Directing Group in Decarboxylative Cross-Coupling: Copper-Catalyzed Site-Selective C-N Bond Formation from Nonactivated Aliphatic Carboxylic Acids

Article abstract of DOI:10.1021/jacs.6b05788

Copper-catalyzed directed decarboxylative amination of nonactivated aliphatic carboxylic acids is described. This intramolecular C-N bond formation reaction provides efficient access to the synthesis of pyrrolidine and piperidine derivatives as well as the modification of complex natural products. Moreover, this reaction presents excellent site-selectivity in the C-N bond formation step through the use of directing group. Our work can be considered as a big step toward controllable radical decarboxylative carbon-heteroatom cross-coupling.

Full text of DOI:10.1021/jacs.6b05788

Article
pubs.acs.org/JACS
Directing Group in Decarboxylative Cross-Coupling: Copper-
Catalyzed Site-Selective C−N Bond Formation from Nonactivated
Aliphatic Carboxylic Acids
Zhao-Jing Liu, Xi Lu, Guan Wang, Lei Li, Wei-Tao Jiang, Yu-Dong Wang, Bin Xiao,* and Yao Fu*
Hefei National Laboratory for Physical Sciences at the Microscale, iChEM, CAS Key Laboratory of Urban Pollutant Conversion,
Anhui Province Key Laboratory of Biomass Clean Energy, University of Science and Technology of China, Hefei 230026, China
S
* Supporting Information
ABSTRACT: Copper-catalyzed directed decarboxylative ami-
nation of nonactivated aliphatic carboxylic acids is described.
This intramolecular C−N bond formation reaction provides
efficient access to the synthesis of pyrrolidine and piperidine
derivatives as well as the modification of complex natural
products. Moreover, this reaction presents excellent site-
selectivity in the C−N bond formation step through the use of
directing group. Our work can be considered as a big step
toward controllable radical decarboxylative carbon−heteroatom cross-coupling.
Scheme 1. Transition Metals in Decarboxylative Carbon−
Heteroatom Cross-Coupling Reactions
1. INTRODUCTION
The use of carboxylic acids, especially for nonactivated aliphatic
carboxylic acids, as “cross-coupling” partners is gaining
increasing attention recent years.1 There are various factors
that contribute to making nonactivated aliphatic carboxylic
acids potentially useful for utilization in organic synthesis and
industrial production: abundant resources (e.g., natural
products and biomass resources) and their natural properties
(e.g., air- and moisture-stable).2−4 On the other hand, aliphatic
carbon−heteroatom bonds are ubiquitous in biologically active
molecules, such as natural products and drugs.5 Therefore, an
efficient approach for the construction of aliphatic carbon−
heteroatom bonds via a transition-metal-catalyzed decarbox-
ylative reaction would be useful and user-friendly.3
The earliest decarboxylative coupling reaction of aliphatic
carboxylic acids to construct carbon−heteroatom bonds dates
back to the Hunsdiecker reaction.6 The disadvantage of this
reaction, however, is the required use of stoichiometric
quantities of silver salts, which then makes the reaction
expensive and environmentally unfriendly. In 2012, Li and co-
workers reported the silver-catalyzed decarboxylative radical
chlorination reaction as the pioneer work of the catalytic
Hunsdiecker reaction.3a Shortly thereafter, they successfully
when there is more than one possible coupling site, difficulties
arise regarding the selectivity of the coupling reaction.
To achieve controllable site-selectivity for decarboxylative
carbon−heteroatom coupling reactions, we introduced the
“directing” concept to facilitate the transition metal catalyst
participating in the subsequent coupling process.7 We expected
that by using a directing group, which has strong coordinating
ability for catalysts, instead of simple protecting groups, we
might achieve our goal (Scheme 1c). The directing group
would enhance the coupling process to take place on a certain
site through the proximity of the catalyst center with the
coupling site. It should be noted that directing groups have
been widely used in the field of transition-metal-catalyzed C−H
functionalization to control the site-selectivity (Scheme 1b).7 A
closely related example is the picolinamide (PA)-directed
3f
constructed aliphatic C−F3b and C−N3 bonds with a slightly
modified catalytic system. Shen and co-workers have also
reported the silver-catalyzed decarboxylative trifluoromethylth-
iolation reaction to construct aliphatic C−S bonds.3c In the
above reactions, aliphatic carboxylic acids were converted to
radical species, promoted by the transition metal catalysts.
However, in the subsequent coupling processes, the generated
alkyl radicals did not coordinate to the metal catalysts (Scheme
1a).3 Therefore, the chemoselectivity of these reactions could
not be controlled by transition metal catalysts. Specifically,
Received: June 6, 2016
© XXXX American Chemical Society
A
DOI: 10.1021/jacs.6b05788
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Journal of the American Chemical Society
Article
intramolecular C(sp3)−H amination reaction, recently devel-
oped by Daugulis8 and Chen.9 They reported on the excellent
control of site-selectivity, which now provides access to N-
containing heterocyclic compounds.10
(entries 6−7, Table 1) and made a critical finding that PhIO
was suitable for this reaction and it was better to add it in two
batches (entry 8, Table 1).12 Under optimal conditions, the GC
yield was 73%. We also noticed that the reaction was completed
within 4 h (entry 9, Table 1). With control experiments, we
found that the reaction did not take place when Cu(OTf)2 was
replaced by Pd, Ni, or Ag salts (entries 10−12, Table 1).
Finally, we found that when the protecting group PA was
replaced by Bz, the desired cyclization reaction was almost
suppressed (entry 13, Table 1).
Herein, we report on the copper-catalyzed intramolecular
decarboxylative amination reaction of nonactivated aliphatic
carboxylic acids. This reaction presents the first example of a
directed decarboxylative C−N bond formation reaction. In this
study, the concept of using a directing group in C−H
functionalization reaction was successfully introduced to
decarboxylative carbon−heteroatom cross-coupling reaction.
This new combination of two important concepts realized
complete site-selectivity in the presence of more than one
potential radical acceptor for the decarboxylative carbon−
heteroatom cross-coupling reaction. Our work demonstrated
that a copper catalyst played an important role in this
decarboxylative C−N coupling reaction. This is a big step
toward achieving controllable radical decarboxylative carbon−
heteroatom cross-coupling with a transition metal catalyst.
Furthermore, most remote amino carboxylic acids are prepared
from cyclic ketones via the classic Beckmann rearrangement
reaction,11 followed by hydrolytic ring opening. Our reaction
would not only be beneficial for the transformation of remote
amino carboxylic acids but also extend the application of classic
Beckmann rearrangement reaction.
With the optimal reaction conditions in hand, we examined
the substrate scope of this decarboxylative C−N coupling
reaction (Table 2). This new catalysis strategy was efficient for
Table 2. Scope of Copper-Catalyzed Intramolecular
Decarboxylative C−N Coupling of Primary Aliphatic
a,b
Carboxylic Acids
2. RESULTS AND DISCUSSION
At the commencement of our work, 5-aminovaleric acid was
selected for our model reaction. (It is commercially available
and easily derived from cyclopentanone.) The PA group was
used as the directing group. The desired product 2a was
obtained in 43% GC yield when using Cu(OTf)2 and pyridine
as the catalyst system, and PhIO as oxidant (entry 2, Table 1).
This finding encouraged us to examine pyridine family additives
(entries 3−5, Table 1). 4-Dimethylaminopyridine (DMAP)
performed best and the yield increased significantly to 64%
(entry 5, Table 1). Furthermore, we screened several oxidants
Table 1. Optimization of the Reaction Conditions for 2a
a
Reaction conditions: 1 (0.2 mmol), Cu(OTf)2 (10 mol %), DMAP
(30 mol %), PhIO (0.2 mmol ×2), CH2Cl2 (0.5 mL), 100 °C, 4 h.
Isolated yield.
catalyst
(10 mol %)
additive
(30 mol %)
oxidant
(2.0 equiv)
GC yield
(%)
a
entry
b
1
2
3
4
5
6
7
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Pd(OAc)2
Ni(OTf)2
AgNO3
-
PhIO
PhIO
PhIO
PhIO
PhIO
K2S2O8
H5IO6
PhIO
PhIO
PhIO
PhIO
PhIO
PhIO
trace
43
8
Pyridine
4-CF3-Pyridine
2,4,6-Collidine
DMAP
construction of 5- and 6-membered heterocycles (e.g., 2a and
2b); however, it did not enable construction of 4- or 7-
membered heterocycles. We also noted that a substrate
containing aryl bromide (2c) was well tolerated in this reaction.
This feature provided additional opportunities for further
functionalization. Substrates with sterically bulky groups at the
α position of the amino group converted to desired products
smoothly (2d−2g). The absolute configuration at the α
position of amino group in compound 2h was retained during
the transformation. Our protocol therefore provides a new
method for the synthesis of chiral pyrrolidine and piperidine
derivatives, which are common chemical skeletons in drugs and
natural products (e.g., Relpax, an antimigraine medication). It
should be noted that the preparation of six-membered ring
products (2i−2l), which could be easily synthesized via this
35
64
0
DMAP
DMAP
0
b
8
DMAP
73
75
0
b
,
c
9
DMAP
10
11
12
13
DMAP
DMAP
0
DMAP
0
d
Cu(OTf)2
DMAP
trace
a
Reaction conditions: 1a (0.2 mmol), CH2Cl2 (0.5 mL), 100 °C, 12 h.
b
c
PhIO was added in two batches. The reaction was carried out for 4
d
h. The protecting group PA was replaced by Bz.
B
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Journal of the American Chemical Society
Article
newly developed reaction, was rather difficult to achieve by C−
cyclic ketones to cyclic amines, which, to date, was extremely
difficult to achieve.16
H activation reaction8,9 or the classic Hofmann−Loffler
̈
reaction.13 Similarly, fused-ring (2m−2r) and spiro-ring (2p)
structures were also easily prepared in the presence of
synthetically important functional groups, such as sulfonamide
(2m) and lactone (2p) groups.
In addition to primary aliphatic carboxylic acids, secondary
aliphatic carboxylic acids can also undergo this transformation
smoothly with moderate yields (Table 3; 2s−2v). However, the
Another interesting, and common, transformation applicable
to natural products was that six-membered cyclic α,β-enones
could be oxidized to δ-carbonyl carboxylic acids in the role of
sodium periodate15b and, subsequently, the carbonyl group
converted to an amino group via a reductive amination
reaction. Following the above methods, the carboxylic acid 1z
was obtained from testosterone benzoate in 52% overall yield
(for more details, see Supporting Information). This amino
acid was converted to the desired cyclic amine 2z in 64% yield
(Scheme 2b). Furthermore, single-crystal X-ray diffraction data
of 2z confirmed that the chemical skeleton of testosterone was
fully maintained during our modification process.
Table 3. Scope of Copper-Catalyzed Intramolecular
Decarboxylative C−N Coupling of Secondary and Tertiary
a,b
Aliphatic Carboxylic Acids
C-alkyl glycosides are important bioactive candidates. It
would therefore be interesting to use our new reaction to
modify C-alkyl glycosides to form more complex structures.15c,d
Under our optimal reaction conditions, C-alkyl glycoside 1a′
was converted to the cyclization product 2a′ in 60% yield
(Scheme 3a). Furthermore, the substrate 1b′, which was
Scheme 3. Modification of Carbohydrate Derivatives
a
Reaction conditions: 1 (0.2 mmol), Cu(OTf)2 (10 mol %), DMAP
(30 mol %), PhIO (0.2 mmol ×2), CH2Cl2 (0.5 mL), 100 °C, 4 h.
b
Isolated yield.
diastereocontrol of this reaction was not good enough when
using secondary aliphatic carboxylic acid 1v, which has a
diastereoisomeric ratio of 1:1, but the product 2v was formed in
42% yield and only with a trans/cis ratio of 2.5:1. Besides, the
attempt to construct six-membered ring product 2w by using
secondary aliphatic carboxylic acid 1w was unsuccessful, we
suspect that this is probably as a result of the steric hindrance
and instability of seven-membered ring intermediate. For
tertiary aliphatic carboxylic acid, the attempt to get even for
the five-membered ring product 2x was failed.
We then utilized this newly developed decarboxylative C−N
coupling reaction for the modification of chemical skeletons in
biologically interesting compounds14,15 (Scheme 2). Estrone
was easily transformed to the corresponding carboxylic acid 1y
through a Beckmann rearrangement reaction.11,15a It was then
converted to the desired product 2y with an isolated yield of
73% (Scheme 2a). Overall, we accomplished the conversion of
derived from R-glyceraldehyde-acetonide, can be transformed
into 2b′ in 52% yield with the protecting group acetonide well
tolerated, which is a frequently used protecting group in
carbohydrate chemistry (Scheme 3b). These transformations
demonstrated the high degree of functional group compatibility
of our newly developed reaction. We therefore expect that this
new C−N coupling reaction will find many applications in
carbohydrate chemistry.
To obtain insight into the mechanism of this decarboxylative
C−N coupling reaction, several control experiments were
carried out. The model reaction was completely shut down
when Cu(OTf)2 was absent or PhIO was not added (1 equiv
Cu(OTf)2 was used instead of PhIO as oxidant). Meanwhile,
starting materials were fully recovered (eq 1), indicating that
the copper-catalyst might be necessary for the decarboxylation
step, although the specific contribution was not clear.
Scheme 2. Modification of Steroidal Compounds
C
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Article
Scheme 4. Proposed Mechanistic Cycle
A radical trapping experiment using TEMPO (2,2,6,6-
tetramethylpiperidinooxy) as radical scavenger was also carried
out (eq 2). The present reaction was completely shut down,
with the quantitative formation of 3a. Finally, we examined the
decarboxylative C−N coupling reaction of a cyclopropyl-
derived carboxylic acid 1c′. In this reaction, the ring-opening
rearrangement product 2c′ was obtained as a single product in
43% isolated yield (eq 3).
out to verify our ideas (Scheme 5a). For each of the substrates,
a single product was observed (2d′a and 2d′b); hence, the
With the above mechanism experiments in hand as well as
the guidance of important literature, we tried to carry out the
proposed mechanism. A closely related work was reported by
Minakata’s group as a hypervalent iodine(III)-mediated
oxidative decarboxylation of β,γ-unsaturated carboxylic acid to
construct C−N bonds, which is of significantly broad substrate
scopem and lack of metal catalyst made this reaction
synthetically useful.3i The mechanistic study suggested that an
ionic oxidative decarboxylation process was involved, in which
the formation of allyl-λ3-iodane intermediate was crucial.
However, the formation of allyl-λ3-iodane intermediate was
not a suitable pathway for explaining our reaction which uses
nonactivated alkyl carboxylic acids.
Scheme 5. Site-Selectivity Controlled by a Directing Group
(PA)
Another decarboxylation mechanism involves a SET (single
electron transfer) process of an ion-pair which was produced
via heterolytic cleavage of one I−O bond of (diacyloxyiodo)-
benzene.2b,c This process must be triggered by low-valence
copper species (e.g., CuI) other than CuII(OTf)2 at the initial
stage of the reaction.17 Moreover, two copper species were
required to work in parallel to maintain the catalysis
proceeding, which could not be supported by the research
data on the relationship between copper concentration and
yield,18 making this mechanism inconsequential.
According to the recent work reported by Maruoka’s
group,19 a more reasonable mechanism was carried out and
shown in Scheme 4. In the presence of CuII-L, 1a reacts with
PhIO to form hypervalent iodine(III) intermediate I,20,21 which
undergoes a homolytic cleavage of one I−O bond to produce
two radical intermediates II and III at 100 °C.19 The
intermediate II goes through a decarboxylation process to
generate an alkyl radical intermediate IV and releases CO2.
Then, by oxidative addition of the alkyl radical to the CuII
which is chelated by the directing group, intermediate V is
generated.22 Followed by reductive elimination, the desired
product 2a is produced and the intermediate CuI-L is released
simultaneously. Finally, the whole catalytic cycle is accom-
plished with the intermediate CuI-L oxidized to CuII-L by
intermediate III or decomposition products thereof.23
coupling process took place on the PA-protected amino group
selectively. The selectivity of this reaction was determined by
the N-protecting groups (Bz or PA) on the substrates. The size
of newly forming rings would not affect the site-selectivity. As
mentioned above, the alkyl carboxylic acid was converted to an
alkyl radical species and trapped by radical acceptors. In terms
of the ability to capture free radicals, there is no essential
difference between BzNH and PANH as they have similar
arylamide structures. Furthermore, we tested the comparative
experiment between TsNH and PANH (Scheme 5b). Similarly,
we only got the product cyclized at the PANH side. We believe
that chelation of the PA-protected amino group promotes the
metal to participate further in the coupling process after the
decarboxylation step. Results of these comparative experiments
indicated that control of the reaction selectivity is due to the
“directing” concept.
3. CONCLUSION
To summarize, we report the first Cu-catalyzed intramolecular
decarboxylative C−N coupling of nonactivated aliphatic
carboxylic acids. The concept of a directing group is introduced
to decarboxylative carbon−heteroatom cross-coupling reaction
for the control of site-selectivity. Remote amino carboxylic
As an important component of this study, efforts were
devoted to the control of selectivity in the coupling process by
using a directing group. Comparative experiments were carried
D
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(2) For selected examples of C−C bond formation via decarbox-
ylative cross-coupling of nonactivated aliphatic carboxylic acids: (a) Liu,
X.; Wang, Z.; Cheng, X.; Li, C. J. Am. Chem. Soc. 2012, 134, 14330.
(b) Xie, J.; Xu, P.; Li, H.; Xue, Q.; Jin, H.; Cheng, Y.; Zhu, C. Chem.
Commun. 2013, 49, 5672. (c) Wang, Y.; Zhang, L.; Yang, Y.; Zhang, P.;
Du, Z.; Wang, C. J. Am. Chem. Soc. 2013, 135, 18048. (d) Noble, A.;
McCarver, S. J.; MacMillan, D. W. C. J. Am. Chem. Soc. 2015, 137, 624.
(e) Zhou, Q.-Q.; Guo, W.; Ding, W.; Wu, X.; Chen, X.; Lu, L.-Q.;
Xiao, W.-J. Angew. Chem., Int. Ed. 2015, 54, 11196. (f) Premi, C.; Dixit,
A.; Jain, N. Org. Lett. 2015, 17, 2598.
acids could be easily obtained from the transformation of
natural products. Therefore, this newly developed reaction
provides an efficient approach for the late-stage modification of
some core structures. Of particular note is that, in the presence
of a directing group, a copper catalyst plays an important role in
the C−N bond formation step. It is the basis of the controllable
site-selectivity of this reaction. Our work may also be
considered as a big step toward controllable radical
decarboxylative carbon−heteroatom cross-coupling.
(3) For selected examples of C−heteroatom bond formation via
decarboxylative cross-coupling of nonactivated aliphatic carboxylic
acids: (a) Wang, Z.; Zhu, L.; Yin, F.; Su, Z.; Li, Z.; Li, C. J. Am. Chem.
Soc. 2012, 134, 4258. (b) Yin, F.; Wang, Z.; Li, Z.; Li, C. J. Am. Chem.
Soc. 2012, 134, 10401. (c) Hu, F.; Shao, X.; Zhu, D.; Lu, L.; Shen, Q.
Angew. Chem., Int. Ed. 2014, 53, 6105. (d) Wang, P.-F.; Wang, X.-Q.;
Dai, J.-J.; Feng, Y.-S.; Xu, H.-J. Org. Lett. 2014, 16, 4586. (e) Ventre, S.;
Petronijevic, F. R.; MacMillan, D. W. C. J. Am. Chem. Soc. 2015, 137,
5654. (f) Liu, C.; Wang, X.; Li, Z.; Cui, L.; Li, C. J. Am. Chem. Soc.
2015, 137, 9820. (g) Zhu, Y.; Li, X.; Wang, X.; Huang, X.; Shen, T.;
Zhang, Y.; Sun, X.; Zou, M.; Song, S.; Jiao, N. Org. Lett. 2015, 17,
4702. For selected examples of C−N bond formation via
decarboxylative cross-coupling of activated carboxylic acids:
(h) Zhang, Y.; Patel, S.; Mainolfi, N. Chem. Sci. 2012, 3, 3196.
(i) Kiyokawa, K.; Yahata, S.; Kojima, T.; Minakata, S. Org. Lett. 2014,
16, 4646. (j) Sheng, W.-J.; Ye, Q.; Yu, W.-B.; Liu, R.-R.; Xu, M.; Gao,
J.-R.; Jia, Y.-X. Tetrahedron Lett. 2015, 56, 599.
4. EXPERIMENTAL SECTION
General Procedure for Copper-Catalyzed Intramolec-
ular Decarboxylative C−N Coupling of Aliphatic
Carboxylic Acids. To a 10 mL thick-walled pressure tube
was sequentially added Cu(OTf)2 (7.2 mg, 0.02 mmol), DMAP
(7.3 mg, 0.06 mmol), 1 (0.2 mmol), PhIO (44 mg, 0.2 mmol),
and 0.5 mL of CH2Cl2. The tube was sealed with a Teflon lined
cap and the reaction mixture was stirred at 100 °C for 1 h. After
cooling to room temperature, another portion of PhIO (44 mg,
0.2 mmol) was added and the reaction mixture was stirred at
100 °C for another 3 h. After complete consumption of 1 (the
reaction progress was monitored by TLC; for some substrates
with slower reaction rate, it is necessary to prolong the reaction
time), the product 2 could be obtained by silica gel column
chromatography.
(4) For a selected review of aliphatic acids: Harwood, H. J. Chem.
Rev. 1962, 62, 99.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/jacs.6b05788.
(5) (a) Hartmann, R. W.; Hector, M.; Wachall, B. G.; Palusczak, A.;
Palzer, M.; Huch, V.; Veith, M. J. Med. Chem. 2000, 43, 4437.
(b) Taylor, R. D.; MacCoss, M.; Lawson, A. D. G. J. Med. Chem. 2014,
57, 5845.
(6) (a) Hunsdiecker, H.; Hunsdiecker, C. Ber. Dtsch. Chem. Ges. B
1942, 75B, 291;(b) Hunsdiecker, H.; Hunsdiecker, C.; Vogt, E. U.S.
Patent 2,176,181, 1939; Chem. Abstr. 1940, 34, 1685. (c) Cristol, S. J.;
Firth, W. C., Jr. J. Org. Chem. 1961, 26, 280. (d) Kochi, J. K. J. Am.
Chem. Soc. 1965, 87, 2500. (e) Kochi, J. K. J. Org. Chem. 1965, 30,
3265. (f) Kochi, J. K. Science 1967, 155, 415. (g) McKillop, A.;
Bromley, D.; Taylor, E. C. J. Org. Chem. 1969, 34, 1172.
■
S
Experimental details and compound characterizations
(PDF)
Crystallographic data (CIF)
Crystallographic data (CIF)
Crystallographic data (CIF)
(7) For selected reviews of directed C−H functionalization:
(a) Ackermann, L.; Vicente, R.; Kapdi, A. R. Angew. Chem., Int. Ed.
2009, 48, 9792. (b) Chen, X.; Engle, K. M.; Wang, D.-H.; Yu, J.-Q.
Angew. Chem., Int. Ed. 2009, 48, 5094. (c) Daugulis, O.; Do, H.-Q.;
Shabashov, D. Acc. Chem. Res. 2009, 42, 1074. (d) Colby, D. A.;
Bergman, R. G.; Ellman, J. A. Chem. Rev. 2010, 110, 624. (e) Lyons, T.
W.; Sanford, M. S. Chem. Rev. 2010, 110, 1147. (f) Wencel-Delord, J.;
AUTHOR INFORMATION
■
Corresponding Authors
*E-mail: binxiao@ustc.edu.cn.
*E-mail: fuyao@ustc.edu.cn.
Notes
Droge, T.; Liu, F.; Glorius, F. Chem. Soc. Rev. 2011, 40, 4740.
̈
The authors declare no competing financial interest.
(g) Engle, K. M.; Mei, T.-S.; Wasa, M.; Yu, J.-Q. Acc. Chem. Res. 2012,
45, 788. (h) Daugulis, O.; Roane, J.; Tran, L. D. Acc. Chem. Res. 2015,
48, 1053.
ACKNOWLEDGMENTS
■
(8) Nadres, E. T.; Daugulis, O. J. Am. Chem. Soc. 2012, 134, 7.
(9) He, G.; Zhao, Y.; Zhang, S.; Lu, C.; Chen, G. J. Am. Chem. Soc.
2012, 134, 3.
(10) For selected examples of saturated N-heterocycles synthesis via
transition metal catalyzed C−N bond formation reaction: (a) Fix, S.
R.; Brice, J. L.; Stahl, S. S. Angew. Chem., Int. Ed. 2002, 41, 164.
This work was supported by the 973 Program
(2012CB215306), NSFC (21325208, 21361140372,
21572212, 21302178, 21472181), CAS (YZ201563),
IPDFHCPST (2014FXCX006), FRFCU, PCSIRT and Youth
Innovation Promotion Association of the Chinese Academy of
Sciences (2015371).
(b) Streuff, J.; Hovelmann, C. H.; Nieger, M.; Muniz, K. J. Am. Chem.
̈
̃
Soc. 2005, 127, 14586. (c) Muniz, K.; Hovelmann, C. H.; Streuff, J. J.
̃
̈
REFERENCES
Am. Chem. Soc. 2008, 130, 763. (d) Wu, T.; Yin, G.; Liu, G. J. Am.
Chem. Soc. 2009, 131, 16354. (e) Zhao, B.; Du, H.; Cui, S.; Shi, Y. J.
Am. Chem. Soc. 2010, 132, 3523. (f) Sequeira, F. C.; Turnpenny, B.
W.; Chemler, S. R. Angew. Chem., Int. Ed. 2010, 49, 6365. (g) Bovino,
M. T.; Chemler, S. R. Angew. Chem., Int. Ed. 2012, 51, 3923.
(h) Ingalls, E. L.; Sibbald, P. A.; Kaminsky, W.; Michael, F. E. J. Am.
Chem. Soc. 2013, 135, 8854. (i) Egami, H.; Kawamura, S.; Miyazaki, A.;
Sodeoka, M. Angew. Chem., Int. Ed. 2013, 52, 7841. (j) Vo, C.-V. T.;
Bode, J. W. J. Org. Chem. 2014, 79, 2809. (k) Siau, W.-Y.; Bode, J. W. J.
Am. Chem. Soc. 2014, 136, 17726. (l) Lindsay, V. N. G.; Viart, H. M.-
■
(1) For selected reviews of decarboxylative cross-coupling reactions:
(a) Gooßen, L. J.; Rodríguez, N.; Gooßen, K. Angew. Chem., Int. Ed.
2008, 47, 3100. (b) Weaver, J. D.; Recio, A.; Grenning, A. J.; Tunge, J.
A. Chem. Rev. 2011, 111, 1846. (c) Rodríguez, N.; Goossen, L. J.
Chem. Soc. Rev. 2011, 40, 5030. (d) Shang, R.; Liu, L. Sci. China: Chem.
2011, 54, 1670. (e) Cornella, J.; Larrosa, I. Synthesis 2012, 44, 653.
(f) Dzik, W. I.; Lange, P. P.; Gooßen, L. J. Chem. Sci. 2012, 3, 2671.
(g) Park, K.; Lee, S. RSC Adv. 2013, 3, 14165. (h) Shen, C.; Zhang, P.;
Sun, Q.; Bai, S.; Hor, T. S. A.; Liu, X. Chem. Soc. Rev. 2015, 44, 291.
E
DOI: 10.1021/jacs.6b05788
J. Am. Chem. Soc. XXXX, XXX, XXX−XXX

Journal of the American Chemical Society
Article
F.; Sarpong, R. J. Am. Chem. Soc. 2015, 137, 8368. (m) Martínez, C.;
Muniz, K. Angew. Chem., Int. Ed. 2015, 54, 8287.
̃
(11) (a) Beckmann, E. Ber. Dtsch. Chem. Ges. 1886, 19, 988.
(b) Nguyen, M. T.; Raspoet, G.; Vanquickenborne, L. G. J. Am. Chem.
Soc. 1997, 119, 2552.
(12) For a review with the PhIO-DCM oxidant system summarized
comprehensively: Zhdankin, V. V.; Stang, P. J. Chem. Rev. 2008, 108,
5299.
(13) (a) Wawzonek, S.; Nelson, M. F.; Thelen, P. J. J. Am. Chem. Soc.
1951, 73, 2806. (b) Wolff, M. E. Chem. Rev. 1963, 63, 55.
(c) Wawzonek, S.; Wilkinson, T. C. J. Org. Chem. 1966, 31, 1732.
(14) For a review of natural product chemistry in drug discovery:
Butler, M. S. J. Nat. Prod. 2004, 67, 2141.
(15) (a) Regan, B. M.; Hayes, F. N. J. Am. Chem. Soc. 1956, 78, 639.
(b) Lingham, R. B.; Silverman, K. C.; Jayasuriya, H.; Kim, B. M.; Amo,
S. E.; Wilson, F. R.; Rew, D. J.; Schaber, M. D.; Bergstrom, J. D.;
Koblan, K. S.; Graham, S. L.; Kohl, N. E.; Gibbs, J. B.; Singh, S. B. J.
Med. Chem. 1998, 41, 4492. (c) Wakabayashi, T.; Shiozaki, M.;
Kurakata, S. Carbohydr. Res. 2002, 337, 97. (d) Zhao, C.; Jia, X.; Wang,
X.; Gong, H. J. Am. Chem. Soc. 2014, 136, 17645. (e) Taber, D. F.;
Deker, P. B.; Fales, H. M.; Jones, T. H.; Lloyd, H. A. J. Org. Chem.
1988, 53, 2968. (f) Zheng, Y.; Avery, M. A. Tetrahedron 2004, 60,
2091 Detailed transformation processes of these natural products are
given in the Supporting Information..
(16) Formally, this reaction may also be considered as a ring
contraction reaction starting from a six-membered cyclic amide to get
a five-membered pyrrolidine product. See Supporting Information for
detailed transformation.
(17) For a review of single electron transfer process: Zhang, N.;
Samanta, S. R.; Rosen, B. M.; Percec, V. Chem. Rev. 2014, 114, 5848.
(18) See Supporting Information for details.
(19) Sakamoto, R.; Inada, T.; Selvakumar, S.; Moteki, S. A.; Maruoka,
K. Chem. Commun. 2016, 52, 3758.
(20) For selected examples of PhIO reacted with carboxylic acids:
(a) Pausacker, K. H. J. Chem. Soc. 1953, 107. (b) Bell, R.; Morgan, K. J.
J. Chem. Soc. 1960, 1209. (c) Leffler, J. E.; Story, L. J. J. Am. Chem. Soc.
1967, 89, 2333. (d) Leffler, J. E.; Ward, D. C.; Burduroglu, A. J. Am.
Chem. Soc. 1972, 94, 5339.
(21) For selected examples of copper-catalyzed reactions using PA or
́
other N,N-bidentate directing groups: (a) Martínez, A. M.; Rodríguez,
N.; Arrayas, R. G.; Carretero, J. C. Chem. Commun. 2014, 50, 2801.
́
(b) Li, Q.; Zhang, S.-Y.; He, G.; Ai, Z.; Nack, W. A.; Chen, G. Org.
Lett. 2014, 16, 1764. (c) Takamatsu, K.; Hirano, K.; Satoh, T.; Miura,
M. Org. Lett. 2014, 16, 2892. (d) Takamatsu, K.; Hirano, K.; Satoh, T.;
Miura, M. J. Org. Chem. 2015, 80, 3242. (e) Liu, Y.-J.; Liu, Y.-H.; Yin,
X.-S.; Gu, W.-J.; Shi, B.-F. Chem. - Eur. J. 2015, 21, 205. (f) Miura, W.;
Hirano, K.; Miura, M. Org. Lett. 2015, 17, 4034.
(22) For selected examples of carbon-centered radicals captured by
Cu catalysts: (a) Kochi, J. K.; Bemis, A.; Jenkins, C. L. J. Am. Chem.
Soc. 1968, 90, 4616. (b) King, A. E.; Huffman, L. M.; Casitas, A.;
Costas, M.; Ribas, X.; Stahl, S. S. J. Am. Chem. Soc. 2010, 132, 12068.
(c) Casitas, A.; King, A. E.; Parella, T.; Costas, M.; Stahl, S. S.; Ribas,
̀
X. Chem. Sci. 2010, 1, 326. (d) Casitas, A.; Poater, A.; Sola, M.; Stahl,
S. S.; Costas, M.; Ribas, X. Dalton Trans. 2010, 39, 10458.
(e) Huffman, L. M.; Casitas, A.; Font, M.; Canta, M.; Costas, M.;
Ribas, X.; Stahl, S. S. Chem. - Eur. J. 2011, 17, 10643.
(23) Note that Reutov group has discovered that the rearrangements
of alkyl radicals via 1,2-hydrogen shift almost could not be detected
compared with alkyl cations: Reutov, O. A. Pure Appl. Chem. 1963, 7,
203 Therefore, our reaction is most likely to take place via a radical
process because no cationic rearrangement product was detected when
primary carboxylic acid was employed (e.g., 2b, Table 2)..
F
DOI: 10.1021/jacs.6b05788
J. Am. Chem. Soc. XXXX, XXX, XXX−XXX