Silver-mediated direct phosphorylation of benzothiazoles and thiazoles with diarylphosphine oxides

Article abstract of DOI:10.1039/c4cc10017d

A silver nitrate-mediated, efficient phosphorylation of benzothiazoles and thiazoles with diarylphosphine oxides was developed. This process provides a convenient route for the synthesis of a variety of 2-diarylphosphoryl benzothiazoles and thiazoles which are promising precursors of a series of hemilabile P,N-ligands with small bite angles. This journal is

Full text of DOI:10.1039/c4cc10017d

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Silver-mediated direct phosphorylation of
benzothiazoles and thiazoles with
Cite this:DOI: 10.1039/c4cc10017d
diarylphosphine oxides†
Received 16th December 2014,
Accepted 20th January 2015
Hui-Jun Zhang,* Weidong Lin, Zhengjian Wu, Wenqing Ruan and Ting-Bin Wen*
DOI: 10.1039/c4cc10017d
www.rsc.org/chemcomm
A silver nitrate-mediated, efficient phosphorylation of benzothiazoles
and thiazoles with diarylphosphine oxides was developed. This process
provides a convenient route for the synthesis of a variety of 2-diaryl-
phosphoryl benzothiazoles and thiazoles which are promising pre-
cursors of a series of hemilabile P,N-ligands with small bite angles.
The construction of C(sp2)–P bonds represents an important
transformation in synthetic chemistry because of its prevalence
in a wide range of biologically active molecules, pharmaceuticals,
phosphine-containing ligands, and functional materials.1,2 Transi-
tion metal-catalyzed phosphonation of aryl (pseudo)halides has
provided a useful tool for the synthesis of aromatic organophos-
phorus compounds.3 Recently, palladium-catalyzed cross dehydro-
Scheme 1 Phosphonation of benzothiazoles.
On the other hand, since the pioneering work of Jason and
genative coupling reaction of (het)aromatic compounds with Fields in 1962,5 radical phosphonation of (hetero)arenes has
phosphites has emerged as an economically attractive alterna- attracted significant attention. Several metal salts were found to
tive, which avoids the need for prefunctionalization of (het)Ar–H be effective for the generation of phosphonyl radicals.6,7 In
to aryl (pseudo)halides.4 However, in most cases, a large excess 2006, Ishii developed a Mn(II)/Co(II)/O2-catalyzed phosphonation
of silver salts or K2S2O8 had to be used as an oxidant. Moreover, to reaction of arenes with dialkyl phosphites.6c Subsequently, Zou
avoid the deactivation of the palladium catalysts by H-phosphonates, and Zhang et al. reported a Mn(OAc)3-promoted phosphonation
a relatively large amount of ligand should be used.4c,d In 2012, of heterocycles, such as thiazoles, furans, and pyrroles, with
Li et al. reported the first example of palladium-catalyzed direct diethyl phosphites.6d However, for these two strategies, aliphatic
2-phosphonation of azoles with dialkyl phosphites (Scheme 1).4c acid was normally used as solvent, which is not suitable for acid
In this transformation, the addition of 30 mol% proline or sensitive substrates. Recently, a silver-catalyzed dehydrogenative
2,20-bipyridine as a ligand and 3 equiv. of K2S2O8 as an oxidant cross-coupling reaction of dialkyl phosphites with heteroarenes
was necessary. In addition, rather than H-phosphonates, the was developed by Huang and his coworkers based on the previous
direct coupling of diarylphosphine oxides with azoles, which work of Effenberger.7a,b Peroxodisulfate was used to oxidize silver(I)
may provide a direct route to the synthesis of a variety of 2-diaryl- to silver(II) which may further oxidize the dialkyl phosphite to an
phosphoryl azoles, was not involved in their work.4c
electrophilic cation radical.7b Notably, the phosphorus substrates in
these transformations were limited to dialkyl phosphites. Recently,
Yang reported a silver-catalyzed carbon–phosphorus functionaliza-
tion of alkenes using Ph2P(O)H.8 Duan also developed a silver-
mediated C–H/P–H functionalization reaction of arylphosphine
oxides with internal alkynes.9 It is believed that a nucleophilic
phosphoryl radical was generated from the reaction between silver
salts and diarylphosphine oxides through the formation of silver
diarylphosphine oxides. In this context, with our continued interest
in the synthesis of 2-substituted benzothiazoles and also encouraged
by Chang’s work on silver-mediated direct amination of azoles,10,11
Department of Chemistry, College of Chemistry and Chemical Engineering, Xiamen
University, Xiamen 361005, Fujian, P. R. China. E-mail: meghjzhang@xmu.edu.cn,
chwtb@xmu.edu.cn; Fax: +86 5922186 295; Tel: +86 5922182 635
† Electronic supplementary information (ESI) available: General and experi-
mental information on optimization studies and procedures for phosphorylation
of benzothiazoles, characterization data (1H NMR, 13C NMR, 31P NMR, HRMS) for
all new compounds, single crystal X-ray structure analysis of 3ia and complex 6.
CCDC 1039491 and 1038973. For ESI and crystallographic data in CIF or other
electronic format see DOI: 10.1039/c4cc10017d
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Table 1 Optimization of the reaction conditionsa
Table 2 Investigation of the scope in benzothiazolesa
Entry
Oxidant
Solvent
t (h)
Yieldb (%)
Entry
1
Substrate
Product
Yieldb (%)
86 (89)c
1
2
3
4
AgOAc
Ag2O
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
DCE
24
24
24
24
24
24
24
12
36
24
24
24
24
24
24
39
35
33
8
Ag2CO3
AgOTf
AgNO3
AgNO3
AgNO3
AgNO3
AgNO3
AgNO3
AgNO3
AgNO3
AgNO3
AgNO3
AgNO3
5
65
32
48
55
56
72
44
57
39
29
34
6c
7d
8
2
3
4
5
6
7
63
9
10e
11
12
13
14
15
74
DMF
1,4-Dioxane
PhMe
EtOAc
69
a
Reaction conditions: 1a (0.2 mmol), 2a (0.4 mmol), oxidant (0.2 mmol),
85
solvent (1.5 mL), 90 1C. b Isolated yield. In air. d 1.5 equiv. of AgNO3.
c
e 3 equiv. of 2a.
90 (92)c
we envisioned that the nucleophilic addition of phosphoryl
radicals to benzothiazoles followed by oxidative aromatization
may lead to the formation of 2-phosphorylated benzothiazoles.
Herein, we introduce a silver-mediated direct phosphorylation
of benzothiazoles and thiazoles with diaryl phosphine oxides
under mild conditions without the addition of any other oxidants
(Scheme 1).
72
23
8
a
Reaction conditions: 1a (0.2 mmol), 2a (0.6 mmol), AgNO3 (0.2 mmol),
b
c
MeCN (1.5 mL), 90 1C. Isolated yield. Yields of 2.00 mmol scale
reactions (0.65 g of 3ba and 0.72 g of 3ga).
In an initial experiment, benzothiazole 1a was treated with
diphenylphosphine oxide (Ph2P(O)H, 2a) in the presence of
1 equiv. of AgOAc in acetonitrile at 90 1C (Table 1, entry 1). To benzothiazoles survived well in this transformation (entries 3–6).
our delight, the desired 2-diphenylphosphinyl benzothiazole Interestingly, 4,5-dimethylthiazole could also react with Ph2P(O)H
3aa was obtained in 39% yield after 24 h. Then several silver under the standard conditions affording the desired product 3ha in
salts were tested and AgNO3 was proved to be the best oxidant 72% yield (entry 7). In addition, treatment of the simple thiazole
(entries 2–5). The desired product 3aa was obtained in 65% with diphenylphosphine oxide gave the corresponding product
yield in the presence of 1 equiv. of AgNO3 (entry 5). Notably, a 3ia in only 23% yield perhaps due to the formation of other
similar reaction performed in air gave the desired product in regioisomers (entry 8). We have also tested the scalability of this
only 32% yield (entry 6). The addition of 1.5 equiv. of AgNO3 transformation with 2.00 mmol scale synthesis of 3ba in 89%
resulted in a lower yield of 48% (entry 7). Moreover, lower yields yield (0.65 g) and 3ga in 92% yield (0.72 g), respectively. Furthermore,
were also observed after 12 or 36 h indicating that the reaction the reaction of benzoxazole with diphenylphosphine oxide under the
time is also crucial for the coupling (entries 8 and 9). Delight- optimized conditions was also performed. Disappointingly, the
edly, when 3 equiv. of 2a was used, the yield of 3aa increased to desired phosphorylation product was not observed.
72% (entry 10). Furthermore, a range of solvents were screened
Subsequently, different diarylphosphine oxides were subjected
and acetonitrile was proved to be the most suitable solvent to the established reaction conditions (Table 3). Both para- and
(entries 11–15). Other metal salts, such as Mn(OAc)3, Cu(OAc)2, meta-methyl substituents on the phenyl ring have little effect on
CuCl2 and FeCl3, were also tested and none of them gave better the reaction and the corresponding products (3ab and 3ac)
results (see the ESI†).
were obtained in high yields (entries 1 and 2; 71% and 82%).
With the optimized conditions in hand, we examined the The electron-withdrawing para-fluoro group was also compatible
reactions of diphenylphosphine oxide with various benzothiazoles and the corresponding product 3ad was isolated in 51% yield
(Table 2). Both electron-rich and electron-deficient substituents on (entry 3). However, treatment of the diarylphosphine oxide
the phenyl rings of benzothiazoles were tolerated. Phosphorylation involving a para-bromo substituent with benzothiazole 1a
of both 6-methoxy and 6-methyl-substituted benzothiazoles afforded the desired product 3ae in only 23% yield (entry 4). In
afforded the corresponding products 3ba and 3ca in high yields addition, di(naphthalen-2-yl)phosphine oxide could react with
(entries 1 and 2). Several electron-withdrawing groups, such as both benzothiazole and 4,5-dimethylthiazole and lead to the
fluoro-, bromo-, chloro-, and methoxycarbonyl-groups, on the corresponding product in moderate yields (entries 5 and 6).
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Table 3 Investigation of the scope in diarylphosphine oxidesa
Entry
1
Substrate
Product
Yieldb (%)
71
Scheme 2 Investigation on the reaction mechanism.
2
82
51
3
4
Scheme 3 Proposed mechanism.
23
39
benzothiazole 1a could be further oxidized by AgNO3 to form the
desired product 3aa. To our surprise, no phosphorylation product
was detected after 24 h, which suggested that perhaps the phos-
phoryl radical was not involved in the reaction process. Afterwards,
the reaction of 1a with Ph2(O)PAg and Ph2(O)PH was also performed,
which only led to the formation of 3aa in 18% yield (eqn (2)).
Furthermore, different from Yang’s results,8a addition of several
nitrates, such as Mg(NO3)2 and Zn(NO3)2, as additives could not
promote the reaction (see the ESI†). Based on these experiments,
a plausible mechanism for the dehydrogenative cross-coupling is
proposed as shown in Scheme 3. Firstly, the thiazole ring is
activated through the coordination of N atoms with the Ag(I)
salt to form intermediate A.12 Then the nucleophilic addition of
the diphenylphosphine oxide to A leads to the formation of
intermediate B, which undergoes oxidative aromatization in the
presence of Ag(I) to give the final product 3.11a
5
6
63
42
7
8
19
92
9
a
Reaction conditions: 1a (0.2 mmol), 2a (0.6 mmol), AgNO3 (0.2 mmol),
b
MeCN (1.5 mL), 90 1C. Isolated yield.
Furthermore, to explore the potential utility of benzo[d]thiazol-2-
yldiarylphosphines as versatile ligands in coordination chemistry,
several experiments were performed (Scheme 4).2c,13 Using Beller’s
method,14 2-diphenylphosphinyl benzothiazole 3aa could be
reduced with tetramethyldisiloxane in the presence of 10 mol%
Cu(OTf)2 affording the corresponding phosphine ligand 5 in 60%
yield. Treatment of [Ru(cymene)Cl2]2 with excess of 5 led to the
Furthermore, the reaction between ethyl phenylphosphinate and
benzothiazole 1a produced 3ag in 42% yield (entry 7). Notably, under
the standard conditions, the phosphorylation of benzothiazoles with
diethyl phosphonate produced 3ah in only 19% yield (entry 8). To
our surprise, the reaction between dibutylphosphine oxide 2i and
benzothiazole 1a gave the desired product 3ai in 92% yield (entry 9).
In order to gain insight into the mechanism, several control
experiments were carried out (Scheme 2). Firstly, an efficient radical
scavenger BHT was introduced into the reaction between 1a and 2a,
which afforded the phosphorylation product 3aa in only 38% yield
(eqn (1)). Moreover, it is known that diphenylphosphine oxide
could react with AgNO3 leading to the formation of silver complex
Ph2(O)PAg (4).8 In this regard, Ph2(O)PAg was prepared according to
a previous report8a and added to the reaction of 1a in the presence
of AgNO3 at 90 1C (eqn (2)). It was supposed that the 2-phosphoryl
benzothiazoline radical intermediate derived from the nucleo-
philic addition of the corresponding phosphoryl radical on the Scheme 4 Preparation of ruthenium complex 7.
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formation of a neutral P-coordinated ruthenium(II) complex 6.15
Further treatment of complex 6 with AgSbF6 gave rise to the
additional coordination of the benzothiazole nitrogen atom to
ruthenium to afford the corresponding cationic ruthenium
complex 7. Complexes 6 and 7 are potential catalyst precursors
for hydrogenation of olefins.16,17
In summary, we have developed a facile and efficient method
for the preparation of various benzo[d]thiazol-2-yldiarylphosphine
oxides through silver mediated direct phosphorylation of benzo-
thiazoles and thiazoles. This method is compatible with the
reported Pd-catalyzed reactions,4c which may produce a more
convenient route to the synthesis of a series of novel P,N-ligands.
Further investigations on the scope and exact mechanism of this
method and the applications of the P,N ligands are underway in
our laboratory.
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We are grateful for the financial support from the Natural
Science Foundation of China (No. 21302157), the National Basic
Research Program of China (973 Program, No. 2012CB821600), the
Program for Changjiang Scholars and Innovative Research Team in
University (PCSIRT), NFFTBS (No. J1310024), and Fundamental
Research Funds for the Central Universities (No. 2013121015).
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