; Li,
L.; Li, C.-J. Nat. Commun. 2015, 6, 6526. (b) Li, L.; Liu, W.; Zeng, H.;
Mu, X.; Cosa, G.; Mi, Z.; Li, C.-J. J. Am. Chem. Soc. 2015, 137, 8328.
(c) Li, L.; Mu, X.; Liu, W.; Wang, Y.; Mi, Z.; Li, C.-J. J. Am. Chem. Soc.
2016, 138, 5809. (d) Liu, W.; Chen, Z.; Li, L.; Wang, H.; Li, C.-J. Chem. -
Eur. J. 2016, 22, 5888. (e) Yang, X.; Liu, W.; Li, L.; Wei, W.; Li, C.-J.
Chem. - Eur. J. 2016, 22, 15252. (f) Mfuh, A. M.; Doyle, J. D.; Chhetri, B.;
Arman, H. D.; Larionov, O. V. J. Am. Chem. Soc. 2016, 138, 2985.
(g) Mfuh, A. M.; Nguyen, V. T.; Chhetri, B.; Burch, J. E.; Doyle, J. D.;
Nesterov, V. N.; Arman, H. D.; Larionov, O. V. J. Am. Chem. Soc. 2016,
138, 8408. (h) Seo, H.; Katcher, M. H.; Jamison, T. F. Nat. Chem. 2016,
9, 453. (i) Xie, J.; Zhang, T.; Chen, F.; Mehrkens, N.; Rominger, F.;
Rudolph, M.; Hashmi, A. S. K. Angew. Chem., Int. Ed. 2016, 55, 2934.
(j) Xie, J.; Li, J.; Wurm, T.; Weingand, V.; Sung, H.-L.; Rominger, F.;
Rudolph, M.; Hashmi, A. S. K. Org. Chem. Front. 2016, 3, 841.
ACKNOWLEDGMENTS
■
We are grateful for the grants from the NSFC (No. 21432003)
and the Fundamental Research Funds for the Central
Universities (lzu-jbky-2016-216).
REFERENCES
■
(1) Preparation of Alkenes: A Practical Approach; Williams, J. M. J.;
Oxford University Press: Oxford, UK, 1996.
(2) Jana, R.; Pathak, T. P.; Sigman, M. S. Chem. Rev. 2011, 111, 1417.
(3) The Chemistry of the Metal−Carbon Bond; Patai, S., Stille, J. K., Eds.;
Wiley Online Library: New York, 1985; Vol. 2, Chapter 9.
(4) Bissember, A. C.; Levina, A.; Fu, G. C. J. Am. Chem. Soc. 2012, 134,
14232.
(5) (a) McMahon, C. M.; Alexanian, E. J. Angew. Chem., Int. Ed. 2014,
53, 5974. (b) Zou, Y.; Zhou, J. Chem. Commun. 2014, 50, 3725. (c) Zhu,
N.; Zhao, J.; Bao, H. Chem. Sci. 2017, 8, 2081. (d) Liu, C.; Tang, S.; Liu,
D.; Yuan, J.; Zheng, L.; Meng, L.; Lei, A. Angew. Chem., Int. Ed. 2012, 51,
3638. (e) Liu, Q.; Yi, H.; Liu, J.; Yang, Y.; Zhang, X.; Zeng, Z.; Lei, A.
Chem. - Eur. J. 2013, 19, 5120. (f) Zhang, X.; Yi, H.; Liao, Z.; Zhang, G.;
Fan, C.; Qin, C.; Liu, J.; Lei, A. Org. Biomol. Chem. 2014, 12, 6790.
(g) Ikeda, Y.; Nakamura, T.; Yorimitsu, H.; Oshima, K. J. Am. Chem. Soc.
2002, 124, 6514. (h) Affo, W.; Ohmiya, H.; Fujioka, T.; Ikeda, Y.;
Nakamura, T.; Yorimitsu, H.; Oshima, K.; Imamura, Y.; Mizuta, T.;
Miyoshi, K. J. Am. Chem. Soc. 2006, 128, 8068. (i) Matsubara, R.;
Gutierrez, A. C.; Jamison, T. F. J. Am. Chem. Soc. 2011, 133, 19020.
(j) Nishikata, T.; Noda, Y.; Fujimoto, R.; Sakashita, T. J. Am. Chem. Soc.
2013, 135, 16372. (k) Shukla, P.; Hsu, Y.-C.; Cheng, C.-H. J. Org. Chem.
2006, 71, 655. (l) Xie, J.; Li, J.; Weingand, V.; Rudolph, M.; Hashmi, A.
S. K. Chem. - Eur. J. 2016, 22, 12646. (m) Branchaud, B. P.; Detlefsen, W.
D. Tetrahedron Lett. 1991, 32, 6273. (n) Lebedev, S. A.; Lopatina, V. S.;
Petrov, E. S.; Beletskaya, I. P. J. Organomet. Chem. 1988, 344, 253.
(o) Terao, J.; Watabe, H.; Miyamoto, M.; Kambe, N. Bull. Chem. Soc.
(13) (a) Ratani, T. S.; Bachman, S.; Fu, G. C.; Peters, J. C. J. Am. Chem.
Soc. 2015, 137, 13902. (b) Uyeda, C.; Tan, Y.; Fu, G. C.; Peters, J. C. J.
Am. Chem. Soc. 2013, 135, 9548. (c) Ziegler, D. T.; Choi, J.; Munoz-
̃
Molina, J. M.; Bissember, A. C.; Peters, J. C.; Fu, G. C. J. Am. Chem. Soc.
2013, 135, 13107. (d) Do, H.-Q.; Bachman, S.; Bissember, A. C.; Peters,
J. C.; Fu, G. C. J. Am. Chem. Soc. 2014, 136, 2162. (e) Yang, F.; Koeller,
J.; Ackermann, L. Angew. Chem., Int. Ed. 2016, 55, 4759.
(14) Four 25 W UVC bulbs were used, which can be purchased from
the supermarket ($∼9 each).
(15) (a) Baralle, A.; Fensterbank, L.; Goddard, J.-P.; Ollivier, C. Chem. -
Eur. J. 2013, 19, 10809. (b) Michelet, B.; Deldaele, C.; Kajouj, S.;
Moucheron, C.; Evano, G. Org. Lett. 2017, 19, 3576.
(16) UV-promoted Heck-type radical coupling of styrenes and alkyl
iodides in low stereoselectivities (Z/E = 1:1−2.9:1) under strong base
conditions (10.8 equiv of NaOtBu) and using a highly excess amount of
alkyl halides (10 equiv): Liu, W.; Li, L.; Chen, Z.; Li, C.-J. Org. Biomol.
Chem. 2015, 13, 6170.
(17) An excess amount of cyclohexyl iodide was necessary for a rapid
conversion, and the residue was collected after the reaction without
significant side reactions.
(18) Xu, Y.; Tang, X.; Hu, W.; Wu, W.; Jiang, H. Green Chem. 2014, 16,
3720.
(19) Although the tertiary amine functions as a catalyst, a
stoichiometric amount of DIPEA was required for good conversions.
The requirement for a high concentration of amine may be a reflection
of its dual roles as an electron-transfer agent and a base. For other
examples using stoichiometric amount of tertiary amines as electron-
transfer agents in photoredox reactions, see ref 15 and: (a) Jeffrey, J. L.;
Jpn. 2003, 76, 2209. (p) Brase, S.; Waegell, B.; de Meijere, A. Synthesis
̈
1998, 1998, 148.
(6) (a) Goossen, L. J.; Rodríguez, N.; Melzer, B.; Linder, C.; Deng, G.;
Levy, M. J. Am. Chem. Soc. 2007, 129, 4824. (b) Wang, Z.; Ding, Q.; He,
X.; Wu, J. Org. Biomol. Chem. 2009, 7, 863. (c) Yamashita, M.; Hirano,
K.; Satoh, T.; Miura, M. Chem. Lett. 2010, 39, 68. (d) Yang, Y.; Chen, L.;
Zhang, Z.; Zhang, Y. Org. Lett. 2011, 13, 1342. (e) Jin, Y.; Fu, H. Asian J.
Org. Chem. 2017, 6, 368.
(7) (a) Rong, G.; Liu, D.; Lu, L.; Yan, H.; Zheng, Y.; Chen, J.; Mao, J.
Tetrahedron 2014, 70, 5033. (b) Yang, H.; Yan, H.; Sun, P.; Zhu, Y.; Lu,
L.; Liu, D.; Rong, G.; Mao, J. Green Chem. 2013, 15, 976. (c) Wang, C.-
Y.; Song, R.-J.; Wei, W.-T.; Fan, J.-H.; Li, J.-H. Chem. Commun. 2015, 51,
2361. (d) Zhao, J.; Fang, H.; Han, J.; Pan, Y. Beilstein J. Org. Chem. 2013,
9, 1718. (e) Yang, H.; Sun, P.; Zhu, Y.; Yan, H.; Lu, L.; Qu, X.; Li, T.;
Mao, J. Chem. Commun. 2012, 48, 7847. (f) Cui, Z.; Shang, X.; Shao, X.-
F.; Liu, Z.-Q. Chem. Sci. 2012, 3, 2853. (g) Mai, W.-P.; Song, G.; Sun, G.-
C.; Yang, L.-R.; Yuan, J.-W.; Xiao, Y.-M.; Mao, P.; Qu, L.-B. RSC Adv.
2013, 3, 19264. (h) Ji, J.; Liu, P.; Sun, P. Chem. Commun. 2015, 51, 7546.
(i) Zhang, J.-X.; Wang, Y.-J.; Wang, N.-X.; Zhang, W.; Bai, C.-B.; Li, Y.-
H.; Wen, J.-L. Synlett 2014, 25, 1621. (j) Zhang, J.-X.; Wang, Y.-J.;
Zhang, W.; Wang, N.-X.; Bai, C.-B.; Xing, Y.-L.; Li, Y.-H.; Wen, J.-L. Sci.
Rep. 2015, 4, 7446. (k) Zhao, J.; Zhou, W.; Han, J.; Li, G.; Pan, Y.
Tetrahedron Lett. 2013, 54, 6507. (l) Liu, Z.; Wang, L.; Liu, D.; Wang, Z.
Synlett 2015, 26, 2849.
Petronijevic,
8404. (b) Petronijevic,
Chem. Soc. 2013, 135, 18323. (c) Amador, A. G.; Sherbrook, E. M.;
Yoon, T. P. J. Am. Chem. Soc. 2016, 138, 4722.
́
F. R.; MacMillan, D. W. C. J. Am. Chem. Soc. 2015, 137,
́
F. R.; Nappi, M.; MacMillan, D. W. C. J. Am.
(20) In the process of conditional optimization, 35% of 3aa was
obtained in the absence of Cu(acac)2. Tertiary amine might provide a
single electron to alkyl iodide with concomitant generation of alkyl
radical R• and I− under UV light irradiation. (a) Cossy, J.; Ranaivosata,
J.-L.; Bellosta, V. Tetrahedron Lett. 1994, 35, 8161. (b) Kropp, P. J.;
Adkins, R. L. J. Am. Chem. Soc. 1991, 113, 2709. For further discussion
and experimental details, see the Supporting Information.
(8) (a) Huang, H.; Jia, K.; Chen, Y. Angew. Chem., Int. Ed. 2015, 54,
1881. (b) Zhang, J.-J.; Yang, J.-C.; Guo, L.-N.; Duan, X.-H. Chem. - Eur. J.
2017, 23, 10259. (c) Xu, K.; Tan, Z.; Zhang, H.; Liu, J.; Zhang, S.; Wang,
Z. Chem. Commun. 2017, 53, 10719. (d) Zhu, Y.; Gong, J.; Wang, Y. J.
Org. Chem. 2017, 82, 7428. (e) Zhang, Y.; Du, H.; Zhu, M.; Li, J.; Zou,
D.; Wu, Y.; Wu, Y. Tetrahedron Lett. 2017, 58, 880.
(9) For leading reviews, see: (a) Prier, C. K.; Rankic, D. A.; MacMillan,
D. W. C. Chem. Rev. 2013, 113, 5322. (b) Ravelli, D.; Protti, S.; Fagnoni,
M. Chem. Rev. 2016, 116, 9850.
D
DOI: 10.1021/acs.orglett.7b03289
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