Metal-catalyzed phosphinyl ester forming reaction of alcohols and phenols with diphosphine disulfides and a dioxide

Article abstract of DOI:10.1016/j.tetlet.2010.07.040

Transition metal complexes catalyzed the dialkylphosphinothioation reaction of alcohols and phenols with tetraalkyldiphosphine disulfides in high yields. Phenols were reacted in the presence of RhH(PPh₃)₄ and 1,2-bis(dimethylphosphino)ethane under THF reflux, and alcohols with Pd(OAc)₂ and 1,2-bis(diphenylphosphino)benzene under chlorobenzene reflux. Primary alcohols reacted faster than secondary alcohols under these conditions, and protected tyrosine and serine were phosphinothioated with minimal racemization. Tetraphenyldiphosphine dioxide also underwent the P-O bond formation reaction.

Full text of DOI:10.1016/j.tetlet.2010.07.040

Tetrahedron Letters 51 (2010) 4840–4842
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Metal-catalyzed phosphinyl ester forming reaction of alcohols and phenols
with diphosphine disulfides and a dioxide
Mieko Arisawa a, Masahiko Yamaguchi a,b,
*
a Department of Organic Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba, Sendai 980-8578, Japan
b WPI Research Center, Advanced Institute for Materials Research, Tohoku University, Aoba, Sendai 980-8577, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Transition metal complexes catalyzed the dialkylphosphinothioation reaction of alcohols and phenols
with tetraalkyldiphosphine disulfides in high yields. Phenols were reacted in the presence of RhH(PPh3)4
and 1,2-bis(dimethylphosphino)ethane under THF reflux, and alcohols with Pd(OAc)2 and 1,2-bis(diphen-
ylphosphino)benzene under chlorobenzene reflux. Primary alcohols reacted faster than secondary alco-
hols under these conditions, and protected tyrosine and serine were phosphinothioated with minimal
racemization. Tetraphenyldiphosphine dioxide also underwent the P–O bond formation reaction.
Ó 2010 Published by Elsevier Ltd.
Received 31 May 2010
Revised 3 July 2010
Accepted 8 July 2010
Available online 11 July 2010
Synthetic organophosphorus esters derived from phosphinic
acid, phosphonic acid, and their sulfur analogs have attracted
much interest with regard to their function as biologically active
substances and materials.1 In general, such esters are synthesized
from alcohols and phenols by treatment with organophosphorus
reagents possessing highly reactive leaving groups, typically chlo-
ride, in the presence of stoichiometric amounts of a base.1–4 Be-
cause the method employs basic reaction conditions and
inevitably forms salts as a byproduct, it is desirable that the P–O
bond formation be conducted without using a base. It was consid-
ered that the development of an appropriate combination of a cat-
alyst and a phosphorus reagent could provide an efficient method
for phosphorus ester formation.
The P–P bond-containing compounds in general were not reac-
tive with alcohols and phenols. An occasional example of the phos-
phorus ester formation is known using compounds possessing
polarized P–P bonds in the presence of a large excess of simple
alcohols or alkoxides;6 and photolysis of diphosphines and poly-
phosphines in alcohol give phosphorus esters.7 We have been
examining transition-metal-catalyzed methods for the synthesis
of organophosphorus compounds, and have showed that rhodium
complexes can cleave P–P bonds and transfer the phosphorus
group to other molecules.5 The results of this study shows that
transition metal complexes can catalyze the effective phosphinyl
ester formation reaction of alcohols and phenols using diphosphine
disulfides and a dioxide. It should be noted that the P–O bonds
were formed employing stoichiometric amounts of hydroxy com-
pounds and diphosphines. In addition, we show that transition me-
tal complexes can catalytically promote the esterification reaction
of alcohols and phenols without a base.
When an equimolar mixture of p-methoxyphenol and tetrame-
thyldiphosphine disulfide8 in THF was heated at reflux for 3 h in
the presence of RhH(PPh3)4 (1 mol %) and 1,2-bis(dimethylphosph-
ino)ethane (dmpe, 2 mol %), O-(p-methoxyphenyl) dimethylphos-
phinothioate was obtained in 100% yield; it was accompanied by
PHSMe2 in 72% yield (Table 1, entry 1). No reaction occurred in
the absence of the rhodium complex. Other metal complexes
exhibiting similar activity in the presence of dmpe were
RhH(CO)(PPh3)3 and Rh(acac)(CH2@CH2). In contrast, RhCl(PPh3)4,
Rh(acac)3, [Rh(cod)(PPh3)2]PF6, and [Rh(OAc)2]2 were less effective.
The effect of the phosphine ligand was also critical, and other
bidentate ligands with phosphino groups separated by two carbon
atoms such as 1,2-bis(diethylphosphino)ethane (depe), 1,2-
bis(diphenylphosphino)ethane (dppe), and 1,2-bis(diphenylphos-
Table 1
Rhodium-catalyzed phosphinothioation reaction of phenols
RhH(PPh3)4 (1 mol%)
S
S
S
S
dmpe (2 mol%)
THF, refl., 3 h
+
+
ArOH
R'2P PR'2
ArO PR'2 R'2P
H
Entry
R0
Ar substituent
Yield (%)
1
2
3
Me
Me
Me
Et
p-Me
p-(t-Bu)
p-MeO
p-MeO
100
98
99
99
4
5
6
7
8
9
10
11
Me
Me
Me
Me
Me
Me
Me
p-Cl
p-Ph
m-Me
m-Ph
o-Me
o-Ph
98
96
97
97
86
97
(S)-p-C6H4CH2CH(NHBoc)CO2Me
98, 99% ee
* Corresponding author. Tel.: +81 22 795 6812; fax: +81 22 795 6811.
E-mail address: yama@mail.pharm.tohoku.ac.jp (M. Yamaguchi).
0040-4039/$ - see front matter Ó 2010 Published by Elsevier Ltd.
doi:10.1016/j.tetlet.2010.07.040

M. Arisawa, M. Yamaguchi / Tetrahedron Letters 51 (2010) 4840–4842
4841
phino)benzene (dppBz) exhibited modest catalytic activity forming
the product in 30–60% yield.
S
S
S
S
O
PMe2
Pd cat.
OH
O
PMe2 +
O
+
Me2P PMe2
The reaction proceeded with substituted phenols, as summa-
rized in Table 1, giving the aryl esters in high yields. The electronic
effect of the p-substituent was small (entries 1, 3, and 5). Tetra-
ethyldiphosphine disulfide reacted as well as the tetramethyl
derivative (entry 4). The dimethylthiophosphination reaction of
protected tyrosine proceeded effectively without racemization
(entry 11).
OH
OH
PMe2
S
6%
79%
10%
1 eq
2 eq
78%
Scheme 1.
The reaction of alcohols and the diphosphine disulfide exhibited
a slightly different nature. Benzyl alcohol and tetramethyldiphos-
phine disulfide in chlorobenzene were heated at reflux for 3 h in
the presence of Pd(OAc)2 (1 mol %) and dppBz (2 mol %), and O-
benzyl dimethylphosphinothioate was obtained in 99% yield (Ta-
ble 2, entry 1). Higher temperature was required for the reaction
of the alcohol compared with that of the phenols and 21% of the
product was obtained at 80 °C. Use of RhH(PPh3)4 in place of
Pd(OAc)2 gave a modest yield of the product, probably because of
catalyst deactivation. The ligand effect was again examined, and
only 6% yield of the product was obtained without dppBz. It was
confirmed that dppBz itself did not catalyze the reaction.
The method using Pd(OAc)2 and dppBz was applied to primary
alcohols giving phosphinothioates in high yield (entries 1, 3, 4, 5,
and 7). Tetraethyldiphosphine disulfide reacted at slower rates,
and required 16 h for completion (entries 2 and 6). Because the
palladium complex catalyzed the reaction of p-methoxyphenol in
refluxing chlorobenzene giving the phosphinothioate quantita-
tively (entry 8), phenol could be reacted using either catalyst.
The reactions of secondary and tertiary alcohols were slow, as indi-
cated by the reactions of 2- and 1-adamantanol (entries 9 and 11).
1,2-Propanediol gave a mono-phosphinothioated product in 79%
yield accompanied by a bis-product in 6% yield, when 1 equiv of
the diphosphine was employed (Scheme 1). The use of 2 equiv of
the reagent gave predominantly a bis-phosphinylated product.
The exceptional reactivity of cyclopentanol can probably be as-
cribed to less steric congestion of the substrate (Table 2, entry
10). A serine derivative was dimethylphosphinothioated with min-
imal racemization despite the relatively high reaction temperature
(entry 12). A protected sugar also reacted smoothly (Scheme 2).
Although some differences in the reactivity were observed in rho-
dium- and palladium-catalyzed reactions, both catalyzed the phos-
phinothioation reaction. Such metal effects appear to be general in
the reactions of organophosphorus compounds.9
S
O
PMe2
O
O
OH
O
O
S
S
Pd cat.
O
O
+
Me2P PMe2
O
O
O
93%
O
Scheme 2.
RhH(PPh3)4 (2.5 mol%)
dmpe (5 mol%)
O
O
Ph2P
p-MeOC6H4OH +
p-MeOC6H4O PPh2
94%
THF, refl., 3 h
2
Pd(OAc)2 (5 mol%)
dppBz (10 mol%)
O
PhCH2O PPh2
80%
O
PhCH2OH
+
Ph2P
PhCl, refl., 3 h
2
Scheme 3.
phosphinates in high yields (Scheme 3). Thus, the P@S and P@O
bonds in the diphosphine exert a small effect on the catalytic phos-
phinothioation reaction.
In summary, rhodium and palladium complexes catalyzed the
phosphinyl ester formation reaction of alcohols and phenols with
diphosphine disulfides and a dioxide in high yields. It should be
emphasized that the transition metal catalysis can be used for
the esterification reaction of O–H compounds, and such methodol-
ogy has an advantage of avoiding the use of a base. The catalysts
probably participated both in the generation of reactive metal
phosphorus intermediates and in the activation of the O–H group.
An oxidative addition reaction of a polyphosphine with a rho-
dium(I) complex has recently been reported.10 Depending on the
ligand, palladium and rhodium complexes can react with free alco-
hols and phenols either as acids or bases,11 and such an activated
species could also react with activated phosphorus intermediates.
In addition to tetraalkyldiphosphine disulfides, tetraphenyldi-
phosphine dioxide reacted with an alcohol and a phenol giving
Table 2
Palladium-catalyzed phosphinothioation reaction of alcohols
Typical experimental procedures
Pd(OAc)2 (1 mol%)
S
S
S
S
dppBz (2 mol%)
In a two-necked flask equipped with a reflux condenser were
placed RhH(PPh3)4 (1.0 mol %, 11.5 mg), tetramethyldiphosphine
disulfide (1.0 mmol, 186.2 mg), and p-methoxyphenol (1.0 mmol,
124.1 mg) under an argon atmosphere. Dry THF (2 mL) and dmpe
+
+
ROH
R'2P PR'2
RO PR'2
R'2P H
C6H5Cl, refl., 3 h
Entry
R0
R
Yield (%)
1
2
Me
Et
PhCH2
PhCH2
99
(2.0 mol %, 3.4 lL) were added, and the solution was heated at re-
91a
flux for 3 h. The solvent was removed under reduced pressure, and
the residue was purified by flash column chromatography on silica
gel giving O-(p-methoxyphenyl) dimethylphosphinothioate
(212.8 mg, 99%) as a colorless solid and dimethylphosphine sulfide
(67.3 mg, 72%) as a pale yellow oil.
3
4
5
6
Me
Me
Me
Et
p-MeOC6H4CH2
n-C4H9
n-C8H17
98
72
83
n-C8H17
81a
7
8
9
10
11
12
Me
Et
Me
Me
Me
Me
1-Adamantylmethyl
p-MeOC6H4
2-Adamantyl
cyclo-C5H9
1-Adamantyl
82
99
23
71
Acknowledgments
7
(S)-MeO2CCH(NHBoc)CH2
93, 95%ee
This work was supported by a Grant-in-Aid for Scientific Re-
search (Nos. 21229001 and 22689001), the GCOE program, and
a
Reaction time: 16 h.

4842
M. Arisawa, M. Yamaguchi / Tetrahedron Letters 51 (2010) 4840–4842
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Supplementary data
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