Copper-Catalyzed Remote C?H Functionalization of 8-Aminoquinolines with Sodium and Lithium Sulfinates

Article abstract of DOI:10.1002/adsc.201600388

A simple and mild copper-catalyzed sulfonylation of 8-aminoquinolines with sodium and lithium sulfinates is reported. In the presence of manganese(III) acetate [Mn(OAc)₃] as cooxidant a highly site-selective C?H functionalization at the C-5 position takes place. The reaction proceeds readily at room temperature in air and various sulfones were synthesized in moderate to high yields. Moreover, a straightforward procedure for the conversion of organolithium reagents and sulfur dioxide into C-5 sulfonylated quinolines was developed. (Figure presented.).

Full text of DOI:10.1002/adsc.201600388

COMMUNICATIONS
DOI: 10.1002/adsc.201600388
ꢀ
Copper-Catalyzed Remote C H Functionalization of 8-Amino-
quinolines with Sodium and Lithium Sulfinates
a
a,
Shuai Liang and Georg Manolikakes *
a
Department of Organic Chemistry and Chemical Biology, Goethe University Frankfurt, Max-von-Laue-Straße 7, D-60438
Frankfurt am Main, Germany
E-mail: g.manolikakes@chemie.uni-frankfurt.de
Received: April 12, 2016; Revised: May 25, 2016; Published online: && &&, 0000
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201600388.
Abstract: A simple and mild copper-catalyzed sul-
fonylation of 8-aminoquinolines with sodium and
lithium sulfinates is reported. In the presence of
these processes rely extensively on prefunctionalized
starting materials. In this context, the direct function-
alization of CꢀH bonds offers an economically and
[
8]
manganese(III) acetate [Mn(OAc) ] as cooxidant
ecologically attractive alternative. In the last five
years, considerable effort has been devoted to the de-
velopment of new approaches for the synthesis of sul-
fones via selective functionalization of CꢀH bonds.
3
a highly site-selective CꢀH functionalization at the
C-5 position takes place. The reaction proceeds
readily at room temperature in air and various sul-
fones were synthesized in moderate to high yields.
Moreover, a straightforward procedure for the con-
version of organolithium reagents and sulfur diox-
ide into C-5 sulfonylated quinolines was developed.
Since the first report from Dong and co-workers on
the palladium-catalyzed sulfonylation of phenylpyri-
[
9a]
AHCTUNGTRENNUGNd ines, various metal-catalyzed and metal-free pro-
cedures for the direct sulfonylation of CꢀH bonds
[
9]
have been described. Recently, Tan and Shi as well
as our group have reported copper-mediated or
Keywords: CꢀH activation; copper; manganese;
2
sulfinates; sulfones; sulfonylation
copper-catalyzed C(sp )ꢀH sulfonylations of benzoic
acid derivatives with sulfinic acid salts employing dif-
[10]
ferent removable directing groups (Scheme 1a). Re-
gioselective sulfonylation in an ortho-position of the
directing group is observed in all three cases. Interest-
Sulfones are important building blocks in organic syn- ingly the copper-catalyzed sulfonylation of benzoic
[
11]
thesis and common structural motifs found in numer- acids bearing the 8-aminoquinoline auxiliary
with
ous pharmaceuticals, agrochemicals and functional sulfonyl chlorides does not occur at the phenyl ring.
[1]
materials. Among them, heteroaromatic sulfones Instead a remote C-5ꢀH sulfonylation of the quino-
have attracted particular interest as lead structures line ring takes place (Scheme 1b). Herein, we
for the development of potential drugs against various report a copper-catalyzed remote CꢀH sulfonylation
diseases, such as HIV or neurological disorders. of 8-aminoquinolines with sodium and lithium sulfi-
Traditional approaches for the synthesis of sulfones nates, which proceeds readily at room temperature.
include the oxidation of sulfides, the alkylation of sul- During our initial studies on the copper-mediated
finates, Friedel–Crafts-type sulfonylation of arenes sulfonylation of C(sp )ꢀH bonds with sulfinates
with sulfonyl chlorides or addition reactions of sulfo- made an interesting observation. Reaction of benzoic
[
12,13]
[
2]
[3]
2
[10c]
we
[
1,4]
nyl-based radicals to olefins and alkynes.
Often acid derivative 1a, bearing an 8-aminoquinoline auxil-
these classical methods are limited by their harsh re- iary, with sodium para-toluenesulfinate (2a) in the
action conditions or inherent reactivities governed by presence of 3 equivalents of Cu(OAc) in hexafluoro-
2
electronic effects of the starting materials. During the
ACHTUNGTRENNUNG
[
5]
[6]
free coupling reactions of sodium sulfinates have curred at the aminoquinoline ring, furnishing the C-5
been developed as milder, regioselective alternatives. and the C-7 substituted products 3a and 3aa in 42%
Extension of these procedures to in situ generated and 11% yields within 90 min at room temperature
metal sulfinates has led to the development of effi- (Table 1, entry 1). This result is in stark contrast to
[
10a]
cient multicomponent, one-pot sequences for the syn- the previous report by Tan,
which showed that re-
[
7]
thesis of sulfones. Although quite straightforward, gioselective ortho-sulfonylation occurs under basic
Adv. Synth. Catal. 0000, 000, 0 – 0
1
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÞÞ
These are not the final page numbers!

COMMUNICATIONS
asc.wiley-vch.de
conditions (Scheme 1). So far selective sulfonylation
of the 8-aminoquinoline motif is only possible using
[12]
harsh reaction conditions and high temperatures.
The novel reactivity, discovered during our initial
work, could provide a milder approach to C-5 sulfo-
nylated quinolines. In addition, this transformation
represents an unusual, condition-dependent switch in
the regioselectivity of copper(II)-mediated CꢀH func-
tionalizations, which warrants further examination.
Therefore we decided to investigate this transforma-
tion in more detail.
We started our studies with the optimization of the
reaction conditions (Table 1). After screening a range
of copper(II) salts, cooxidants, solvents and additives,
we could identify the optimal conditions. Best yields
were obtained with 20 mol% of CuCl , stoichiometric
2
amounts of Mn(OAc) (used as dihydrate) as cooxi-
3
dant in HFIP as solvent (entry 2). Other oxidizing
agents, such as PhI(OAc) or tert-butyl hydroperoxide
2
(
TBHP), did not lead to the formation of the desired
sulfonylated products (entries 3 and 4). Interestingly,
Scheme 1. Directed vs. remote CꢀH sulfonylation of 8-ami- Mn(OAc) alone can promote the CꢀH functionaliza-
3
[
14,15]
noquinoline.
tion, albeit in lower yields (entry 5).
Performing
the reaction in trifluoroethanol furnished the products
a and 3aa in a similar overall yield (85% vs. 94%),
however with a diminished regioselectivity (1.7:1 vs.
.5:1) (entry 6). Other solvents, including non-fluori-
3
[a]
Table 1. Optimization of the reaction conditions.
4
nated alcohols or acetonitrile, did not prove as effec-
tive as HFIP (entries 7 and 8). Decreasing the
amount of catalyst, sulfinate or Mn(OAc) led to a sig-
3
nificantly reduced yield (entries 9–11).
With the optimized conditions at hand, we explored
the substrate scope in terms of the sodium sulfinate
(
Table 2). In general, both electron-rich or electron-
poor arylsulfinic acid salts were well tolerated and the
desired C-5 sulfonylated products could be obtained
in good to excellent yields (3a–3i). In most cases the
minor C-7 regioisomer was formed only in trace
amounts or could not be detected at all. Only in the
case of 3e could the side product be isolated in 15%
yield. Reactions with heterocyclic sulfinates, such as
sodium pyridine-2-sulfinate, did not afford the desired
sulfones (3j). Treatment of 1a with sodium methylsul-
finate (2k) furnished the corresponding alkyl sulfone
[bj
Entry Catalyst
Oxidant
–
Mn(OAc)3 HFIP
TBHP HFIP
PhI(OAc)2 HFIP
Mn(OAc)3 HFIP
Mn(OAc)3 TFE
Mn(OAc)3 i-PrOH 26
Mn(OAc)3 CH CN <5
Mn(OAc)3 HFIP
Mn(OAc)3 HFIP
Mn(OAc)3 HFIP
Solvent Yield [%]
3a+3aa)
(
[
c]
1
2
3
4
5
6
7
8
9
1
1
Cu(OAc)2
CuCl2
HFIP
42+11
77+17
–
CuCl2
CuCl2
–
–
27+10
54+31
CuCl2
CuCl2
CuCl2
CuCl2
CuCl2
CuCl2
3
k in 58% yield. In this case a larger excess of the
alkyl sulfinate was necessary to achieve a good yield.
Subsequently, we investigated the effect of structur-
al variations in the 8-aminoquinoline on the C-5 sulfo-
nylation (Table 3). Reactions with substituted benz-
3
[
d]
56+20
51+10
53+14
[
[
e]
0
1
f]
AHCTUNGTRENNUGNa mides bearing electron-withdrawing or electron-do-
[
a]
Reactions conditions: 1a (0.2 mmol), 2a (3.0 equiv.,
nating substituents in the para-position as well as with
heterocyclic amides proceeded smoothly, affording
the diaryl sulfones 3l–3n and 3q in 73–96% yield. As
before, the C-7 regioisomer was observed only in
small amounts (<3%). Treatment of an acetamide-
protected 8-aminoquinoline with 4-chlorophenylsulfi-
nate furnished the desired product 3o in 91% yield.
0
.6 mmol), catalyst (20 mol%), oxidant (3.0 equiv.,
0
.6 mmol), solvent (2 mL), 258C, 90 min.
[
[
[
[
[
b]
Isolated yield.
c]
d]
e]
f]
3.0 equiv. Cu(OAc)2.
With 1.5 equiv. of Mn(OAc) ·2H O.
3
2
With 1.5 equiv. of 2a.
With 5 mol% CuCl2.
Adv. Synth. Catal. 0000, 000, 0 – 0
2
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÞÞ
These are not the final page numbers!

COMMUNICATIONS
asc.wiley-vch.de
[a]
[a]
Table 2. Substrate scope of sodium sulfinates.
Table 3. Substrate scope of sodium sulfinates.
[
[
a]
b]
Reactions conditions: 1a (0.2 mmol),
.6 mmol), CuCl2 (20 mol%), Mn(OAc) ·2H O
3.0 equiv., 0.6 mmol), HFIP (2 mL), 258C, 90 min.
With 5.0 equiv. sulfinate.
2 (3.0 equiv.,
0
(
3
2
[
[
a]
b]
Reactions conditions:
.6 mmol), CuCl2
(3.0 equiv., 0.6 mmol), HFIP (2 mL), 258C, 90 min.
Reaction performed at 808C for 20 h.
1
(0.2 mmol),
2
(3.0 equiv.,
0
(20 mol%), Mn(OAc) ·2H O
3
2
The method is somewhat sensitive to steric hindrance.
Reaction of an 8-aminoquinoline bearing a sterically
demanding pivaloyl amide required higher tempera-
tures and longer reaction times and sulfone 3p was
[
1]
isolated in only 25% yield. Structural modifications with sulfur dioxide, are an attractive alternative to
on the 8-aminoquinoline core are also possible to sodium sulfinates. Due to the broad availability of
[
7]
[
16]
a certain extent. Substituents in the 2- or 6-position organolithium reagents a wide range of these lithi-
are tolerated and the desired products 3s and 3t were um salts can be accessed. Therefore, both lithium
obtained in 41% and 89%. In the case of a quinoxa- phenyl- and n-butylsulfinates 5a and 5b were pre-
line-based starting material the heteroaryl sulfone is pared in nearly quantitative yields from the corre-
obtained in only 22% yield. Interestingly, no reaction, sponding lithium reagents and sulfur dioxide
even no C-7 functionalization, is observed with 8-ami- (Scheme 2). To our delight, lithium sulfinates are
noquinolines bearing already a substituent in the 5- compatible with our copper-catalyzed remote sulfony-
position, such as the chloro-derivative 1k.
lation and the reaction with aminoquinoline 1a af-
To increase the scope and applicability of our reac- forded the desired sulfones 3e and 3u in 85% and
tions, we next investigated a possible incorporation of 53% yields.
lithium sulfinates. Sulfinic acid lithium salts, easily
For further applications of our transformation in
prepared from the reaction of organolithium reagents the synthesis of complex sulfones, we explored the
Adv. Synth. Catal. 0000, 000, 0 – 0
3
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÞÞ
These are not the final page numbers!

COMMUNICATIONS
asc.wiley-vch.de
Scheme 2. Synthesis of sulfones starting from organolithium
reagents.
possible merger of our method with common proce-
dures for the generation of organolithium compounds.
To our delight, the two most common methods used
for the preparation of complex organolithium re-
agents, lithium–halogen exchange and deprotona-
Scheme 4. Unsuccessful starting materials for the copper-
catalyzed sulfonylation.
[16]
tion, are compatible with our copper-catalyzed Cꢀ
H-sulfonylation. Lithium para-toluenesulfinate (5c)
was synthesized in 72% yield starting from 4-iodoto- lated products under the standard conditions
luene (6) via lithium–iodine exchange with n-Buli fol- (Scheme 4a). In a similar manner reaction of the
lowed by reaction of the corresponding lithium re- more electron-rich naphthalene derivative 9, also not
agent with sulfur dioxide (Scheme 3a). Copper-cata- capable of bidentate coordination to metal centers,
lyzed coupling of sulfinate 5c with 8-aminoquinoline did not furnish any product at all (Scheme 4b). These
derivative 1a under standard conditions afforded the results rule out a pathway via electrophilic aromatic
desired C-5 sulfonylated product 3a in 92% yield. De- substitution and indicate that a chelation complex be-
protonation of anisole (7) and subsequent trapping tween both nitrogens of the 8-aminoquinoline and
with sulfur dioxide gave ortho-methoxyphenylsulfi- copper might be crucial for the CꢀH sulfonylation. In-
nate (5d) in 63% yield. Reaction of sulfinate 5d with terestingly, an acyl group on the 8-amino moiety is
1
a led to the formation of diaryl sulfone 3v in 77% necessary for an efficient sulfonylation. Reactions of
yield. the parent free 8-aminoquinoline 10a or an alkylated
To gain more insight into the reaction mechanism, derivative 10b did not afford the desired sulfonylated
a series of control experiments was performed. The products (Scheme 4c).
copper-catalyzed coupling of N-methylated quinoline
Next reactions with isotopically labelled substrates
8
, a substrate where bidentate chelation between both were performed (Scheme 5). When the sulfonylation
nitrogen atoms is blocked, did not afford any sulfony- of 1a was performed in d -HFIP no deuterium incor-
2
Scheme 3. Lithium–halogen exchange and direct lithiation approach to sulfones.
Adv. Synth. Catal. 0000, 000, 0 – 0
4
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÞÞ
These are not the final page numbers!

COMMUNICATIONS
asc.wiley-vch.de
Scheme 5. Deuteration and isotope effect experiments.
poration was observed in the product or the recov- fore we propose the following tentative mechanism
ered starting material, suggesting an irreversible (Scheme 7). Complexation of a copper(II) salt with 8-
cleavage of the CꢀH bond (Scheme 5a). No kinetic aminoquinoline 1 gives anionic imidate-copper(II)
isotope effect (KIE) was observed in an intermolecu- complex 13. Recent theoretical calculations have
lar competition experiment between amide 1a and the shown that coordination of the substrate 1 to copper
dideuterated substrate d -1a (Scheme 5b). These re- lowers the energy barrier for oxidation of the amino-
2
[
13a,d]
sults indicate that the cleavage of the CꢀH bond is quinoline and facilitates an intermolecular SET.
not the rate-limiting step.
Subsequently, the intermolecular SET between the
Performing the model reaction in the presence of amidoquinoline and either copper(II) or man-
the radical scavenger, 2,2,6,6-tetramethylpiperin-1-yl
oxyl (TEMPO) did not affect the yield, if only one
equivalent of TEMPO was used (Scheme 6a). Addi-
tion of three equivalents of the TEMPO completely
shut down the reaction. Since TEMPO can either
scavenge radical intermediates or deactivate the
ACHTUNGTRENNGNUg anese(III) furnishes the radical complex 14. Al-
copper catalyst or Mn(OAc) through redox processes
3
or the formation of metal complexes, this result does
not unambiguously prove the involvement of single
electron transfer (SET) processes or radical inter-
mediates. Therefore, additional experiments with 1,1-
diphenylethylene (DPE) (11) as radical trap were
conducted. Addition of 3 equivalents of DPE (11) to
our model reaction led to sharp decrease in yield to
19%. Interestingly the coupling product 12 could be
detected as side product (Scheme 6b). Reaction of
sulfinate 2a with DPE (11) in the absence of the ami-
noquinoline 1a furnished vinyl sulfone 12 in 46–54%
yield in the presence or absence of the copper catalyst
(
Scheme 6c). Formation of the addition product 12
suggests the involvement of a sulfonyl radical, which
could be easily generated upon single-electron oxida-
[
1]
tion of the sulfinate salt.
Considering our overall results and the recent re-
ports by Stahl and others on remote CꢀH functionali-
zations of 8-aminoquinolines under acidic condi-
[13]
tions,
the most plausible reaction pathway should
proceed via single-electron transfer processes. There- Scheme 6. Radical-trapping experiments.
Adv. Synth. Catal. 0000, 000, 0 – 0
5
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÞÞ
These are not the final page numbers!

COMMUNICATIONS
asc.wiley-vch.de
Scheme 7. Proposed mechanism.
2
+
3+
though both Cu and Mn are competent oxidants Mn(OAc) in other oxidative CꢀH functionalizations
3
for this reaction, oxidation by Mn(OAc)3 is more are currently under investigation in our laboratory.
likely to occur, due to the higher oxidation potential
3+ [17]
of Mn . This high oxidation potential might be the
cause for the observed fast CꢀH functionalization at Experimental Section
[
18]
room temperature. Single-electron oxidation of the
[
19]
sulfinate 2, most likely again with Mn(OAc)3, leads Typical Procedure
to the formation of sulfonyl radical 15. Addition of
An oven-dried 10-mL tube was charged with a magnetic stir-
ring bar, aminoquinoline derivative 1 (1.0 equiv., 0.2 mmol),
sodium sulfinate 2 (3.0 equiv., 0.6 mmol), CuCl2 (5.4 mg,
the radical 15 to intermediate 14 yields complex 16.
Loss of a proton, presumably via base-assisted depro-
tonation gives the anionic copper complex 17, which
0
.2 equiv.,
0.04 mmol),
Mn(OAc) ·2H O
(160.8 mg,
3
2
can undergo protonation to yield the desired product 3.0 equiv., 0.6 mml) and HFIP (0.1M referring to aminoqui-
3
and the regenerated catalyst. Alternatively a direct noline derivative, 2 mL). The tube was closed with a rubber
ligand exchange of 18 with starting material 1 could septum and the resulting reaction mixture was stirred at
room temperature for 90 min. After completion of the reac-
tion, the mixture was diluted with ethyl acetate and filtered
through a short plug of celite and silica gel. The filter pad
was rinsed with additional ethyl acetate and the combined
lead to complex 13, which can reenter the catalytic
cycle. Reaction of intermediate 14 with sulfonyl radi-
cal 15 at the C-7 position would furnish the observed
side-product of type 3aa.
filtrates were concentrated under reduced pressure. Purifica-
In summary, we have developed a novel, mild and
tion of the crude residue by flash column chromatography
efficient method for the remote sulfonylation of ami-
noquinolines with sodium sulfinates. The copper-cata-
lyzed reaction is simple to perform and proceeds
readily at room temperature. Various functional
groups are tolerated and the desired C-5 sulfonylated
aminoquinolines were obtained in high yields and re-
gioselectivities. In addition, the use of lithium sulfi-
nates, easily accessible from sulfur dioxide and orga-
nolithium reagents, enables the rapid synthesis of sul-
fones in two or three steps starting from simple build-
ing blocks. Essential for the rapid CꢀH functionaliza-
[20]
afforded the analytically pure product.
Acknowledgements
This work was financially supported by the Fonds der Chem-
ischen Industrie (Liebig Fellowship to G.M.), the Boehringer
Ingelheim Foundation (Exploration Grant to G. M.) and the
program of China Scholarships Council (PhD fellowship to
S. Liang, No. 201406240029). We would like to thank Prof.
Michael Gçbel (Goethe-University Frankfurt) for his sup-
tion at room temperature is the cooxidant,
Mn(OAc) . This facile manganese-mediated oxidation
3
offers new opportunities for the development of port, and BASF SE, Evonik Industries AG, and Rockwood
novel, mild CꢀH activations. Further applications of Lithium GmbH for the generous donation of chemicals.
Adv. Synth. Catal. 0000, 000, 0 – 0
6
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÞÞ
These are not the final page numbers!

COMMUNICATIONS
asc.wiley-vch.de
References
Lett. 2013, 15, 188; j) A. Shavnya, S. B. Coffey, A. C.
Smith, V. Mascitti, Org. Lett. 2013, 15, 6226; k) N. Mar-
graf, G. Manolikakes, J. Org. Chem. 2015, 80, 2582.
[
[
[
1] a) S. Patai, C. Z. Rappoport, J. M. Stirling, The Chemis-
try of Sulfones and Sulfoxides, Wiley, New York, 1988;
b) N. S. Simpkins, Sulphones in Organic Synthesis, Per-
gamon Press, Oxford, 1993.
2] G. La Regina, A. Coluccia, A. Brancale, F. Piscitelli, V.
Gatti, G. Maga, A. Samuele, C. Pannecouque, D.
Schols, J. Balzarini, E. Novellino, R. Silvestri, J. Med.
Chem. 2011, 54, 1587.
3] a) X. Codony, J. M. Vela, M. J. Ramirez, Curr. Opin.
Pharmacol. 2011, 11, 94; b) A. V. Ivachtchenko, E. S.
Golovina, M. G. Kadieva, V. M. Kysil, O. D. Mitkin,
S. T. Tkachenko, I. L. Okun, J. Med. Chem. 2011, 54,
[8] For selected reviews, see: a) K. M. Engle, T.-S. Mei, M.
Wasa, J.-Q. Yu, Acc. Chem. Res. 2012, 45, 788; b) L.
Ackermann, Chem. Rev. 2011, 111, 1315; c) C. Shen, P.
Zhang, Q. Sun, S. Bai, T. S. A. Hor, X. Liu, Chem. Soc.
Rev. 2015, 44, 291; d) X. X. Guo, D. W. Gu, Z. Wu, W.
Zhang, Chem. Rev. 2015, 115, 1622; e) S. A. Girard, T.
Knauber, C.-J. Li, Angew. Chem. 2014, 126, 76; Angew.
Chem. Int. Ed. 2014, 53, 74; f) R. Samanta, K. Matcha,
A. P. Antonchick, Eur. J. Org. Chem. 2013, 26, 5769;
g) J. Wencel-Delord, T. Drçge, F. Liu, F. Glorius,
Chem. Soc. Rev. 2011, 40, 4740.
8
161.
[9] a) X. Zhao, E. Dimitrijevi c´ , V. M. Dong, J. Am. Chem.
Soc. 2009, 131, 3466; b) O. Saidi, J. Marafie, A. E. W.
Ledger, P. M. Liu, M. F. Mahon, G. Kociok-Kçhn,
M. K. Whittlesey, C. G. Frost, J. Am. Chem. Soc. 2011,
133, 19298; c) Z. Wu, H. Song, X. Cui, C. Pi, W. Du, Y.
Wu, Org. Lett. 2013, 15, 1270; d) F. Xiao, H. Chen, H.
Xie, S. Chen, L. Yang, G.-J. Deng, Org. Lett. 2014, 16,
50; e) P. Katrun, C. Mueangkaew, M. Pohmakotr, V.
Reutrakul, T. Jaipetch, D. Soorukram, C. Kuhakarn, J.
Org. Chem. 2014, 79, 1778; f) A. M. A. Nassoy, P.
Raubo, J. P. A. Harrity, Chem. Commun. 2015, 51,
5914; g) W.-H. Rao, B.-B. Zhan, K. Chen, P.-X. Ling,
Z.-Z. Zhang, B.-F. Shi, Org. Lett. 2015, 17, 3552;
h) F. H. Xiao, S. Q. Chen, Y. Chen, H. W. Huang, G.-J.
Deng, Chem. Commun. 2015, 51, 652; i) K. Sun, X.-L.
Chen, X. Li, L.-B. Qu, W.-Z. Bi, X. Chen, H.-L. Ma, S.-
T. Zhang, B.-W. Han, Y.-F. Zhao, C.-J. Li, Chem.
Commun. 2015, 51, 12111; j) Y. Xu, P. Liu, S. L. Li, P.
Sun, J. Org. Chem. 2015, 80, 1269; k) V. Prakash Reddy,
R. Qiu, T. Iwasaki, N. Kambe, Org. Biomol. Chem.
2015, 13, 6803.
[10] a) J. Liu, L. Yu, S. Zhuang, Q. Gui, X. Chen, W. Wang,
Z. Tan, Chem. Commun. 2015, 51, 6418; b) W.-H. Rao,
B.-F. Shi, Org. Lett. 2015, 17, 2784; c) S. Liang, N.-W.
Liu, G. Manolikakes, Adv. Synth. Catal. 2016, 358, 159.
[11] a) V. G. Zaitsev, D. Shabashov, O. Daugulis, J. Am.
Chem. Soc. 2005, 127, 13154; b) M. Corbet, F. De
Campo, Angew. Chem. 2013, 125, 10080; Angew. Chem.
Int. Ed. 2013, 52, 9896.
[12] a) H.-W. Liang, K. Jiang, W. Ding, Y. Yuan, L. Shuai,
Y.-C. Chen, Y. Wei, Chem. Commun. 2015, 51, 16928;
b) H. Qiao, S. Sun, F. Yang, Y. Zhu, W. Zhu, Y. Dong,
Y. Wu, X. Kong, L. Jiang, Y. Wu, Org. Lett. 2015, 17,
6086; c) J. Wei, J. Jiang, X. Xiao, D. Lin, Y. Deng, Z.
Ke, H. Jiang, W. Zeng, J. Org. Chem. 2016, 81, 946;
d) J. Xu, C. Shen, X. Zhu, P. Zhang, M. J. Ajitha, K.-W.
Huang, Z. An, X. Liu, Chem. Asian J. 2016, 11, 882;
e) C. Xia, K. Wang, J. Xu, Z. Wei, C. Shen, G. Duan,
Q. Zhu, P. Zhang, RSC Adv. 2016, 6, 37173.
[
4] For selected recent examples, see: a) Y. Yang, Z. Chen,
Y. Rao, Chem. Commun. 2014, 50, 15037; b) Q. Lu, J.
Zang, F. Wei, Y. Qi, H. Wang, Z. Liu, A. Lei, Angew.
Chem. 2013, 125, 7297; Angew. Chem. Int. Ed. 2013, 52,
7
156; c) Q. Lu, J. Zang, G. Zhao, Y. Qi, H. Wang, A.
Lei, J. Am. Chem. Soc. 2013, 135, 11481; d) M. Amar-
nath Reddy, P. Surendra Reddy, B. Sreedhar, Adv.
Synth. Catal. 2010, 352, 1861; e) M. Catarinella, T.
Grꢁner, T. Strittmatter, A. Marx, T. U. Mayer, Angew.
Chem. 2009, 121, 9236; Angew. Chem. Int. Ed. 2009, 48,
9
072, and references cited therein.
[
[
[
5] a) A. Kar, I. A. Sayyed, W. F. Lo, H. M. Kaiser, M.
Beller, M. K. Tse, Org. Lett. 2007, 9, 3405; b) J. M.
Baskin, Z. Wang, Org. Lett. 2002, 4, 4423; c) W. Zhu,
D. Ma, J. Org. Chem. 2005, 70, 2696; d) S. Cacchi, G.
Fabrizi, A. Goggiamani, L. M. Parisi, R. Bernini, J.
Org. Chem. 2004, 69, 5608; e) S. Cacchi, G. Fabrizi, A.
Goggiamani, L. M. Parisi, Org. Lett. 2002, 4, 4719;
f) B. P. Bandgar, S. V. Bettigeri, J. Phopase, Org. Lett.
2
004, 6, 2105.
6] a) S. K. Aithagani, K. R. Yempalla, G. Munagala, R. A.
Vishwakarma, P. P. Singh, RSC Adv. 2014, 4, 50208;
b) V. G. Pandya, S. B. Mhaske, Org. Lett. 2014, 16,
3
1
836; c) N. Umierski, G. Manolikakes, Org. Lett. 2013,
5, 188; d) S. Liang, R.-Y. Zhang, L.-Y. Xi, S. Y. Chen,
X.-Q. Yu, J. Org. Chem. 2013, 78, 11874; e) K. M. Ma-
loney, J. T. Kuethe, K. Linn, Org. Lett. 2011, 13, 102;
f) R. Chawla, R. Kapoor, A. K. Singh, L. D. S. Yadav,
Green Chem. 2012, 14, 1308.
7] a) A. S. Deeming, C. J. Russell, M. C. Willis, Angew.
Chem. 2016, 128, 777; Angew. Chem. Int. Ed. 2016, 55,
7
47; b) A. Shavnya, K. D. Hesp, V. Mascitti, A. C.
Smith, Angew. Chem. 2015, 127, 13775; Angew. Chem.
Int. Ed. 2015, 54, 13571; c) M. W. Johnson, S. W.
Bagley, N. P. Mankad, R. G. Bergman, V. Mascitti, F. D.
Toste, Angew. Chem. 2014, 126, 4493; Angew. Chem.
Int. Ed. 2014, 53, 4404; d) E. J. Emmett, B. R. Hayter,
M. C. Willis, Angew. Chem. 2014, 126, 10211; Angew.
Chem. Int. Ed. 2014, 53, 10204; e) C. S. Richards-
Taylor, D. C. Blakemore, M. C. Willis, Chem. Sci. 2014,
[13] For other examples of remote C-5 functionalization of
8-aminoquinolines, see: a) A. M. Suess, M. Z. Ertem,
C. J. Cramer, S. S. Stahl, J. Am. Chem. Soc. 2013, 135,
9797; b) X. Cong, X. Zeng, Org. Lett. 2014, 16, 3716;
c) L. Zhu, R. Qiu, X. Cao, S. Xiao, X. Xu, C.-T. Au, S.-
F. Yin, Org. Lett. 2015, 17, 5528; d) H. Guo, M. Chen,
P. Jiang, J. Chen, L. Pan, M. Wang, C. Xie, Y. Zhang,
Tetrahedron 2015, 71, 70; e) H. Sahoo, M. K. Reddy, I.
Ramakrishna, M. Baidya, Chem. Eur. J. 2016, 22, 1592.
5
, 222; f) E. J. Emmett, B. R. Hayter, M. C. Willis,
Angew. Chem. 2013, 125, 12911; Angew. Chem. Int. Ed.
013, 52, 12679; g) B. N. Rocke, K. B. Bahnck, M. Herr,
2
S. Lavergne, V. Mascitti, C. Perreault, J. Polivkova, A.
Shavnya, Org. Lett. 2014, 16, 154; h) A. S. Deeming,
C. J. Russell, A. J. Hennessy, M. C. Willis, Org. Lett.
2
014, 16, 150; i) N. Umierski, G. Manolikakes, Org.
Adv. Synth. Catal. 0000, 000, 0 – 0
7
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÞÞ
These are not the final page numbers!

COMMUNICATIONS
asc.wiley-vch.de
[
14] For reviews on manganese in organic synthesis, see:
[16] J. Clayden, E. Baldwin, R. M. Willaims, Organolithium:
Selectivity for Synthesis, Pergamon, Oxford, 2002.
[17] E (Cu /Cu )=0.16 V (vs. SHE); E (Mn /Mn )=
a) A. S. Demir, M. Emrullahoglu, Curr. Org. Synth.
0
2+
+
0
3+
2+
2
1
007, 4, 321; b) M. Mondal, U. Bora, RSC Adv. 2013, 3,
8716; c) B. B. Snider, Chem. Rev. 1996, 96, 339.
1.51 V (vs. SHE).
[
15] For recent applications of manganese in oxidative CꢀH
functionalizations, see: a) A. S. Demir, ꢂ. Reis, M. Em-
rullahoglu, J. Org. Chem. 2003, 68, 578; b) X. Pan, M.
Lei, J. Zhou, W. Zhang, Tetrahedron Lett. 2009, 50, 347;
c) W. Xu, J. Zou, W. Zhang, Tetrahedron Lett. 2010, 51,
[18] Solely copper-promoted C-5ꢀH functionalizations of
aminoquinolines require higher temperatures of
[
12,13]
>
908C; see refs.
3+
[
19] For Mn -promoted sulfonyl radical formation, see:
a) C. Chuang, A. Tsai, M. Tsai, Tetrahedron 2013, 69,
2
639; d) K. Hattori, A. Ziadi, K. Itami, J. Yamaguchi,
3
293; b) K. Narasaka, T. Mochizuki, S. Hayakawa,
Chem. Commun. 2014, 50, 4105; e) T. Kagayama, A.
Nakano, S. Sakaguchi, Y. Ishi, Org. Lett. 2006, 8, 407;
f) X. Mu, J. Zou, Q. Qian, W. Zhang, Org. Lett. 2006, 8,
Chem. Lett. 1994, 23, 1705.
[
20] No special techniques were necessary to remove
copper or manganese from the products. All products
were obtained as colourless solids. Analysis of 3a with
atomic absorption spectroscopy (AAS) showed only
traces of Mn or Cu (<10 ppm).
5
291; g) J. Y. Kim, S. H. Cho, J. Joseph, S. Chang,
Angew. Chem. 2010, 122, 10095; Angew. Chem. Int. Ed.
010, 49, 9899; h) A. Nakatani, K. Hirano, T. Satoh, M.
Miura, J. Org. Chem. 2014, 79, 1377.
2
Adv. Synth. Catal. 0000, 000, 0 – 0
8
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÞÞ
These are not the final page numbers!

COMMUNICATIONS
Copper-Catalyzed Remote CꢀH Functionalization of 8-
9
Aminoquinolines with Sodium and Lithium Sulfinates
Adv. Synth. Catal. 2016, 358, 1 – 9
Shuai Liang, Georg Manolikakes*
Adv. Synth. Catal. 0000, 000, 0 – 0
9
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÞÞ
These are not the final page numbers!