C-H alkylation of heteroarenes with alkyl oxalates by molecular photoelectrocatalysis

Article abstract of DOI:10.1055/a-1296-8652

An oxidant- and metal-free photoelectrocatalytic C-H alkylation reaction of heteroarenes with alkyl oxalates has been developed. Several classes of heteroaromatics, such as quinolines, isoquinolines, pyridines, and phenanthridines, can be alkylated with t

Full text of DOI:10.1055/a-1296-8652

Submission Date:
Accepted Date:
Publication Date:
2020-09-23
2020-10-23
2020-10-23
Accepted Manuscript
Synlett
C-H Alkylation of Heteroarenes with Alkyl Oxalates by Molecular Photoelec-
trocatalysis
Fan Xu, Xiao-Li Lai, Hai-Chao Xu.
Affiliations below.
DOI: 10.1055/a-1296-8652
Please cite this article as: Xu F, Lai X-L, Xu H-C. C-H Alkylation of Heteroarenes with Alkyl Oxalates by Molecular Photoelectrocatalysis.
Synlett 2020. doi: 10.1055/a-1296-8652
Conflict of Interest: The authors declare that they have no conflict of interest.
This study was supported by National Natural Science Foundation of China (http://dx.doi.org/10.13039/501100001809), 21971213
Abstract:
An oxidant- and metal-free photoelectrocatalytic C–H alkylation reaction of heteroarenes with alkyl oxalates has been de-
veloped. Several classes of heteroaromatics such as quinoline, isoquinoline, pyridine, and phenanthridine are alkylated with
tertiary and secondary alkyl oxalates. The photoelectrochemical synthesis employs 4CzIPN as a molecular catalyst and allows
the oxidative transformations to proceed through H₂ evolution without need for sacrificial chemical oxidants.
Corresponding Author:
Hai-Chao Xu, Xiamen University, Chemistry, 422 SOUTH SIMING ROAD, 361005 Xiamen, China, haichao.xu@xmu.edu.cn
Affiliations:
Fan Xu, Xiamen University, Chemistry, Xiamen, China
Xiao-Li Lai, Xiamen University, Chemistry, Xiamen, China
Hai-Chao Xu, Xiamen University, Chemistry, Xiamen, China
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Synlett
Letter / Cluster / New Tools
C-H Alkylation of Heteroarenes with Alkyl Oxalates by Molecular
Photoelectrocatalysis
F. Xua
X.-L. Lai
a
a
H.-C. Xu*
a
Key Laboratory of Chemical Biology of Fujian Province, College
cat
of Chemistry and Chemical Engineering, Xiamen University,
4
22 South Siming Road, Xiamen 361005, China.
O
CO H
2
+
H
Het
R
Het
R
*
indicates the main/corresponding author.
+
H
O
2
CO2
2
Note: If an author has relocated from where the
research was carried out, this is indicated with the
next available reference number (usually 1); the new
address should be added as that reference in the
reference section.
and 3 alkyl (R)
2o
o
No metal catalyst
No external oxidant
20 examples
haichao.xu@xmu.edu.cn
Dedicated to Prof. Ilhyong Ryu on the occasion of his
th
7
0
birthday.
Received:
Accepted:
Published online:
DOI:
the advantages of both technologies, is emerging as a powerful
tool for the development of sustainable synthetic methods.5,6
Although research in this direction dates back in 1980s,7
Abstract An oxidant- and metal-free photoelectrocatalytic C–H alkylation
reaction of heteroarenes with alkyl oxalates has been developed. Several
classes of heteroaromatics such as quinoline, isoquinoline, pyridine, and
phenanthridine are alkylated with tertiary and secondary alkyl oxalates. The
photoelectrochemical synthesis employs 4CzIPN as a molecular catalyst and
synthetic applications of molecular photoelectrochemistry
8
9
remained unexplored until very recently by us and others. In
this context, we have reported photoelectrochemical alkylation
reactions of heteroarenes with organotrifluoroborates,
carboxylic acids or alkanes as alkylation agents (Scheme 1,
allows the oxidative transformations to proceed through H
2
evolution
without need for sacrificial chemical oxidants.
8
top). In these reactions, the alkylation agents are converted to
alkyl radicals, which undergo radical addition to the
heteroarenes to forge the key C–C bond.
Key words Synthetic photoelectrochemistry, molecular photoelectrocatalysis,
C-H functionalization, alkyl oxalates, heterocycles
our previous work
1
2
Organic electrochemistry and molecular photochemistry are
two promising synthetic tools that have been attracting
renewed interests. Electrochemistry, due to the ability of the
counter electrode to self-adjust its potential to achieve electron
flow, can often employs benign and abundant electron acceptors
or donors (such as protons or solvent molecules) to achieve
oxidation or reduction processes. As a result, electrochemical
dehydrogenative reactions do not require external electron and
R
BF K
3
R
R
CO
H
H
cat
2
Het
+
H
Het
R
O
CO H
2
R
O
this work
Scheme 1 Photoelectrochemical C-H alkylation of heteroarenes
proton acceptors and generate H
2
as the sole theoretical
byproduct. While both photoredox catalysis and organic
electrochemistry are powerful in promoting single electron
transfer (SET) processes, one relies on transient excited states,
the other uses electrodes as an electron reservoir or sink. These
differences allow the two technologies to achieve different
selectivities. For example, electron-rich alkyl radicals generated
through SET oxidation by an excited photocatalyst rarely
undergo further oxidation to carbocations because the transient
nature of the excited state catalyst and the radical species makes
additional SET between them difficult. On the other hand,
electron-rich carbon radicals generated electrochemically are
Alkyl oxalates, which are prepared from alcohols, have been
shown by Macmillan and Overman to be viable precursors for
alkyl radicals under visible light photoredox conditions.10 The
Overman group reported latter a C–H alkylation reaction of
heteroarenes with tertiary alkyl oxalates in the presence of a Ir-
based photocatalyst and a stoichiometric (NH
4
)
2
S
2
8
O as terminal
oxidant.11a The authors found that secondary oxalates were
much less efficient than tertiary ones probably due to slower
decarboxylation of the former.10 It has been suggested that
decarboxylative radical reactions of oxalates are difficult to
achieve under electrochemical conditions.12 We thus envision a
photoelectrochemical approach to achieve decarboxylative
cross coupling reactions of oxalates. We report herein metal-
and oxidant-free photoelectrocatalytic C-H alkylation reaction of
frequently oxidized further to carbocations due to their low
oxidation potentials.3,4
Molecular photoelectrochemistry, which combines the methods
of electrochemistry and molecular photochemistry and shares
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Synlett
Letter / Cluster / New Tools
heteroarenes with secondary and tertiary alkyl oxalates
employing an organic molecular catalyst (Scheme 1, bottom).
cat
O
COOH
Het
H
+
R
Het
R
O
4CzIPN (1 mol%)
0.2 equiv)
(
We chose the alkylation of lepidine (1) with secondary oxalate 2
as a model reaction for optimization of conditions.13 The
photoelectrocatalytic reaction was conducted with a constant
current of 2 mA in an undivided cell that was exposed to blue
LEDs (455 nm) and equipped with a reticulated vitreous carbon
4
Et NPF
6
TFA (1 equiv), MeCN
455 nm LEDs, 2 mA
Scope of Oxalates
R =
(
RVC) anode and Pt plate cathode. The solution contained MeCN
as solvent, 1,2,3,5-tetrakis(carbazol-9-yl)-4,6-dicyanobenzene
4CzIPN) as the catalyst,14 trifluoroacetic acid (TFA) as an
additive, and Et NPF as the supporting electrolyte. Under these
4, 75%
5, 71%
6, 70% (68%)[a] 7, 50%, >20:1 d.r.
N
R
(
4
6
, 71% (80%)[b]
9,
90%
10, 84%
11, 63%
8
conditions, the desired product 3 was obtained in an optimal
yield of 76%. Control experiments showed that the catalyst
Scope of Heteroarenes
CO
2
Me
(
(
entry 2), electricity (entry 3), light irradiation (entry 4), TFA
entry 5), and supporting electrolyte Et NPF (entry 6) were all
N
N
4
6
N
N
needed to obtain optimal results. Residual oxygen was probably
served as the terminal oxidant in the absence of electricity to
promote the formation of 3. The use of other salts such as
N
1
2, 78%
13, 80%
14, 77%
Et
materials such as Ni cathode (entry 9) or graphite anode (entry
0) resulted in inferior results.
4
NOTs (entry 7) or nBu
4
NPF
6
(entry 8) or other electrode
15, 60%[c]
Br
S
N
1
N
N
N
Table 1 Optimization of reaction conditions.[a]
16, 96%
17, 57%
18, 40%
19, 37%
cat
O
O
CO
2
H
N
N
+
NH
N
O
4CzIPN (1 mol%)
N
N
N
N
TFA, Et
55 nm LEDs, 2 mA
standard conditions"
4
NPF
6
, MeCN
4
N
1
2
3
"
6
7%[c]
(1 equiv)
(3 equiv)
20,
21, 45%
22, 18%
23, 0%
Entry
Deviation from standard conditions
Yield [%][b]
1
2
3
4
5
6
7
8
9
None
76[c]
Scheme
2 Reaction scope. [a] iPrCOCOOH as alkylation agent. [b]
No 4CzIPN
No electricity
No LEDs
No TFA
11 (74)
46 (43)
<5 (11)
37 (47)
60 (27)
55 (29)
32 (35)
10 (16)
11 (57)
tBuCOCOOH as alkylation agent. [a] Reaction with 6 equiv of oxalate.
RVC anode
Pt cathode
No Et
Et NOTs
nBu NPF
4
NPF
6
4
+
4
6
2H
-
Ni plate as cathode
graphite plate as anode
2e
N
10
I
H
[
a] Reaction conditions: 1 (0.2 mmol), 2 (0.6 mmol), 4CzIPN (0.002 mmol), TFA (0.2
mmol), Et NPF (0.04 mmol), MeCN (6 mL), RVC anode, Pt cathode, 2 mA, 11.5 h
mol 1). [b] Yield determined by H-NMR analysis using 1,3,5-
4.3
trimethoxybenzene as the internal standard. Unreacted was shown in
parenthesis. [c] Isolated yield.
R
= -
Ered
4CzIPN
1.21 V
H
4
6
−
1
2
(
F
1
H
hv
N
R
H
II
*
The scope of the photoelectrocatalytic C–H alkylation reaction
was explored (Scheme 2).15 Several secondary (3–7)16 and
4CzIPN
=
1.35 V
Ered
tertiary (8–11) oxalates reacted efficiently with lepidine to give
the desired alkylated products. Primary alkyl oxalates were
inefficient alkylation reagents under these conditions, although
ethyl oxalate reacted with phenanthridine in 40% yield (18).
Viable heteroaromatic scaffolds included 2-substituted
quinoline (12), isoquinoline (13, 14), phthalazine (15),
4CzIPN
N
H
R
R
SET
+ 2CO2
O
COO
III
-
R
2e
R
O
N
H
IV
phenanthridine
(16-18),
benzothiazole
(19),
1,10-
phenanthroline (20),17 and pyridine (21).18 While
quinazolinone (22) afforded low yield of the alkylation product,
quinoxaline (23) failed completely. Note that secondary and
tertiary a-keto acids are also viable alkylation agents under the
photoelectrochemical conditions as demonstrated for the
synthesis of compounds 6 and 8.
Scheme 3 Proposed mechanism
While alkyl oxalates are attractive radical precursors because of
the ease availability of alcohols, alkyl hydrogen oxalates,
particularly tertiary ones, undergo disproportionation to give
oxalic acid and dialkyl oxalates on storage and during the
photoelectrochemical reaction.10 Although the cesium oxalate
salts are more stable on storage and easy to handle, they are less
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Synlett
Letter / Cluster / New Tools
effective than the hydrogen oxalates for the present
photoelectrocatalytic alkylation reactions. In addition,
disproportionation cannot be avoided under the acidic
conditions, which are essential for the C–H alkylation of
heteroarenes. The stability issues associated with oxalates
hampered the further development of photoelectrocatalytic C–H
alkylation reactions with these agents.
Jiao, K.-J.; Xing, Y.-K.; Yang, Q.-L.; Qiu, H.; Mei, T.-S. Acc. Chem. Res.
2020, 53, 300. (p) Ackermann, L. Acc. Chem. Res. 2020, 53, 84.
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2
1
A
possible
mechanism
was
proposed
for
the
Reisberg, S. H.; Chen, M.; Mykhailiuk, P.; Beutner, G.; Collins, M. R.;
Davies, A.; Del Bel, M.; Gallego, G. M.; Spangler, J. E.; Starr, J.; Yang,
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Xu, F.; Long, H.; Song, J.; Xu, H.-C. Angew. Chem. Int. Ed. 2019, 58,
9017.
photoelectrocatalytic C–H alkylation reaction based on
literature reports10 and our previous work (Scheme 3). Single
8
ox
electron transfer (SET) oxidation of the alkyl oxalate (E
V vs SCE for tBuOCOCO
CZIPN* (Ered = 1.35 V vs SCE) generates persistent radical
p
= 1.28
Cs)10 by the photoexcited catalyst
2
4
−
•
(
4) Wayner, D. D. M.; McPhee, D. J.; Griller, D. J. Am. Chem. Soc. 1988,
anion 4CzIPN• and alkyl radical R after double decarboxylation.
1
10, 132.
5) (a) Barham, J. P.; Konig, B. Angew. Chem. Int. Ed. 2020, 59, 11732.
b) Yu, Y.; Guo, P.; Zhong, J.-S.; Yuan, Y.; Ye, K.-Y. Org. Chem. Front.
020, 7, 131. (c) Liu, J.; Lu, L.; Wood, D.; Lin, S. ACS Cent. Sci. 2020,
6, 1317.
•
Addition of R onto protonated heterocycle I generates radical
(
cation II, which undergoes highly exothermic SET reduction
with 4CzIPN• to afford 1,2-dihydroquinoline III with
concomitant regeneration of the ground state catalyst 4CzIPN
(
2
−
Ered = -1.21 V vs SCE). II (Ep/2 = 0.47 V vs SCE for R = nBu) is
ox
(6) Molecular photoelectrochemistry employs molecules dispersed in
the solution or attached to the electrode surface as light absorber
as opposed to interfacial photoelectrochemistry that uses
semiconductor photoelectrodes. For a recent review on the
synthetic applications of the latter, see: Wu, Y.-C.; Song, R.-J.; Li, J.-
H. Org. Chem. Front. 2020, 7, 1895.
(
then oxidized at the anode through electron and proton loss to
furnish the final alkylated heterocycle IV.8b Protons are reduced
at the cathode to generate hydrogen gas, obviating the need for
sacrificial electron and proton acceptors.
(
(
(
7) (a) Moutet, J. C.; Reverdy, G. J. Chem. Soc. Chem. Commun. 1982,
54. (b) Chiba, K.; Yamaguchi, Y.; Tada, M. Tetrahedron Lett. 1998,
9, 9035. (c) Scheffold, R.; Orlinski, R. J. Am. Chem. Soc. 1983, 105,
200.
8) (a) Yan, H.; Hou, Z.-W.; Xu, H.-C. Angew. Chem. Int. Ed. 2019, 58,
592. (b) Lai, X.-L.; Shu, X.-M.; Song, J.; Xu, H.-C. Angew. Chem. Int.
In summary, an oxidant- and metal-free C–H alkylation reaction
of heteroarenes with alkyl oxalates have been achieved by
molecular photoelectrocatalysis with an organocatalyst.
Secondary and tertiary hydrogen oxalates undergo successful
decarboxylative alkylation with several types of N-
6
3
7
4
heteroaromatics and proceed through H
2
evolution.
Ed. 2020, 59, 10626. (c) Xu, P.; Chen, P.-Y.; Xu, H.-C. Angew. Chem.
Int. Ed. 2020, 59, 14275.
9) (a) Wang, F.; Stahl, S. S. Angew. Chem. Int. Ed. 2019, 58, 6385. (b)
Huang, H.; Strater, Z. M.; Rauch, M.; Shee, J.; Sisto, T. J.; Nuckolls, C.;
Lambert, T. H. Angew. Chem. Int. Ed. 2019, 58, 13318. (c) Huang,
H.; Lambert, T. H. Angew. Chem. Int. Ed. 2020, 59, 658. (d) Huang,
H.; Strater, Z. M.; Lambert, T. H. J. Am. Chem. Soc. 2020, 142, 1698.
(e) Kim, H.; Kim, H.; Lambert, T. H.; Lin, S. J. Am. Chem. Soc. 2020,
Funding Information
Financial support of this research from NSFC (21971213) is
acknowledged.
Acknowledgment
142, 2087. (f) Qiu, Y.; Scheremetjew, A.; Finger, L. H.; Ackermann,
We thank the support of Fundamental Research Funds for the Central
Universities.
L. Chem. Eur. J. 2020, 26, 3241. (g) Zhang, W.; Carpenter, K. L.; Lin,
S. Angew. Chem. Int. Ed. 2020, 59, 409. (h) Cowper, N. G. W.;
Chernowsky, C. P.; Williams, O. P.; Wickens, Z. K. J. Am. Chem. Soc.
Supporting Information
2020, 142, 2093. (i) Niu, L.; Jiang, C.; Liang, Y.; Liu, D.; Bu, F.; Shi,
R.; Chen, H.; Dutta Chowdhury, A.; Lei, A. J. Am. Chem. Soc. 2020,
DOI: 10.1021/jacs.0c08437.
YES (this text will be updated with links prior to publication)
(
10) Nawrat, C. C.; Jamison, C. R.; Slutskyy, Y.; MacMillan, D. W. C.;
Overman, L. E. J. Am. Chem. Soc. 2015, 137, 11270.
11) (a) Pitre, S. P.; Muuronen, M.; Fishman, D. A.; Overman, L. E. ACS
Catal. 2019, 9, 3413. (b) Zhang, X.-Y.; Weng, W.-Z.; Liang, H.; Yang,
H.; Zhang, B. Org. Lett. 2018, 20, 4686.
Primary Data
(
NO (this text will be deleted prior to publication)
References and Notes
(12) Gao, Y.; Wu, Z.; Yu, L.; Wang, Y.; Pan, Y. Angew. Chem. Int. Ed. 2020,
(1) (a) Francke, R.; Little, R. D. Chem. Soc. Rev. 2014, 43, 2492. (b)
59, 10859.
Yan, M.; Kawamata, Y.; Baran, P. S. Chem. Rev. 2017, 117, 13230.
(13) For examples of electrochemical Minsci-type alkylation reactions,
see ref (12) and: (a) Dou, G.-Y.; Jiang, Y.-Y.; Xu, K.; Zeng, C.-C. Org.
Chem. Front. 2019, 6, 2392. (b) Wang, Q.-Q.; Xu, K.; Jiang, Y.-Y.;
Liu, Y.-G.; Sun, B.-G.; Zeng, C.-C. Org. Lett. 2017, 19, 5517. (c)
O'Brien, A. G.; Maruyama, A.; Inokuma, Y.; Fujita, M.; Baran, P. S.;
Blackmond, D. G. Angew. Chem. Int. Ed. 2014, 53, 11868. (d) Ding,
H.; Xu, K.; Zeng, C.-C. Journal of Catalysis 2020, 381, 38.
(
(
c) Horn, E. J.; Rosen, B. R.; Baran, P. S. ACS Cent. Sci. 2016, 2, 302.
d) Waldvogel, S. R.; Lips, S.; Selt, M.; Riehl, B.; Kampf, C. J. Chem.
Rev. 2018, 118, 6706. (e) Möhle, S.; Zirbes, M.; Rodrigo, E.;
Gieshoff, T.; Wiebe, A.; Waldvogel, S. R. Angew. Chem. Int. Ed.
2018, 57, 6018. (f) Yuan, Y.; Lei, A. Acc. Chem. Res. 2019, 52, 3309.
(g) Feng, R.; Smith, J. A.; Moeller, K. D. Acc. Chem. Res. 2017, 50,
2
3
346. (h) Yang, Q. L.; Fang, P.; Mei, T. S. Chin. J. Chem. 2018, 36,
38. (i) Jiang, Y.; Xu, K.; Zeng, C. Chem. Rev. 2018, 118, 4485. (j) Ye,
(14) Luo, J.; Zhang, J. ACS Catal. 2016, 6, 873.
(15) General procedure for the photoelectrochemical alkylation
reactions: A 10 mL Schlenk tube equipped with a magnetic stir
bar was charged with the heteroarene (0.2 mmol, 1.0 equiv),
oxalate (0.6 mmol, 3.0 equiv), 4CzIPN (0.002 mmol, 1 mol%),
Z.; Zhang, F. Chin. J. Chem. 2019, 37, 513. (k) Xiong, P.; Xu, H. C. Acc.
Chem. Res. 2019, 52, 3339. (l) Wang, H.; Gao, X.; Lv, Z.; Abdelilah,
T.; Lei, A. Chem. Rev. 2019, 119, 6769. (m) Siu, J. C.; Fu, N.; Lin, S.
Acc. Chem. Res. 2020, 53, 547. (n) Meyer, T. H.; Finger, L. H.;
Gandeepan, P.; Ackermann, L. Trends in Chemistry 2019, 1, 63. (o)
4 6
Et NPF (0.04 mmol, 0.2 equiv) and MeCN (6 mL). The Schlenk
tube was equipped with a reticulated vitreous carbon (100 PPI)
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anode (0.5 cm x 1.5 cm x 1.2 cm) and a platinum plate (1 cm x 1
7.46 (m, 1H), 7.18 (s, 1H), 2.90 (td, J = 12.1, 3.4 Hz, 1H), 2.69 (s,
3H), 2.08–2.01 (m, 2H), 1.95–1.88 (m, 2H), 1.84–1.78 (m, 1H),
1.70–1.61 (m, 2H), 1.53–1.44 (m, 2H), 1.40–1.33 (m, 1H). 13C NMR
(151 MHz, CDCl ) δ 166.6, 147.7, 144.4, 129.6, 129.0, 127.1, 125.5,
3
123.7, 120.4, 47.7, 32.9, 26.7, 26.2, 19.0.
cm) cathode. The reaction mixture was bubbled with argon for 15
min. TFA (0.2 mmol, 1 equiv) was added. 455 nm LEDs (20 W)
were placed 2 cm to the side of the reactor. The reaction was
carried out using a constant current of 2 mA at about 50 °C
1
(
internal temperature) until complete consumption of the
substrate (detected by TLC or 1H NMR). The reaction was
quenched with saturated NaHCO and the aqueous layer was
(17) Spectra data for compound 20: H NMR (500 MHz, CDCl
3
) δ 7.91
(s, 2H), 7.37 (s, 2H), 3.52 (hept, J = 6.9 Hz, 2H), 2.74 (s, 6H), 1.47
(d, J = 7.0 Hz, 12H). 13C NMR (126 MHz, CDCl
) δ 167.4, 145.4,
) δ 6.81
3
3
extracted with ethyl acetate (3 x 10 mL). The organic extracts
were combined and concentrated under reduced pressure. The
residue was chromatographed through silica gel eluting with
144.2, 126.7, 121.1, 121.0, 37.3, 23.0, 19.5.
1
(18) Spectra data for compound 21: H NMR (600 MHz, CDCl
3
(s, 2H), 2.51 (s, 6H), 2.43 (tt, J = 12.0, 4.8 Hz, 1H), 1.92–1.73 (m,
ethyl acetate/hexanes to give the desired product.
6H), 1.48–1.35 (m, 4H). 13C NMR (151 MHz, CDCl
3
) δ 157.6, 157.4,
1
(
16) Spectra data for compound 3: H NMR (600 MHz, CDCl
3
) δ 8.07 (d,
119.1, 44.0, 33.7, 26.8, 26.2, 24.6.
J = 8.3 Hz, 1H), 7.95 (d, J = 8.1 Hz, 1H), 7.74–7.65 (m, 1H), 7.57–
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Contents
Page
S2
1
2
3
4
5
6
. General Information
. General Procedure for the Photoelectrochemical Reactions
. Characterization Data
S2
S2
. Procedures for the Synthesis of Oxalates
. References
S7
S8
. NMR Spectra
S9

1
. General Information
Anhydrous MeCN were purchased from Aldrich and used directly. Et
4
NPF were
6
purchased from TCI and used directly. Flash column chromatography was performed
with silica gel (200–300 mesh) which was purchased from Adamas. NMR spectra were
1
recorded on Bruker AV-400, Bruker AV-500, and Bruker AV-600 instruments. H NMR
spectra are reported in parts per million (ppm) downfield relative to TMS (0.00 ppm)
1
3
and all C NMR spectra are reported in ppm relative to CDCl (77.2 ppm) unless stated
3
otherwise. The abbreviations used for explaining the multiplicities were as follows: s =
singlet, d = doublet, t = triplet, q = quartet, m = multiplet, br = broad. The electrodes
used for the preparative electrolysis were the same as those previously reported.
2
. General Procedure for the Electrophotocatalytic Reactions
A 10 mL Schlenk tube equipped with a magnetic stir bar was charged with the
heteroarene (0.2 mmol, 1.0 equiv), oxalate (0.6 mmol, 3.0 equiv), 4CzIPN (0.002 mmol,
1
mol%), Et
4
NPF (0.04 mmol, 0.2 equiv) and MeCN (6 mL). The Schlenk tube was
6
equipped with a reticulated vitreous carbon (100 PPI) anode (0.5 cm x 1.5 cm x 1.2 cm)
and a platinum plate (1 cm x 1 cm) cathode. The reaction mixture was bubbled with
argon for 15 min. TFA (0.2 mmol, 1 equiv) was added. 455 nm LEDs (20 W) were
placed 2 cm to the side of the reactor. The reaction was carried out using a constant
current of 2 mA at about 50 °C (internal temperature) until complete consumption of
1
the substrate (detected by TLC or H NMR). The reaction was quenched with saturated
NaHCO and the aqueous layer was extracted with ethyl acetate (3 x 10 mL). The
3
organic extracts were combined and concentrated under reduced pressure. The residue
was chromatographed through silica gel eluting with ethyl acetate/hexanes to give the
desired product.
3
. Characterization Data
S2

N
1
2
-Cyclohexyl-4-methylquinoline (3). Colorless oil; Yield = 76%; Electricity = 4.3 F
−
1 1
mol ; H NMR (600 MHz, CDCl
3
) δ 8.07 (d, J = 8.3 Hz, 1H), 7.95 (d, J = 8.1 Hz, 1H),
.74–7.65 (m, 1H), 7.57–7.46 (m, 1H), 7.18 (s, 1H), 2.90 (td, J = 12.1, 3.4 Hz, 1H),
.69 (s, 3H), 2.08–2.01 (m, 2H), 1.95–1.88 (m, 2H), 1.84–1.78 (m, 1H), 1.70–1.61 (m,
7
2
2
1
13
H), 1.53–1.44 (m, 2H), 1.40–1.33 (m, 1H). C NMR (151 MHz, CDCl ) δ 166.6,
3
47.7, 144.4, 129.6, 129.0, 127.1, 125.5, 123.7, 120.4, 47.7, 32.9, 26.7, 26.2, 19.0.
N
1
2
-Cyclopentyl-4-methylquinoline (4). Colorless oil; Yield = 75%; Electricity = 4.4 F
−
1 1
mol ; H NMR (600 MHz, CDCl
3
) δ 8.21 (d, J = 8.4 Hz, 1H), 8.00 (d, J = 8.2 Hz, 1H),
7
3
.76 (ddd, J = 8.4, 6.8, 1.4 Hz, 1H), 7.59 (ddd, J = 8.2, 6.8, 1.2 Hz, 1H), 7.28 (s, 1H),
1
3
.52 (p, J = 8.3 Hz, 1H), 2.76 (s, 3H), 2.46–2.20 (m, 2H), 2.05–1.67 (m, 6H). C NMR
(151 MHz, CDCl
3
) δ 165.7, 147.4, 145.0, 130.4, 127.6, 127.0, 126.5, 123.8, 120.6, 47.5,
3
4.0, 26.2, 19.3.
N
1
2
-Cyclobutyl-4-methylquinoline (5). Colorless oil; Yield = 71%; Electricity = 4.4 F
−
1 1
mol ; H NMR (600 MHz, CDCl
3
) δ 8.11 (d, J = 8.4 Hz, 1H), 7.97 (d, J = 8.1 Hz, 1H),
.70 (ddd, J = 8.3, 6.7, 1.4 Hz, 1H), 7.53 (ddd, J = 8.2, 6.7, 1.3 Hz, 1H), 7.24 (s, 1H),
.88 (p, J = 8.8 Hz, 1H), 2.72 (s, 3H), 2.47 (td, J = 9.0, 6.0 Hz, 4H), 2.20–2.11 (m, 1H),
7
3
2
1
1
3
.02–1.94 (m, 1H). C NMR (151 MHz, CDCl ) δ 164.9, 147.7, 144.3, 129.7, 129.1,
3
27.0, 125.5, 123.7, 120.4, 42.8, 28.4, 18.9, 18.5.
N
1
2
-Isopropyl-4-methylquinoline (6). Colorless oil; Yield = 70%; Electricity = 4.4 F
−
1 1
mol ; H NMR (600 MHz, CDCl
3
) δ 8.09 (d, J = 8.4 Hz, 1H), 7.97 (d, J = 8.3 Hz, 1H),
7
3
.70 (ddd, J = 8.4, 6.8, 1.4 Hz, 1H), 7.53 (ddd, J = 8.2, 6.8, 1.2 Hz, 1H), 7.21 (s, 1H),
1
3
.26 (hept, J = 6.9 Hz, 1H), 2.72 (s, 3H), 1.42 (s, 3H), 1.41 (s, 3H). C NMR (151 MHz,
CDCl
3
) δ 167.4, 147.3, 144.9, 129.4, 129.3, 127.1, 125.7, 123.7, 119.9, 37.2, 22.7, 19.0.
S3

N
1
2
-((2S,5R)-2-Isopropyl-5-methylcyclohexyl)-4-methylquinoline (7). Colorless oil;
−
1 1
Yield = 50%; Electricity = 4.2 F mol ; H NMR (500 MHz, CDCl
.2 Hz, 1H), 7.94 (dd, J = 8.3, 1.4 Hz, 1H), 7.65 (ddd, J = 8.4, 6.8, 1.4 Hz, 1H), 7.49
ddd, J = 8.2, 6.8, 1.3 Hz, 1H), 7.12 (s, 1H), 2.87 (td, J = 11.7, 3.5 Hz, 1H), 2.68 (s,
3
) δ 8.05 (dd, J = 8.5,
1
(
3H), 1.91–1.86 (m, 2H), 1.84–1.77 (m, 2H), 1.75–1.66 (m, 1H), 1.56 (ddd, J = 11.6,
6.0, 3.0 Hz, 1H), 1.39–1.33 (m, 1H), 1.29–1.23 (m, 1H), 1.10 (dd, J = 11.9, 3.3 Hz, 1H),
0.92–0.90 (m, 3H), 0.82 (d, J = 6.9 Hz, 3H), 0.74 (d, J = 6.9 Hz, 3H).
N
1
2
-(tert-Butyl)-4-methylquinoline (8). Colorless oil; Yield = 71%; Electricity = 4.1 F
−
1 1
mol ; H NMR (600 MHz, CDCl
3
) δ 8.09 (d, J = 8.4 Hz, 1H), 7.97 (d, J = 8.3 Hz, 1H),
1
3
7
.71–7.66 (m, 1H), 7.54–7.49 (m, 1H), 7.38 (s, 1H), 2.72 (s, 3H), 1.49 (s, 9H). C NMR
(151 MHz, CDCl
3
) δ 169.1, 147.4, 143.7, 130.1, 128.8, 126.7, 125.5, 123.5, 119.0, 38.1,
3
0.3, 19.1.
N
1
4
-Methyl-2-(tert-pentyl)quinoline (9). Colorless oil; Yield = 90%; Electricity = 4.5 F
−
1 1
mol ; H NMR (600 MHz, CDCl
Hz, 1H), 7.68 (ddd, J = 8.3, 6.8, 1.4 Hz, 1H), 7.52 (ddd, J = 8.2, 6.8, 1.3 Hz, 1H), 7.33
s, 1H), 2.71 (d, J = 1.0 Hz, 3H), 1.87 (q, J = 7.5 Hz, 2H), 1.46 (s, 6H), 0.77 (t, J = 7.5
3
) δ 8.10 (d, J = 8.3 Hz, 1H), 7.97 (dd, J = 8.3, 1.4
(
1
3
Hz, 3H). C NMR (151 MHz, CDCl
3
) δ 168.2, 147.5, 143.5, 130.1, 128.7, 126.6, 125.5,
1
23.5, 119.5, 41.3, 36.0, 27.5, 19.1, 9.4.
N
2
4
-Methyl-2-(1-methylcyclohexyl)quinoline (10). Colorless oil; Yield = 84%;
−
1 1
Electricity = 4.4 F mol ; H NMR (600 MHz, CDCl
3
) δ 8.05 (d, J = 8.4 Hz, 1H), 7.93
(dd, J = 8.3, 1.4 Hz, 1H), 7.64 (ddd, J = 8.3, 6.8, 1.4 Hz, 1H), 7.48 (ddd, J = 8.2, 6.8,
1
1
1
.3 Hz, 1H), 7.32 (s, 1H), 2.68 (s, 3H), 2.42–2.30 (m, 2H), 1.66–1.56 (m, 4H), 1.50–
1
3
.41 (m, 4H), 1.29 (s, 3H). C NMR (151 MHz, CDCl ) δ 168.3, 147.7, 143.6, 130.1,
3
28.7, 126.6, 125.4, 123.5, 119.5, 41.4, 37.3, 26.5, 23.1, 19.1.
S4

N
1
2
-((1s,3s)-Adamantan-1-yl)-4-methylquinoline (11). White solid; Yield: 63%;
−
1 1
Electricity = 4.2 F mol ; H NMR (600 MHz, CDCl
3
) δ 8.11 (d, J = 8.4 Hz, 1H), 7.97
(d, J = 8.3 Hz, 1H), 7.72–7.66 (m, 1H), 7.60–7.49 (m, 1H), 7.36 (s, 1H), 2.72 (s, 3H),
1
3
2
.22–2.12 (m, 9H), 1.96–1.83 (m, 6H). C NMR (151 MHz, CDCl ) δ 168.8, 147.6,
3
1
43.7, 130.1, 128.7, 126.8, 125.4, 123.5, 118.6, 41.9, 39.7, 37.0, 29.0, 19.1.
N
3
4
-Cyclohexyl-2-methylquinoline (12). Colorless oil; Yield = 78%; Electricity = 4.3 F
−
1 1
mol ; H NMR (600 MHz, CDCl
3
) δ 8.10–7.98 (m, 2H), 7.66 (ddd, J = 8.2, 6.8, 1.4
Hz, 1H), 7.50 (ddd, J = 8.3, 6.8, 1.3 Hz, 1H), 7.18 (s, 1H), 3.39–3.22 (m, 1H), 2.73 (s,
3
1
1
H), 2.05–1.99 (m, 2H), 1.97–1.91 (m, 2H), 1.90–1.83 (m, 1H), 1.56 (m, 4H), 1.41–
1
3
.30 (m, 1H). C NMR (151 MHz, CDCl ) δ 158.9, 153.4, 148.2, 129.6, 128.9, 125.4,
3
25.2, 122.9, 118.4, 38.9, 33.7, 27.0, 26.4, 25.6.
N
4
−1
1
-Cyclohexylisoquinoline (13). Colorless oil; Yield = 80%; Electricity = 4.3 F mol ;
1H NMR (600 MHz, CDCl
) δ 8.50 (d, J = 5.6 Hz, 1H), 8.24 (d, J = 8.5 Hz, 1H), 7.82
d, J = 8.1 Hz, 1H), 7.68–7.64 (m, 1H), 7.60 (ddd, J = 8.3, 6.7, 1.3 Hz, 1H), 7.49 (d, J
3
(
=
5.7 Hz, 1H), 3.58 (tt, J = 11.8, 3.4 Hz, 1H), 2.05–1.78 (m, 7H), 1.56 (qt, J = 13.0, 3.5
1
3
Hz, 2H), 1.42 (qt, J = 12.9, 3.6 Hz, 1H). C NMR (151 MHz, CDCl
3
) δ 165.8, 142.0,
1
36.5, 129.6, 127.6, 126.9, 126.4, 124.8, 119.0, 41.6, 32.7, 27.0, 26.4.
N
CO Me
2
5
Methyl 1-cyclohexylisoquinoline-3-carboxylate (14). Light yellow solid; Yield =
−
1 1
7
7%; Electricity = 4.4 F mol ; H NMR (600 MHz, CDCl
3
) δ 8.41 (s, 1H), 8.34–8.26
(m, 1H), 8.02–7.92 (m, 1H), 7.77–7.70 (m, 2H), 4.04 (s, 3H), 3.59 (tt, J = 11.3, 3.6 Hz,
1
3
1
H), 2.05–1.91 (m, 6H), 1.87–1.80 (m, 1H), 1.61–1.52 (m, 2H), 1.48–1.41 (m, 1H). C
NMR (151 MHz, CDCl
3
) δ 167.0, 166.3, 140.8, 136.1, 130.2, 129.2, 129.2, 127.9, 125.1,
S5

1
22.5, 52.8, 42.2, 32.4, 26.9, 26.2.
N
N
1
1
,4-Dicyclohexylphthalazine (15). Reaction under general procedure but with 6 equiv
−
1 1
of oxalates. Colorless oil; Yield = 60%; Electricity = 6.2 F mol ; H NMR (600 MHz,
CDCl ) δ 8.16 (dd, J = 6.3, 3.3 Hz, 2H), 7.84 (dd, J = 6.3, 3.3 Hz, 2H), 3.46 (tt, J = 11.6,
.5 Hz, 2H), 2.08–1.93 (m, 11H), 1.84–1.79 (m, 3H), 1.52 (qt, J = 12.8, 3.4 Hz, 4H),
3
3
1
1
1
3
.38 (qt, J = 12.9, 3.6 Hz, 2H). C NMR (151 MHz, CDCl ) δ 161.9, 131.2, 125.1,
3
24.3, 40.6, 32.5, 27.0, 26.4.
N
6
6
-Isopropylphenanthridine (16). Light yellow oil; Yield = 96%; Electricity = 4.3 F
−
1 1
mol ; H NMR (600 MHz, CDCl
3
) δ 8.68 (d, J = 8.3 Hz, 1H), 8.57 (d, J = 8.1 Hz, 1H),
8
2
.35 (d, J = 8.3 Hz, 1H), 8.19 (d, J = 8.1 Hz, 1H), 7.92–7.81 (m, 1H), 7.79–7.68 (m,
1
3
H), 7.66–7.61 (m, 1H), 4.03 (hept, J = 6.8 Hz, 1H), 1.56 (d, J = 6.8 Hz, 6H). C NMR
) δ 166.0, 143.9, 133.2, 130.1, 128.5, 127.2, 126.3, 125.8, 124.9,
(151 MHz, CDCl
3
1
23.5, 122.7, 121.9, 31.6, 22.1.
N
3
6
-Cyclohexylphenanthridine (17). Colorless oil; Yield = 57%; Electricity = 4.0 F
−
1 1
mol ; H NMR (600 MHz, CDCl
3
) δ 8.62 (d, J = 8.2 Hz, 1H), 8.51 (d, J = 8.1 Hz, 1H),
.29 (d, J = 8.3 Hz, 1H), 8.13 (d, J = 8.1 Hz, 1H), 7.81–7.75 (m, 1H), 7.72–7.63 (m,
H), 7.60–7.55 (m, 1H), 3.60 (tt, J = 11.4, 3.2 Hz, 1H), 2.13–2.03 (m, 2H), 2.00–1.88
8
2
1
3
(
m, 4H), 1.87–1.81 (m, 1H), 1.63–1.51 (m, 2H), 1.49–1.38 (m, 1H). C NMR (151
MHz, CDCl ) δ 165.4, 144.0, 133.1, 130.0, 130.0, 128.5, 127.2, 126.2, 125.7, 124.8,
23.5, 122.7, 121.9, 42.1, 32.4, 27.0, 26.5.
3
1
N
7
−1
6
-Ethylphenanthridine (18). Colorless oil; Yield = 40%; Electricity = 4.3 F mol ;
) δ 8.65 (d, J = 8.3 Hz, 1H), 8.55 (dd, J = 8.2, 1.3 Hz, 1H),
.27 (d, J = 8.2 Hz, 1H), 8.13 (dd, J = 8.2, 1.3 Hz, 1H), 7.84 (ddd, J = 8.3, 7.0, 1.3 Hz,
1H NMR (400 MHz, CDCl
3
8
S6

1
H), 7.71 (dddd, J = 8.3, 6.9, 5.3, 1.3 Hz, 2H), 7.62 (ddd, J = 8.3, 7.0, 1.4 Hz, 1H), 3.42
(
q, J = 7.6 Hz, 2H), 1.52 (t, J = 7.6 Hz, 3H). 13C NMR (126 MHz, CDCl
3
) δ 163.4,
1
1
43.9, 133.1, 130.5, 129.7, 128.7, 127.4, 126.5, 126.4, 125.2, 123.8, 122.7, 122.1, 29.5,
3.8.
Br
S
N
6
6
-Bromo-2-cyclohexylbenzo[d]thiazole (19). Colorless oil; Yield = 37%; Electricity
−
1 1
=
4.4 F mol ; H NMR (600 MHz, CDCl ) δ 7.97 (d, J = 1.9 Hz, 1H), 7.83 (d, J = 8.6
3
1
3
Hz, 1H), 7.54 (dd, J = 8.7, 1.9 Hz, 1H), 1.51 (s, 9H). C NMR (151 MHz, CDCl ) δ
3
1
82.6, 152.3, 136.8, 129.3, 124.1, 123.9, 118.1, 38.6, 30.8.
N
N
2
,9-Diisopropyl-4,7-dimethyl-1,10-phenanthroline (20). Reaction under general
procedure but with 6 equiv of oxalates. Light yellow solid; Yield = 67%; Electricity =
−
1 1
4
6
1
2
.3 F mol ; H NMR (500 MHz, CDCl
3
) δ 7.91 (s, 2H), 7.37 (s, 2H), 3.52 (hept, J =
1
3
.9 Hz, 2H), 2.74 (s, 6H), 1.47 (d, J = 7.0 Hz, 12H). C NMR (126 MHz, CDCl
3
) δ
−1
67.4, 145.4, 144.2, 126.7, 121.1, 121.0, 37.3, 23.0, 19.5. IR (neat, cm ): 2958, 2924,
+
867, 1549, 1455, 1089, 750. ESI HRMS m/z (M+H) calcd 293.2012, obsd 293.2007.
N
3
4
4
4
1
-Cyclohexyl-2,6-dimethylpyridine (21). Colorless oil; Yield = 45%; Electricity =
−1 1
.3 F mol ; H NMR (600 MHz, CDCl ) δ 6.81 (s, 2H), 2.51 (s, 6H), 2.43 (tt, J = 12.0,
3
1
3
.8 Hz, 1H), 1.92–1.73 (m, 6H), 1.48–1.35 (m, 4H). C NMR (151 MHz, CDCl ) δ
3
57.6, 157.4, 119.1, 44.0, 33.7, 26.8, 26.2, 24.6.
O
NH
N
3
2
-Cyclohexylquinazolin-4(3H)-one (22). Light yellow solid; Yield = 18%; Electricity
−
1 1
=
6.2 F mol ; H NMR (600 MHz, CDCl ) δ 11.01 (s, 1H), 8.28 (d, J = 8.0 Hz, 1H),
3
7
.79–7.74 (m, 1H), 7.73–7.69 (m, 1H), 7.47 (t, J = 7.5 Hz, 1H), 2.71 (tt, J = 12.2, 3.7
Hz, 1H), 2.12–2.02 (m, 2H), 1.98–1.89 (m, 2H), 1.84–1.78 (m, 1H), 1.76–1.68 (m, 2H),
13
1
1
4
.50–1.34 (m, 3H). C NMR (151 MHz, CDCl
26.5, 126.4, 121.0, 45.0, 30.7, 26.1, 25.8.
. Procedures for the Synthesis of Oxalates
3
) δ 163.9, 160.0, 149.6, 134.8, 127.5,
S7

To a solution of alcohol (1.0 equiv.) in DCM (0.1 M) was added oxalyl chloride (1.2
equiv.) at 0 °C under argon. The mixture was warmed to rt gradually and stirred
overnight. H
extraction with CHCl
organic phase was dried over Na
which was used without further purification.
2
O was added. The resulting mixture was stirred for 30 min at rt before
. The aqueous layer was washed with CHCl3. The combined
SO , filtered and concentrated to afford the oxalate,
3
2
4
5
. References
1
. Zhang, X.-Y.; Weng, W.-Z.; Liang, H.; Yang, H.; Zhang, B., Visible-Light-Initiated,
Photocatalyst-Free Decarboxylative Coupling of Carboxylic Acids with N-
Heterocycles. Org. Lett. 2018, 20, 4686.
2
. Garza-Sanchez, R. A.; Tlahuext-Aca, A.; Tavakoli, G.; Glorius, F., Visible Light-
Mediated Direct Decarboxylative C–H Functionalization of Heteroarenes. ACS Catal.
2
017, 7, 4057.
3
. Sutherland, D. R.; Veguillas, M.; Oates, C. L.; Lee, A.-L., Metal-, Photocatalyst-,
and Light-Free, Late-Stage C–H Alkylation of Heteroarenes and 1,4-Quinones Using
Carboxylic Acids. Org. Lett. 2018, 20, 6863.
4
. Klauck, F. J. R.; James, M. J.; Glorius, F., Deaminative Strategy for the Visible-
Light-Mediated Generation of Alkyl Radicals. Angew. Chem. Int. Ed. 2017, 56, 12336.
. Li, G.-X.; Hu, X.; He, G.; Chen, G., Photoredox-Mediated Minisci-type Alkylation
of N-Heteroarenes with Alkanes with High Methylene Selectivity. ACS Catal. 2018, 8,
1847.
. Yan, H.; Hou, Z.-W.; Xu, H.-C., Photoelectrochemical C−H Alkylation of
Heteroarenes with Organotrifluoroborates. Angew. Chem. Int. Ed. 2019, 58, 4592.
. Lu, S.; Gong, Y.; Zhou, D., Transition Metal-Free Oxidative Radical
5
1
6
7
Decarboxylation/Cyclization for the Construction of 6-Alkyl/Aryl Phenanthridines. J.
Org. Chem. 2015, 80, 9336.
S8

6
. NMR Spectra
7
7
6
6
5
5
4
4
3
3
2
2
1
1
5
0
-
500
000
500
000
500
000
500
000
500
000
500
000
500
000
00
1H NMR (600 MHz, CDCl3)
N
500
1
1.0 10.5 10.0 9.5
9.0
8.5
8.0
7.5
7.0
6.5
6.0
5.5
5.0
f1 (ppm)
4.5
4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0.0 -0.5 -1.0
6
6
5
5
4
4
3
3
2
2
1
1
5
0
-
50
00
50
00
50
00
50
00
50
00
50
00
0
13C NMR (151 MHz, CDCl3)
N
50
2
10
200
190
180
170
160
150
140
130
120
110
100
f1 (ppm)
90
80
70
60
50
40
30
20
10
0
-10
S9

8
8
7
7
6
6
5
5
4
4
3
3
2
2
1
1
5
0
-
500
000
500
000
500
000
500
000
500
000
500
000
500
000
500
000
00
1H NMR (600 MHz, CDCl3
)
N
500
1
1.0 10.5 10.0 9.5
9.0
8.5
8.0
7.5
7.0
6.5
6.0
5.5
5.0
f1 (ppm)
4.5
4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0.0 -0.5 -1.0
6
6
5
5
4
4
3
3
2
2
1
1
5
0
-
50
00
50
00
50
00
50
00
50
00
50
00
0
13C NMR (151 MHz, CDCl3)
N
50
2
10
200
190
180
170
160
150
140
130
120
110
100
f1 (ppm)
90
80
70
60
50
40
30
20
10
0
-10
S10

6
5
5
4
4
3
3
2
2
1
1
5
0
-
000
500
000
500
000
500
000
500
000
500
000
00
1H NMR (600 MHz, CDCl3)
N
500
1
1.0 10.5 10.0 9.5
9.0
8.5
8.0
7.5
7.0
6.5
6.0
5.5
5.0
f1 (ppm)
4.5
4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0.0 -0.5 -1.0
400
1
3
C NMR (151 MHz, CDCl3)
350
300
250
200
150
100
50
0
N
2
10
200
190
180
170
160
150
140
130
120
110
100
f1 (ppm)
90
80
70
60
50
40
30
20
10
0
-10
S11

8
7
7
6
6
5
5
4
4
3
3
2
2
1
1
5
0
-
000
500
000
500
000
500
000
500
000
500
000
500
000
500
000
00
1H NMR (600 MHz, CDCl3
)
N
500
1
1.0 10.5 10.0 9.5
9.0
8.5
8.0
7.5
7.0
6.5
6.0
5.5
5.0
f1 (ppm)
4.5
4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0.0 -0.5 -1.0
1
300
200
1
13C NMR (151 MHz, CDCl3)
1100
1
9
8
7
6
5
4
3
2
1
0
-
000
00
00
00
00
00
00
00
00
00
N
100
2
10
200
190
180
170
160
150
140
130
120
110
100
f1 (ppm)
90
80
70
60
50
40
30
20
10
0
-10
S12

1
1
1
1
1
1
9
8
7
6
5
4
3
2
1
0
-
5000
4000
3000
2000
1000
0000
000
1H NMR (500 MHz, CDCl
3
)
N
000
000
000
000
000
000
000
000
1000
1
1.5 11.0 10.5 10.0 9.5
9.0
8.5
8.0
7.5
7.0
6.5
6.0
5.5
5.0
f1 (ppm)
4.5
4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0.0 -0.5 -1.0 -1.5
1
1
9
8
7
6
5
4
3
2
1
0
-
1000
0000
000
000
000
000
000
000
000
000
000
1H NMR (600 MHz, CDCl3
)
N
1000
1
1.0 10.5 10.0 9.5
9.0
8.5
8.0
7.5
7.0
6.5
6.0
5.5
5.0
f1 (ppm)
4.5
4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0.0 -0.5 -1.0
S13

6
6
5
5
4
4
3
3
2
2
1
1
5
0
-
50
00
50
00
50
00
50
00
50
00
50
00
0
13C NMR (151 MHz, CDCl3)
N
50
2
10
200
190
180
170
160
150
140
130
120
110
100
f1 (ppm)
90
80
70
60
50
40
30
20
10
0
-10
7000
6500
6000
5500
1H NMR (600 MHz, CDCl3)
N
5000
4
4
3
3
2
2
1
1
5
0
-
500
000
500
000
500
000
500
000
00
500
1
1.0 10.5 10.0 9.5
9.0
8.5
8.0
7.5
7.0
6.5
6.0
5.5
5.0
f1 (ppm)
4.5
4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0.0 -0.5 -1.0
S14

3
3
2
2
2
2
2
1
1
1
1
1
8
6
4
2
0
-
20
00
80
60
40
20
00
80
60
40
20
00
0
13C NMR (151 MHz, CDCl3)
N
0
0
0
20
2
10
200
190
180
170
160
150
140
130
120
110
100
f1 (ppm)
90
80
70
60
50
40
30
20
10
0
-10
5500
5000
4500
4000
3500
3000
2500
2000
1500
1000
500
0
1H NMR (600 MHz, CDCl3)
N
1
1.0 10.5 10.0 9.5
9.0
8.5
8.0
7.5
7.0
6.5
6.0
5.5
5.0
f1 (ppm)
4.5
4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0.0 -0.5 -1.0
S15

2
2
2
2
40
30
20
10
13
C NMR (151 MHz, CDCl3)
200
1
1
1
90
80
70
N
160
1
1
1
1
1
1
9
8
7
6
5
4
3
2
1
0
-
-
50
40
30
20
10
00
0
0
0
0
0
0
0
0
0
10
20
2
10
200
190
180
170
160
150
140
130
120
110
100
f1 (ppm)
90
80
70
60
50
40
30
20
10
0
-10
7
6
6
5
5
4
4
3
3
2
2
1
1
5
0
-
000
500
000
500
000
500
000
500
000
500
000
500
000
00
1H NMR (600 MHz, CDCl3)
N
500
1
1.0 10.5 10.0 9.5
9.0
8.5
8.0
7.5
7.0
6.5
6.0
5.5
5.0
f1 (ppm)
4.5
4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0.0 -0.5 -1.0
S16

8
7
00
50
13C NMR (151 MHz, CDCl3)
700
6
6
50
00
N
550
5
4
4
3
3
2
2
1
1
5
0
-
00
50
00
50
00
50
00
50
00
0
50
2
10
200
190
180
170
160
150
140
130
120
110
100
f1 (ppm)
90
80
70
60
50
40
30
20
10
0
-10
1
1
9
8
7
6
5
4
3
2
1
0
-
1000
0000
000
000
000
000
000
000
000
000
000
1H NMR (600 MHz, CDCl3)
N
1000
1
1.0 10.5 10.0 9.5
9.0
8.5
8.0
7.5
7.0
6.5
6.0
5.5
5.0
f1 (ppm)
4.5
4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0.0 -0.5 -1.0
S17

3
3
3
2
2
2
2
2
1
1
1
1
1
8
6
4
2
0
-
40
20
00
80
60
40
20
00
80
60
40
20
00
0
13C NMR (151 MHz, CDCl3)
N
0
0
0
20
2
10
200
190
180
170
160
150
140
130
120
110
100
f1 (ppm)
90
80
70
60
50
40
30
20
10
0
-10
6
5
5
4
4
3
3
2
2
1
1
5
0
-
000
500
000
500
000
500
000
500
000
500
000
00
1H NMR (600 MHz, CDCl3)
N
500
1
1.0 10.5 10.0 9.5
9.0
8.5
8.0
7.5
7.0
6.5
6.0
5.5
5.0
f1 (ppm)
4.5
4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0.0 -0.5 -1.0
S18

2
2
2
2
1
1
1
1
1
8
6
4
2
0
-
60
40
20
00
80
60
40
20
00
0
13C NMR (151 MHz, CDCl3)
N
0
0
0
20
2
10
200
190
180
170
160
150
140
130
120
110
100
f1 (ppm)
90
80
70
60
50
40
30
20
10
0
-10
2
2
2
2
2
1
1
1
1
1
8
6
4
2
0
-
800
600
400
200
000
800
600
400
200
000
00
1H NMR (600 MHz, CDCl3
)
CO Me
2
N
00
00
00
200
1
1.0 10.5 10.0 9.5
9.0
8.5
8.0
7.5
7.0
6.5
6.0
5.5
5.0
f1 (ppm)
4.5
4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0.0 -0.5 -1.0
S19

1
1
200
100
13C NMR (151 MHz, CDCl3)
1000
CO Me
2
9
8
7
6
5
4
3
2
1
0
-
00
00
00
00
00
00
00
00
00
N
100
2
10
200
190
180
170
160
150
140
130
120
110
100
f1 (ppm)
90
80
70
60
50
40
30
20
10
0
-10
5000
1H NMR (600 MHz, CDCl3)
4500
4000
3500
3000
2500
2000
1500
1000
500
0
N
N
1
1.0 10.5 10.0 9.5
9.0
8.5
8.0
7.5
7.0
6.5
6.0
5.5
5.0
f1 (ppm)
4.5
4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0.0 -0.5 -1.0
S20

4
4
3
3
2
2
1
1
5
0
-
50
00
50
00
50
00
50
00
0
13C NMR (151 MHz, CDCl3)
N
N
50
2
10
200
190
180
170
160
150
140
130
120
110
100
f1 (ppm)
90
80
70
60
50
40
30
20
10
0
-10
4000
1H NMR (600 MHz, CDCl3)
3800
3600
3400
3200
N
3000
2
2
2
2
2
1
1
1
1
1
8
6
4
2
0
-
800
600
400
200
000
800
600
400
200
000
00
00
00
00
200
1
1.0 10.5 10.0 9.5
9.0
8.5
8.0
7.5
7.0
6.5
6.0
5.5
5.0
f1 (ppm)
4.5
4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0.0 -0.5 -1.0
S21

7
6
00
50
1
3
C NMR (151 MHz, CDCl3)
600
5
5
4
4
3
3
2
2
1
1
5
0
-
50
00
50
00
50
00
50
00
50
00
0
N
50
2
10
200
190
180
170
160
150
140
130
120
110
100
f1 (ppm)
90
80
70
60
50
40
30
20
10
0
-10
4500
4000
3500
3000
2500
2000
1500
1000
500
0
1H NMR (600 MHz, CDCl3)
N
1
1.0 10.5 10.0 9.5
9.0
8.5
8.0
7.5
7.0
6.5
6.0
5.5
5.0
f1 (ppm)
4.5
4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0.0 -0.5 -1.0
S22

6
6
5
5
4
50
00
50
00
50
13C NMR (151 MHz, CDCl3)
N
400
3
3
2
2
1
1
5
0
-
50
00
50
00
50
00
0
50
2
10
200
190
180
170
160
150
140
130
120
110
100
f1 (ppm)
90
80
70
60
50
40
30
20
10
0
-10
1
1
1
1
1
1
1
1
9
8
7
6
5
4
3
2
1
0
-
700
600
500
400
300
200
100
000
00
1H NMR (400 MHz, CDCl3)
N
00
00
00
00
00
00
00
00
100
1
1.0 10.5 10.0 9.5
9.0
8.5
8.0
7.5
7.0
6.5
6.0
5.5
5.0
f1 (ppm)
4.5
4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0.0 -0.5 -1.0
S23

1
9
00000
0000
13C NMR (126 MHz, CDCl3)
80000
7
6
5
4
3
2
1
0
-
0000
0000
0000
0000
0000
0000
0000
N
10000
2
10
200
190
180
170
160
150
140
130
120
110
100
f1 (ppm)
90
80
70
60
50
40
30
20
10
0
-10
6
5
000
500
1H NMR (600 MHz, CDCl3
)
5000
Br
S
4
4
3
3
2
2
1
1
5
0
-
500
000
500
000
500
000
500
000
00
N
500
1
1.0 10.5 10.0 9.5
9.0
8.5
8.0
7.5
7.0
6.5
6.0
5.5
5.0
f1 (ppm)
4.5
4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0.0 -0.5 -1.0
S24

1
1
100
000
13C NMR (151 MHz, CDCl3)
Br
S
900
800
N
7
6
5
4
3
2
1
0
-
00
00
00
00
00
00
00
100
2
10
200
190
180
170
160
150
140
130
120
110
100
f1 (ppm)
90
80
70
60
50
40
30
20
10
0
-10
7
6
6
5
5
4
4
3
3
2
2
1
1
5
0
-
0000
5000
0000
5000
0000
5000
0000
5000
0000
5000
0000
5000
0000
000
1H NMR (500 MHz, CDCl3)
N
N
5000
1
1.0 10.5 10.0 9.5
9.0
8.5
8.0
7.5
7.0
6.5
6.0
5.5
5.0
f1 (ppm)
4.5
4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0.0 -0.5 -1.0
S25