Decarboxylative C(sp3)?N cross-coupling of diacyl peroxides with nitrogen nucleophiles

Article abstract of DOI:10.1021/acs.orglett.0c04203

We have disclosed a new radical-mediated decarboxylative C(sp³)?N cross-coupling of diacyl peroxides with nitrogen nucleophiles. The primary and secondary alkyl radicals derived from corresponding diacyl peroxides were generated by copper catalysis or by merging copper catalysis and photoredox catalysis, respectively. Various N-alkyl nitrogen nucleophiles, including indazoles, triazoles, indoles, purine, carbazole, anilines, and sulfonamide, were provided with a broad substrate scope and good functional group tolerance.

Full text of DOI:10.1021/acs.orglett.0c04203

pubs.acs.org/OrgLett
Letter
Decarboxylative C(sp3)−N Cross-Coupling of Diacyl Peroxides with
Nitrogen Nucleophiles
Zi-Liang Tang, Xuan-Hui Ouyang,* Ren-Jie Song, and Jin-Heng Li*
Cite This: Org. Lett. 2021, 23, 1000−1004
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ABSTRACT: We have disclosed a new radical-mediated decar-
boxylative C(sp3)−N cross-coupling of diacyl peroxides with
nitrogen nucleophiles. The primary and secondary alkyl radicals
derived from corresponding diacyl peroxides were generated by
copper catalysis or by merging copper catalysis and photoredox
catalysis, respectively. Various N-alkyl nitrogen nucleophiles,
including indazoles, triazoles, indoles, purine, carbazole, anilines, and sulfonamide, were provided with a broad substrate scope
and good functional group tolerance.
Scheme 1. Decarboxylative C(sp3)−N Cross-Coupling of
Redox-Active Esters
ver the past decades, the construction of the C−N bond
has always been the field of focus in organic synthesis
O
owing to its important role in pharmaceuticals, natural
products, and agrochemicals.1 The formation of the C(sp3)−
N bond has attracted much attention.2,6−9 Thus many
strategies have been proposed toward the formation of the
C(sp3)−N bond, including coupling a nitrogen nucleophile to
an alkyl electrophile (e.g., aliphatic halides, alcohols),3a,e
reductive amination,3f,g the hydroamination of alkene,3h,i and
the carboamination of alkene.3j,l Whereas great achievements
have been made, such available approaches are still limited by
strong bases, a narrow scope of substrates, a great amount of
waste.
Aliphatic carboxylic acids and their derivatives have low
toxicity and are inexpensive, stable, and readily available in
addition to being widely found in natural products and
pharmaceuticals,4 allowing the radical decarboxylative alkyla-
tion reaction to be a powerful transformation to rapidly
construct C(sp3)−X (X = C, N, O, S, etc.) bonds.5−10 In 2017,
Fu, Peters, and coworkers6 developed a decarboxylative
C(sp3)−N coupling of alkyl N-hydroxyphthalimide (NHPI)
ester to afford alkyl phthalimides by using photoexcitation of a
copper complex to achieve the single-electron reduction
(Scheme 1a). In 2018, Macmillan7 and Hu8 independently
reported dual copper-catalyzed and photoredox-catalyzed
decarboxylative C(sp3)−N coupling by using alkyl N-
hydroxyphthalimide (NHP) ester and iodomesitylene dicar-
boxylates as an alkyl radical precursor, respectively (Scheme
1a). On the basis of these results, masked alkyl carboxylic
acids, such as alkyl NHPI esters9 and iodomesitylene
dicarboxylates,7,10 undergo single-electron reduction in the
presence of photoredox catalysis or transition-metal catalysis to
form an alkyl radical intermediate that easily reacts with the
LnCunX−nitrogen nucleophile complex A (Scheme 1a).
Despite the great achievements in decarboxylative sp3 C−N
coupling, it is still highly desired to realize the construction of
sp3 C−N bonds with a new alkylating reagent. Diacyl peroxides
are a class of redox-active esters that are easily prepared from
aliphatic carboxylic acids and are readily decarboxylated to
provide alkyl radicals under cheap transition-metal catalysis
and heating.11 Inspired by these pioneering works, we
hypothesized that if the oxidizing diacyl peroxides could
generate alkyl radical species in the presence of photoredox
catalysis or copper catalysis, then the alkyl radical species could
further react with LnCunX−nitrogen nucleophile complex A to
build C(sp3)−N bonds (Scheme 1a). Here we have developed
a new decarboxylative C(sp3)−N cross-coupling of diacyl
peroxides with nitrogen nucleophiles (Scheme 1b) to provide
various alkylated nitrogen products, including indazoles,
Received: December 19, 2020
Published: January 21, 2021
https://dx.doi.org/10.1021/acs.orglett.0c04203
© 2021 American Chemical Society
Org. Lett. 2021, 23, 1000−1004
1000

Organic Letters
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Letter
a
triazoles, indoles, purine, carbazole, anilines, sulfonamide, and
other nitrogen nucleophiles.
Scheme 2. Variations of the Nitrogen Nucleophiles (1)
We initially choose 1H-indazole 1a and lauroyl peroxide
(LPO) 2a as the template reaction to investigate the
decarboxylative C(sp3)−N coupling. The desired product
3aa was offered in 96% yield in the presence of CuBr (20 mol
%) and Phen (30 mol %) in 1,4-dioxane under thermal
conditions (Table 1, entry 1). Both copper catalysis and
a
Table 1. Screening of Optimal Reaction Conditions
b
entry
variation from the standard conditions
yield (%)
1
2
3
4
5
6
7
8
none
without CuBr
without Phen
Cu(OTf)2 instead of CuBr
Cu(MeCN)4PF6 instead of CuBr
CuTc instead of CuBr
CuI instead of CuBr
L2 instead of L1
L3 instead of L1
L4 instead of L1
L5 instead of L1
PPh3 instead of L1
MeOH instead of 1,4-dioxane
MeCN instead of 1,4-dioxane
PhMe instead of 1,4-dioxane
DMSO instead of 1,4-dioxane
at room temperature
at 80 °C
96
trace
trace
86
88
93
89
90
50
42
32
21
85
79
64
37
75
91
95
90
9
a
Reaction conditions: 1a (0.2 mmol), 2a (1.5 equiv), CuBr (20 mol
10
11
12
13
14
15
16
17
18
%), Phen (30 mol %), 1,4-dioxane (2 mL), and argon at 60 °C for 12
h.
could smoothly undergo the copper-catalyzed decarboxylative
coupling of lauroyl peroxide to give the alkylated products
3ba−wa in moderate to good yields. Benzimidazole 1b and
indazole 1c were all tolerated, furnishing the alkylated products
in 91 and 71% yields, respectively. Benzotriazole 1d is a
suitable substrate, providing the isomer products 3da and 3da′
in a 1:1 ratio. Heterocycles bearing three nitrogen atoms, such
as triazoles 1e−g, were all converted to N-alkyl products 3ea−
ga in medium yields. Indoles with electron-withdrawing group
were suitable substrates, offering the corresponding products
3ha−ka. Purine and carbazole were compatible with the
reaction system. Benzenesulfonamide and aniline were
successfully reacted with LPO to afford the products 3na
and 3oa in 57 and 56% yields, respectively. Primary anilines
bearing an OMe, an iodo, a chloro, a nitro, or a cyano on the
aromatic ring were suitable nitrogen nucleophiles to deliver the
N-alkyl anilines 3pa−ta in moderate and good yields,
providing the possibility of further modification. However,
secondary anilines 1u,v were coupled to obtain the tertiary
amines 3ua,va in low yields. The nitrogen nucleophile 1x with
multiple sites achieves the regioselective alkylation product
3wa. Unfortunately, the alkyl amine 1x tends to give the
amidation product 4xa in 83% yield. Performing quinoline-8-
amine 1y gave the corresponding target product 3ya in 89 and
62% yields under standard conditions and without ligands,
respectively. Strikingly, the decarboxylation protocol was
applicable to the modification of Celecoxib 1z, providing the
alkylated product 3za in 94% yield.
c
19
20
at room temperature
none
d
a
Reaction conditions: 1a (0.2 mmol), 2a (1.5 equiv), CuBr (20 mol
%), Phen (30 mol %), 1,4-dioxane (2 mL), and argon at 60 °C for 12
h. Isolated yield. [Ir(dtbbpy)(ppy)2]PF6 (1 mol %) 18 W blue LED
for24 h 1a (1 mmol) for 24 h.
b
c
d
nitrogen ligands are indispensable for the decarboxylative
cross-coupling reaction (entries 2 and 3). Other copper
catalysts, such as Cu(OTf)2, Cu(MeCN)4PF6, CuTc, and
Cu(acac)2, can effectively promote the decarboxylative
coupling reaction to obtain the target product 3aa in slightly
lower yields (entry 1 vs entries 4−7). A series of nitrogen
ligands were tested, and other ligands were not as good as
1,10-phenanthroline (L1) (entries 8−12). The optimization of
solvents, including MeOH, MeCN, toluene, and DMSO,
indicates that 1,4-dioxane is the best choice (entries 13−16).
The optimization of the reaction temperature indicates that 60
°C is the best choice (entries 17 and 18). Moreover, we found
that the photoredox catalysis can promote the reaction under
an 18 W blue LED at room temperature, offering the product
3aa in 95% yield (entry 19). Gratifyingly, when the reaction
scale is increased to 1 mmol of 1H-indazole 1a, product 3aa
can still be obtained in 90% yield (entry 20).
We next examined the applicability of decarboxylative
C(sp3)−N cross-coupling by assessing the scope of diacyl
peroxides. As shown in Scheme 3, a variety of diacyl peroxides
derived from alkyl carboxylic acids were tolerated, providing
the N-alkyl products in moderate to good yields. Primary acids
With the optimal reaction conditions in hand, we then
investigated the scope of nitrogen nucleophiles (Scheme 2).
Overall, a wide range of nitrogen nucleophiles, including
nitrogen heterocycles, carbazole, anilines, and sulfonamide,
1001
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Letter
a
Scheme 3. Variations of Diacyl Peroxides (2)
Scheme 4. Control Experiments and Possible Mechanism
Scheme 4. First, copper(I)−amido species B readily forms
through the coordination of copper(I) catalyst A with nitrogen
nucleophile 1. The primary alkyl peroxides 2 easily oxidizes the
intermediate B to produce an alkyl radical and copper(II)−
amido species C by releasing CO2 (path a). On the contrary,
the excited photocatalyst IrIII* could rapidly oxidize copper-
(I)−amido species B to copper(II)−amido species C and
generate the IrII intermediate, which could reduce secondary
alkyl peroxides by a single-electron transfer (SET), affording an
alkyl radical and regenerating IrIII catalysis. Then, the alkyl
radical intermediate reacts with copper(II)−amido species C
to afford the copper(III)−alkyl−amido complex D, which
would undergo reductive elimination to provide N-alkyl
products 3 and to regenerate A. In addition, copper(II)−
amido species C may undergo a direct group transfer in the
presence of the alkyl radical (path c) to afford N-alkyl products
3 and to regenerate A.12i,j
In summary, a new radical-mediated decarboxylative C-
(sp3)−N cross-coupling of diacyl peroxides has been
developed. Copper catalysis or the combination of copper
catalysis and photocatalysis is the key to the generation of
primary and secondary alkyl radicals, respectively. This
protocol has shown mild conditions, good functional group
tolerance, and a broad substrate scope, which provides a new
way to approach a variety of N-alkyl products. The further
application of this strategy is being explored in our laboratory.
a
Reaction conditions: 1a (0.2 mmol), 2a (1.5 equiv), CuBr (20 mol
%), Phen (30 mol %), 1,4-dioxane (2 mL), and argon at 60 °C for 12
b
c
h. At 100 °C. [Ir(dtbbpy)(ppy)2]PF6 (1 mol %) 18 W blue LED at
100 °C for 24 h.
with various alkyl-substituted groups could be smoothly
converted to the desired products 3ab−ae in 50−91% yields.
Primary acids containing a series of functional groups, such as
alkynyl 2f, bromo 2g, carbonyl 2h, and ester 2i, were well
tolerated, offering the corresponding products 3af−ai in 61−
92% yields. The complex natural products, including stearic
acid 2k and oleic acid 2l, were compatible with the reaction to
supply the products 3ak,al in moderate yields. The secondary
alkyl groups, such as cyclobutyl, cyclopentyl, and piperidin-4-
yl, were also investigated under a copper catalyst to afford the
amidation products, whereas the combination of a copper and
photoredox catalyst resulted in decarboxylation products
3am−3ao in 56−75% yields. Unfortunately, tertiary acids
2p−s failed to achieve the decarboxylative coupling of diacyl
peroxides under copper catalysis or dual copper and photo-
redox catalysis. This may be due to the bulky sterically
hindered tertiary alkyl group leading to the amidation products
4ap−as in 57−96% yields.8
To gain mechanistic insights into the decarboxylative cross-
coupling, we carried out some radical-trapping experiments
that add 3 equiv of free-radical scavengers, such as TEMPO,
hydroquinone, and butylated hydroxytoluene (BHT) in the
presence of 1H-indazole 1a and diacyl peroxide 2g under
standard conditions (Scheme 4). The decarboxylative C(sp3)−
N cross-coupling was shut down, and the TEMPO-trapping
product 5a was afforded in 51% yield, indicating that the alkyl
radical was generated under the standard reaction conditions.
Moreover, when quinoline-8-amine was used as the nitrogen
nucleophile, the product 3ya was supplied in the absence of
1,10-phenanthroline, showing that the copper(I)−amido
species had formed.
ASSOCIATED CONTENT
* Supporting Information
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The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.orglett.0c04203.
Descriptions of experimental procedures for compounds
and analytical characterization (PDF)
AUTHOR INFORMATION
Corresponding Authors
■
Xuan-Hui Ouyang − Key Laboratory of Jiangxi Province for
Persistent Pollutants Control and Resources Recycle,
Nanchang Hangkong University, Nanchang 330063, China;
Email: xuanhuiouyang@163.com
Jin-Heng Li − Key Laboratory of Jiangxi Province for
Persistent Pollutants Control and Resources Recycle,
Nanchang Hangkong University, Nanchang 330063, China;
State Key Laboratory of Chemo/Biosensing and
On the basis of the experimental results and previous
literature reports,6−10,12 a plausible mechanism is proposed in
1002
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Org. Lett. 2021, 23, 1000−1004

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Letter
Chem. Soc. Rev. 2020, 49, 1790−1811. (k) Ouyang, X.-H.; Li, Y.;
Song, R.-J.; Li, J.-H. Org. Lett. 2018, 20, 6659−6662. (l) Liu, Y.-Y.;
Yang, X.-H.; Song, R.-J.; Luo, S.; Li, J.-H. Nat. Commun. 2017, 8,
14720.
(4) (a) Maag, H. Prodrugs 2007, V, 703. (b) Lu, S.-Y.; Hamerton, I.
Prog. Polym. Sci. 2002, 27, 1661−1712. (c) Horsman, G. P.; Zechel,
D. L. Chem. Rev. 2017, 117, 5704−5783.
(5) For selected reviews on radical decarboxylative reactions, see:
(a) Huang, H.; Jia, K.; Chen, Y. ACS Catal. 2016, 6, 4983. (b) Zheng,
Y.; Shao, X.-Q.; Ramadoss, V.; Tian, L.-F.; Wang, Y.-H. Synthesis
2020, 52, 1357−1368. (c) Li, Y.; Ge, L.; Muhammad, M. T.; Bao, H.
Synthesis 2017, 49, 5263. (d) Jin, Y.; Fu, H. Asian J. Org. Chem. 2017,
6, 368. (e) Xuan, J.; Zhang, Z.-G.; Xiao, W.-J. Angew. Chem., Int. Ed.
2015, 54, 15632.
Chemometrics, Hunan University, Changsha 410082, China;
State Key Laboratory of Applied Organic Chemistry,
Lanzhou University, Lanzhou 730000, China; orcid.org/
0000-0001-7215-7152; Email: jhli@hnu.edu.cn
Authors
Zi-Liang Tang − Key Laboratory of Jiangxi Province for
Persistent Pollutants Control and Resources Recycle,
Nanchang Hangkong University, Nanchang 330063, China
Ren-Jie Song − Key Laboratory of Jiangxi Province for
Persistent Pollutants Control and Resources Recycle,
Nanchang Hangkong University, Nanchang 330063, China;
State Key Laboratory of Chemo/Biosensing and
(6) Zhao, W.; Wurz, R. P.; Peters, J. C.; Fu, G. C. J. Am. Chem. Soc.
2017, 139, 12153.
(7) Liang, Y.-F.; Zhang, X.-H.; MacMillan, D. W. C. Nature 2018,
559, 83.
Chemometrics, Hunan University, Changsha 410082,
China; orcid.org/0000-0001-8708-7433
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.orglett.0c04203
(8) Mao, R.; Frey, A.; Balon, J.; Hu, X. Nat. Catal. 2018, 1, 120.
(9) (a) Kong, W.; Yu, C.; An, H.; Song, Q. Org. Lett. 2018, 20, 349.
(b) Wang, G.-Z.; Shang, R.; Fu, Y. Org. Lett. 2018, 20, 888. (c) Shen,
M.-L.; Shen, Y.; Wang, P.-S. Org. Lett. 2019, 21, 2993. (d) Yang, J.;
Zhang, J.; Qi, L.; Hu, C.; Chen, Y. Chem. Commun. 2015, 51, 5275.
(e) Hu, C.; Chen, Y. Org. Chem. Front. 2015, 2, 1352. (f) Zhang, J.-J.;
Yang, J.-C.; Guo, L.-N.; Duan, X.-H. Chem. - Eur. J. 2017, 23, 10259.
(g) Shibutani, S.; Kodo, T.; Takeda, M.; Nagao, K.; Tokunaga, N.;
Sasaki, Y.; Ohmiya, H. J. Am. Chem. Soc. 2020, 142, 1211. (h) Zheng,
C.; Wang, Y.-T.; Xu, Y.-R.; Chen, Z.; Chen, G.-Y.; Liang, S. H. Org.
Lett. 2018, 20, 4824. (i) Mao, R.-Z.; Balon, J.; Hu, X.-L. Angew. Chem.,
Int. Ed. 2018, 57, 13624. Xiang, J.-B.; Shang, M.; Kawamata, K.;
Lundberg, H.; Reisberg, S. H.; Chen, M.; Mykhailiuk, P.; Beutner, G.;
Collins, M. R.; Davies, A.; et al. Nature 2019, 573, 398. (j) Xue, W.;
Oestreich, M. Angew. Chem., Int. Ed. 2017, 56, 11649. (k) Jin, Y.;
Yang, H.-J.; Fu, H. Chem. Commun. 2016, 52, 12909. (l) Jiang, M.;
Yang, H.-J.; Fu, H. Org. Lett. 2016, 18, 1968. (m) Wang, D.; Zhu, N.;
Chen, P.; Lin, Z.; Liu, G. J. Am. Chem. Soc. 2017, 139, 15632−15635.
(n) Mao, R.; Balon, J.; Hu, X. Angew. Chem., Int. Ed. 2018, 57, 9501.
(10) (a) Zhang, X.-H.; Smith, R. T.; Le, C.; McCarver, S. J.;
Shireman, B. T.; Carruthers, N. I.; MacMillan, D. W. C. Nature 2020,
580, 220. (b) Kiyokawa, K.; Watanabe, T.; Fra, L.; Kojima, T.;
Minakata, S. J. Org. Chem. 2017, 82, 11711. (c) Sakakibara, Y.; Ito, E.;
Fukushima, T.; Murakami, K.; Itami, K. Chem. - Eur. J. 2018, 24,
9254. (d) Le Vaillant, F.; Courant, T.; Waser, J. Angew. Chem., Int. Ed.
2015, 54, 11200−11204. (e) Zhou, Q. Q.; Guo, W.; Ding, W.; Wu,
X.; Chen, X.; Lu, L. Q.; Xiao, W. J. Angew. Chem., Int. Ed. 2015, 54,
11196−11199.
(11) (a) Babu, K. R.; Zhu, N.-B; Bao, H. Org. Lett. 2017, 19, 46. Ye,
C.-Q; Qian, B.; Li, Y.-J; Su, M.; Li, D.-L; Bao, H. Org. Lett. 2018, 20,
3202. (b) Zhu, X.-T; Su, M.-Q.; Zhang, Q.; Li, Y.-J; Bao, H. Org. Lett.
2020, 22, 620. (c) Ye, C.-Q; Li, Y.-J; Bao, H. Adv. Synth. Catal. 2017,
359, 3720. (d) Jian, W.-J; Ge, L.; Jiao, Y.-H; Qian, B.; Bao, H. Angew.
Chem., Int. Ed. 2017, 56, 3650. (e) Zhu, N.-B; Zhao, J.-G; Bao, H.
Chem. Sci. 2017, 8, 2081. (f) Ye, C.-Q; Li, Y.-J; Zhu, X.-T; Hu, S.-M;
Yuan, D.-Q; Bao, H. Chem. Sci. 2019, 10, 3632. (g) Ge, L.; Li, Y.-J;
Jian, W.-J; Bao, H. Chem. - Eur. J. 2017, 23, 11767. (h) Zhu, X.-T;
Deng, W.-L; Chiou, M.-F; Ye, C.-Q; Jian, W.-J; Zeng, Y.-H; Jiao, Y.-
H; Ge, L.; Li, Y.-J; Zhang, X.-H; Bao, H. J. Am. Chem. Soc. 2019, 141,
548. (i) Wei, D.; Liu, T.; Zhou, B.; Han, B. Org. Lett. 2020, 22, 234.
Zhang, Y.; Feng, J.; Li, C.-J. J. Am. Chem. Soc. 2008, 130, 2900−2901.
(j) Dirocco, D. A.; Dykstra, K.; Krska, S.; Vachal, P.; Conway, D. V.;
Tudge, M. Angew. Chem., Int. Ed. 2014, 53, 4802−4806. (k) Li, Y.;
Han, Y.; Xiong, H.; Zhu, N.; Qian, B.; Ye, C.; Kantchev, E. A.; Bao, H.
Org. Lett. 2016, 18, 392−395. (l) Tian, H.; Xu, W.; Liu, Y.; Wang, Q.
Org. Lett. 2020, 22, 5005−5008.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank the Natural Science Foundation of China (nos.
21901100 and 21625203), the Jiangxi Province Science and
Technology Project (nos. 20202ACBL216017 and
20182BCB22007), and the Jiangxi Provincial Graduate
Innovation Special Fund (no. YC2019008) for financial
support.
REFERENCES
■
(1) (a) Ponnapalli, M. G.; Sura, M. B.; Sudhakar, R.; Govindarajalu,
G.; Sijwali, P. S. J. Agric. Food Chem. 2018, 66, 10490. (b) Zhang, N.;
Yu, Z. M.; Yang, X. H.; Hu, P.; He, Y. Eur. J. Med. Chem. 2018, 150,
829. (c) Jia, X.; Sheng, W. B.; Li, W.; Tong, Y. B.; Liu, Z. Y.; Zhou, F.
ACS Appl. Mater. Interfaces 2014, 6, 19552. (d) Lawrence, S. A.
Amines: Synthesis, Properties and Applications; Cambridge University
Press: Cambridge, U.K., 2004. (e) Vitaku, E.; Smith, D. T.;
Njardarson, J. T. J. Med. Chem. 2014, 57, 10257.
(2) (a) Urieta-Mora, J.; Garcia-Benito, I.; Molina-Ontoria, A.;
Martin, N. Chem. Soc. Rev. 2018, 47, 8541. (b) Liu, C.; Wang, X.-Q.;
Li, Z.-D.; Cui, L.; Li, C. J. Am. Chem. Soc. 2015, 137, 9820. (c) Luo, J.;
Wei, W.-T. Adv. Synth. Catal. 2018, 360, 2076. (d) Chen, J.-Y.; Wu,
W.; Li, Q.; Wei, W.-T. Adv. Synth. Catal. 2020, 362, 2770. (e) Shao,
X.-Q.; Zheng, Y.; Tian, L.-F.; Martín-Torres, I.; Echavarren, A. M.;
Wang, Y.-H. Org. Lett. 2019, 21, 9262. (f) Deng, G.; Chen, W.; Li, C.-
J. Adv. Synth. Catal. 2009, 351, 353−356. (g) Zheng, Y.; Narobe, R.;
̈
Donabauer, K.; Yakubov, S.; Konig, B. ACS Catal. 2020, 10, 8582.
(3) (a) Salvatore, R. N.; Yoon, C. H.; Jung, K. W. Tetrahedron 2001,
57, 7785−7811. (b) Swamy, K. C. K.; Kumar, N. N. B.; Balaraman,
E.; Kumar, K. V. P. P. Chem. Rev. 2009, 109, 2551−2651. (c) Le, Z.-
G.; Chen, Z.-C.; Hu, Y.; Zheng, Q.-G. Synthesis 2004, 208−212.
(d) Wang, X.-J.; Sidhu, K.; Zhang, L.; Campbell, S.; Haddad, N.;
Reeves, D. C.; Krishnamurthy, D.; Senanayake, C. H. Org. Lett. 2009,
11, 5490−5493. (e) Advanced Organic Chemistry: Part B: Reactions
and Synthesis, 5th ed.; Carey, F. A., Sundberg, R. J., Eds.; Springer
Science+Business Media, LLC, 2007; pp 229−232. (f) Gomez, S.;
Peters, J. A.; Maschmeyer, T. The Reductive Amination of Aldehydes
and Ketones and the Hydrogenation of Nitriles: Mechanistic Aspects
and Selectivity Control. Adv. Synth. Catal. 2002, 344, 1037−1057.
(g) Baxter, E. W.; Reitz, A. B. Org. React. 2002, 59, 1−714.
(h) Huang, L.; Arndt, M.; Gooßen, K.; Heydt, H.; Gooßen, L. J.
Chem. Rev. 2015, 115, 2596−2697. (i) Gui, J.; Pan, C.-M.; Jin, Y.;
Qin, T.; Lo, J. C.; Lee, B. J.; Spergel, S. H.; Mertzman, M. E.; Pitts, W.
J.; La Cruz, T. E.; Schmidt, M. A.; Darvatkar, N.; Natarajan, S. R.;
Baran, P. S. Science 2015, 348, 886−891. (j) Jiang, H.; Studer, A.
(12) For copper-catalyzed radical-mediated functionalization, see:
(a) Bao, X.; Wang, Q.; Zhu, J. Nat. Commun. 2019, 10, 769−775.
(b) Zhang, W.; Wang, F.; McCann, S.-D.; Wang, D.-H.; Chen, P.;
Stahl, S.-S.; Liu, G. Science 2016, 353, 1014−1018. (c) Budai, B.;
Leclair, A.; Wang, Q.; Zhu, J. Angew. Chem., Int. Ed. 2019, 58, 10305−
1003
https://dx.doi.org/10.1021/acs.orglett.0c04203
Org. Lett. 2021, 23, 1000−1004

Organic Letters
pubs.acs.org/OrgLett
Letter
10309. (d) ChatalovaSazepin, C.; Wang, Q.; Sammis, G. M.; Zhu, J.
Angew. Chem., Int. Ed. 2015, 54, 5443−5536. (e) Li, Z.; Wang, Q.;
Zhu, J. Angew. Chem., Int. Ed. 2018, 57, 13288−13292. (f) Su, X.-L.;
Ye, L.; Chen, J.-J.; Liu, X.-D.; Jiang, S.-P.; Wang, F.-L.; Liu, L.; Yang,
C.-J.; Chang, X.-Y.; Li, Z.-L.; Gu, Q.-S.; Liu, X.-Y. Angew. Chem., Int.
Ed. 2021, 60, 380−384. (g) Li, J.; Zhang, Z.; Wu, L.; Zhang, W.;
Chen, P.; Lin, Z.; Liu, G. Nature 2019, 574, 516−521. (h) Yang, C.-J.;
Zhang, C.; Gu, Q.-S.; Fang, J.-H.; Su, X.-L.; Ye, L.; Sun, Y.; Tian, Y.;
Li, Z.-L.; Liu, X.-Y. Nat. Catal. 2020, 3, 539−546. (i) Gephart III, R.
T.; Huang, D. L.; Aguila, M. J. B.; Schmidt, G.; Shahu, A.; Warren, T.
H. Angew. Chem., Int. Ed. 2012, 51, 6488−6492. (j) Jang, E. S.;
̈
McMullin, C. L.; Kaß, M.; Meyer, K.; Cundari, T. R.; Warren, T. H. J.
Am. Chem. Soc. 2014, 136, 10930−10940.
1004
https://dx.doi.org/10.1021/acs.orglett.0c04203
Org. Lett. 2021, 23, 1000−1004