K2S2O8-Promoted Direct C–H Phosphorylation of (Benzo)thiazoles

Article abstract of DOI:10.1002/ejoc.201700022

The direct phosphorylation of (benzo)thiazoles with various H-phosphine oxides was realized by using K₂S₂O₈ as the oxidant. A series of 2-phosphoryl (benzo)thiazoles were obtained in moderate to good yields.

Full text of DOI:10.1002/ejoc.201700022

DOI: 10.1002/ejoc.201700022
Communication
C–H Phosphorylation
K S O -Promoted Direct C–H Phosphorylation of
2
2 8
(
Benzo)thiazoles
[
a]
[a]
[a]
[a]
Weidong Lin, Feng Su, Hui-Jun Zhang,* and Ting-Bin Wen
Abstract: The direct phosphorylation of (benzo)thiazoles with oxidant. A series of 2-phosphoryl (benzo)thiazoles were ob-
various H-phosphine oxides was realized by using K S O as the tained in moderate to good yields.
2
2 8
Introduction
phosphine oxides.[9b] Recently, Wu et al. reported the first direct
route for the C–H phosphorylation of thiazoles with diarylphos-
phine oxides catalyzed by visible light along with 5 mol-%
Aromatic phosphorus compounds represent a class of ubiqui-
tous molecules in biochemistry and catalysis.
tion of these compounds through efficient C(sp )–P bond for-
mation is of great importance in organic chemistry. Since the
[
1,2]
The construc-
[9c]
eosin B. The phosphoryl radical generated from the reaction of
diarylphosphine oxides and silver salts may be involved in the
transformation. Recently, Yang and co-workers reported a tran-
sition-metal-free K S O -mediated oxidative arylphosphination
2
[
3]
pioneering work of Hirao et al. in 1981, plenty of synthetic
procedures based on the transition-metal-catalyzed cross-cou-
pling of aryl (pseudo)halides with H-phosphonates have been
2
2 8
[
10,11]
of activated N-substituted-N-arylacrylamide derivatives.
The reaction of HP(O)Ph with the sulfate radical anion derived
[
4]
2
developed. However, these methodologies are environmen-
tally and economically less attractive owing to the need for
prefunctionalization of Ar–H bonds and the use of a large
amount of base. Recently, two straightforward routes for the
from K S O may lead to the formation of a phosphoryl radical.
2
2 8
Encouraged by this work, we envisioned that the direct C–H
phosphorylation of (benzo)thiazoles might be realized through
a simple peroxodisulfate-promoted radical process (Scheme 1).
Herein, we report on the realization of this hypothesis.
2
direct phosphorylation of C(sp )–H bonds have received signifi-
cant attention. The first route relies on palladium-, copper-, or
rhodium-catalyzed C(sp )–H phosphorylation. The groups of
Yu and Murakami independently developed a route for the first
2
[5]
II
pyridine-directed Pd -catalyzed C–H phosphorylation of aryl
[
5b,5c]
C–H bonds.
The second route relies on the radical phos-
phorylation of (hetero)arenes. Several metal salts, such as Mn-
[
6]
[7]
[8]
(
OAc) /Co(OAc) , Mn(OAc)3, and peroxodisulfate/AgNO3,
2 2
were reported to promote the phosphorylation of (hetero)-
arenes with dialkyl phosphonates.
Scheme 1. C–H phosphorylation of (benzo)thiazoles.
2-Substituted benzothiazole derivatives are of particular in-
terest in pharmaceutical chemistry and materials science. Re-
cently, the direct C2 phosphorylation of benzothiazoles has at-
[
5d,9]
tracted much attention from synthetic chemists.
and his co-workers reported the first Pd-catalyzed direct phos-
phonation of azoles with dialkyl phosphites.
In 2012, Li
Results and Discussion
[
5d]
Our research commenced with the reaction between benzo-
thiazole (1a) and diphenylphosphine oxide (2a) in the presence
In 2014, Chen
and Qu et al. found that the direct C2 phosphorylation of
benzothiazoles could be realized by the reaction of benzothi-
azoles with dialkylphosphites and diphenylphosphine oxide by
using di-tert-butyl peroxide (DTBP) as a radical initiator. Later,
we developed a method for the AgNO -mediated direct phos-
of K S O under an argon atmosphere (Table 1, entries 1–5).
2
2 8
Phosphorylation product 3aa was obtained in 65 % yield upon
performing the reaction at 70 °C with the use of 2 equivalents
[
9a]
of K S O (Table 1, entry 1). Treatment of 1a with 2a in the
2 2 8
3
presence of 1 and 3 equivalents of K S O afforded 3aa in lower
phorylation of (benzo)thiazoles with various diaryl- and dialkyl-
2 2 8
yields (41 and 61 %, respectively; Table 1, entries 2 and 3). Per-
forming the reaction at 50 and 90 °C provided desired product
3aa in much lower yields (45 and 44 %, respectively; Table 1,
entries 4 and 5). To our delight, conducting the reaction of 1a
with 2a in air provided a much better yield of 3aa (71 %;
[
a] Department of Chemistry, College of Chemistry and Chemical Engineering,
Xiamen University,
Xiamen 361005, Fujian, P. R. China
E-mail: meghjzhang@xmu.edu.cn
http://chem.xmu.edu.cn/teacher.asp?id=287
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/ejoc.201700022.
Table 1, entry 6). However, the reaction under an O atmos-
2
phere gave 3aa in only 31 % yield (Table 1, entry 7). Moreover, if
Eur. J. Org. Chem. 2017, 1757–1759
1757
© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Communication
the reaction was performed for 12 or 36 h, the phosphorylation phosphine oxides, such as dicyclohexylphosphine oxide (2h), di-
product was afforded in a much lower yield (Table 1, entries 8 butylphosphine oxide (2i), and butyl(phenyl)phosphine oxide
and 9). Thereafter, other persulfate salts, including (NH ) S O
(2j), with benzothiazole (1a) were performed. Corresponding
and Na S O , were examined, but they were less effective than phosphorylation products 3ah, 3ai, and 3aj were obtained in
4
2 2 8
2
2 8
K S O (Table 1, entries 10 and 11). Various solvents such as moderate yields (39–44 %). Upon adding 4 Å molecular sieves
2
2 8
MeCN, 1,2-dichloroethane (DCE), 1,4-dioxane, EtOAc, and DMSO (100 mg) to the reactions, 3ah and 3ai were obtained in dra-
were screened, and MeCN proved to be the best choice matically increased yields (77 and 82 %, respectively). However,
(
Table 1, entries 12–15). Finally, the yield of isolated 3aa was both ethyl phenylphosphinate (2k) and diethyl phosphonate
further increased by changing the purification process (Table 1, (2l) reacted with 1a to form the corresponding products in
entry 16).
much lower yields (3ak, 32 %; 3al, 8 %).
Table 2. Substrate scope.[a,b]
Table 1. Optimization of the reaction conditions.[a]
Entry
1[
Oxidant (equiv.)
T [°C]
t [h]
Solvent
Yield[b] [%]
c]
K
2
K
2
K
2
K
2
K
2
K
2
K
2
K
2
K
2
S
2
S
2
S
2
S
2
S
2
S
2
S
2
S
2
S
2
O
8
O
8
O
8
O
8
O
8
O
8
O
8
O
8
O
8
(2)
(1)
(3)
(2)
(2)
(2)
(2)
(2)
(2)
70
70
70
50
90
70
70
70
70
70
70
70
70
70
70
70
24
24
24
24
24
24
24
12
36
24
24
24
24
24
24
24
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
DCE
65
41
61
45
44
71
31
53
64
33
35
36
[
[
[
[
c]
c]
c]
c]
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
[
d]
0
1
2
3
4
5
6
(NH
Na
4
)
2
S
2
O
(2)
8
(2)
2
S
2
O
8
K
2
K
2
K
2
K
2
K
2
S
2
2
2
2
2
O
8
O
8
O
8
O
8
O
8
(2)
(2)
(2)
(2)
(2)
S
S
S
S
1,4-dioxane 59
EtOAc
DMSO
MeCN
44
61
82
[e]
[
a] Reaction conditions: 1a (0.2 mmol), 2a (0.6 mmol), oxidant (0.4 mmol),
MeCN (1.5 mL), air. [b] Yield of isolated product. [c] Under an argon atmos-
phere. [d] Under an O atmosphere. [e] At completion of reaction, instead of
2
directly removing the solvent, the resulting mixture was washed with water
and extracted with EtOAc before column chromatography.
[
(
[
a] Reaction conditions: 1 (0.2 mmol), 2 (0.6 mmol), oxidant (0.4 mmol), MeCN
1.5 mL), air; Cy = cyclohexyl, 2-Np = 2-naphthyl. [b] Yield of isolated product.
c] 4 Å molecular sieves (100 mg).
To test the generality of this chemistry, benzothiazoles and
thiazoles with different substituents and various H-phosphine
oxides were screened (Table 2). Different ring-substituted
(
–Me, –OMe, –OEt, –F, –Br, –Cl, –CO Me, –NO ) benzothiazoles
2 2
The reactions of 1a with 2a in the presence of 2,2,6,6-tetra-
were suitable substrates for this reaction, although lower yields
of the desired products were obtained for benzothiazoles con-
taining electron-deficient substituents. Furthermore, thiazoles
also reacted with diphenylphosphine oxide and gave corre-
sponding 2-phosphorylation products 3ja–la in moderate
yields (36–49 %). Next, various H-phosphine oxides were exam-
ined. Diarylphosphine oxides containing electron-donating or
methylpiperidin-1-oxyl (TEMPO) and butylated hydroxytoluene
BHT) as radical scavengers were performed to gain mechanistic
insight into the C–H phosphorylation reaction [Equation (1)].
The yields of 3aa decreased dramatically, which is consistent
with a radical mechanism.
(
electron-neutral groups (4-Me, 3,5-Me , and 4-Ph) on the phenyl
2
ring were well tolerated and gave desired products 3ab–ad in
good yields (77–86 %). Furthermore, the reaction of benzo-
thiazole (1a) with diarylphosphine oxides containing electron-
withdrawing groups (4-F and 4-Br) proceeded smoothly and led
to the formation of 3ae and 3af in lower yields (3ae, 51 %; 3af,
(
1)
48 %). Notably, di(naphthalen-2-yl)phosphine oxide also re-
To explore the practical value of this K S O -mediated C–H
2
2 8
acted with benzothiazole (1a) and 4,5-dimethylthiazole (1l) to phosphorylation process, the phosphorylation of other hetero-
afford corresponding products 3ag and 3lg in moderate yields cycles such as benzothiophene, 2-methylthiophene, and benzo-
(
3ag, 68 %; 3lg, 63 %). In addition, the reactions of alkyl- furan with HP(O)Ph2 was examined (Scheme 2). The corre-
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1758 © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Communication
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Conclusions
[
In conclusion, we developed an efficient route for the K S O -
2
2 8
mediated direct C–H phosphorylation of (benzo)thiazoles. This
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2 2 8
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2
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product 3.
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We are thankful for financial support from the National Natural
Science Foundation of China (No. 21572188, 21302157) and
Fundamental Research Funds for the Central Universities (No.
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20720160049).
Keywords: Heterocycles · Oxidation · Phosphorylation ·
Radical reactions · Synthetic methods
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Received: January 8, 2017
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