Radical addition reactions of diphenylphosphine sulfide

Article abstract of DOI:10.1055/s-2005-921888

Radical additions of diphenylphosphine sulfide [Ph₂P(S)H] to various C=C bonds offers a general, mild and efficient approach to alkyl(diphenyl)phosphine sulfides. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2005-921888

LETTER
2981
Radical Addition Reactions of Diphenylphosphine Sulfide
Radical
Addition
R
n
eactions of
D
iphenylpho
r
sphine
S
e
ulfide w F. Parsons,*a David J. Sharpe,a Philip Taylorb
a
Department of Chemistry, University of York, Heslington, York, YO10 5DD, UK
Fax +44(1904)432516; E-mail: afp2@york.ac.uk
b
ICI Paints plc, Wexham Road, Slough, SL2 5DS, UK
Received 21 September 2005
investigated.4 Consequently, this paper discusses the rad-
ical addition of Ph2P(S)H to various C=C bonds to prepare
alkyl(diphenyl)phosphine sulfides, which are shown, for
the first time, to be useful synthetic intermediates.
Abstract: Radical additions of diphenylphosphine sulfide
[Ph2P(S)H] to various C=C bonds offers a general, mild and
efficient approach to alkyl(diphenyl)phosphine sulfides.
Key words: radical reaction, phosphorus hydride, C=C bonds
Initially, Ph2P(S)H was prepared by heating diphe-
nylphosphine with sulfur in degassed toluene.5 After re-
crystallisation (from acetonitrile), Ph2P(S)H was isolated
as a white solid in 87% yield.
One synthetic approach to organophosphorus compounds
involves addition of phosphorus hydrides to C=C bonds in
the presence of a radical initiator.1 In these chain reac-
tions, an intermediate phosphorus-centred radical is
formed from the phosphorus hydride (this may be a phos-
phine, a phosphine oxide, a hypophosphite, a thiophos-
phite or a phosphite). The organophosphorus product is
formed by addition of the phosphorus-centred radical to
the C=C bond followed by abstraction of a hydrogen atom
from the phosphorus hydride (this regenerates the phos-
phorus-centred radical, which continues the chain). How-
ever, not all phosphorus hydrides are equally reactive
towards C=C bonds. For example, diethyl thiophosphite
[(EtO)2P(S)H] adds more efficiently to electron-rich C=C
bonds than diethyl phosphite [(EtO)2P(O)H], and this can
be explained by the different strengths of the P–H bonds.2
Addition of Ph2P(S)H to 1-octene was then investigated at
room temperature in dioxane, using Et3B (2 × 0.3 equiv; 1
M solution in hexane) as the initiator (Scheme 1). After
stirring overnight, octyl(diphenyl)phosphine sulfide (1)
was isolated in 64% yield. In the absence of Et3B, the rad-
ical addition can be initiated by microwave irradiation.6
Irradiating a mixture of Ph2P(S)H (1.2 equiv) and 1-
octene (1.0 equiv) in degassed dioxane at 90 °C (in a
sealed tube), gave 1 in a similar yield of 62% after only 2
hours. The good yield of 1 shows that microwave irradia-
tion selectively forms the Ph2P(S)• radical.
Ph2P(S)
Ph2P(S)
2 (88%)‡
Ph2P(S)
3 (49%)‡
OBu
Ph2P(S)H
4 (38%)‡
(1.2 equiv)
Ph2P(S)
C6H13
C6H13
Et3B (2 x 0.3 equiv)/
1
Ph2P(S)
O2, r.t., dioxane (64%)
Ph2P(S)
Ph
Ph
Ph2P(S)
EtO2C
CO2Et
H
P(S)Ph2
5 (51%)*
6 (93%, Z:E = >20:1)*
7 (71%, dr = 10:1)‡
Ph2P(S)
Ph2P(S)
C6H13
C6H13
‡using 1.2 equiv of Ph2P(S)H
*using 3 equiv of Ph2P(S)H
Scheme 1
Figure 1
Recently, we have started to investigate how different
substituents on phosphorus affect the reactivity of the P–
H bond. For example, our calculations of bond dissocia-
tion energies (using density functional theory) show that
the P–H bond in diphenylphosphine sulfide [Ph2P(S)H] is
especially weak (ca. 302 kJ mol–1).3 The weak P–H bond
suggests that Ph2P(S)H may efficiently add to C=C bonds
by a radical mechanism under mild conditions, although
surprisingly, this type of radical reaction has not been well
Reaction of Ph2P(S)H (1.2 or 3 equiv) with a range of
electron-rich C=C bonds at room temperature (using
Et3B/O2 as the initiator) was then investigated and this
gave alkyl(diphenyl)phosphine sulfides 2–7 in reasonable
to excellent yield (Figure 1).7,8 Addition of Ph2P(S)H (1.2
equiv) to butyl vinyl ether gave 2 in an excellent yield of
88%, while reaction with cyclohexene and ethylidenecy-
clohexane gave 3 and 4, respectively, in lower yields.
Steric effects could in part, explain the lower yields of 3
and particularly 4. The more substituted the C=C bond,
the slower the rate of addition of the large Ph2P(S)• radical
and so addition to the trisubstituted C=C bond in ethyl-
SYNLETT 2005, No. 19, pp 2981–2983
0
1
.1
2
.2
0
0
5
Advanced online publication: 04.11.2005
DOI: 10.1055/s-2005-921888; Art ID: D28905ST
© Georg Thieme Verlag Stuttgart · New York

2982
A. F. Parsons et al.
LETTER
idenecyclohexane is expected to be particularly slow. The reaction using either Ph2PH/base or PPh3.10 Although
stability of the intermediate carbon-centred radical may radical addition of Ph2P(O)H1b to an unsaturated com-
also affect product yields as illustrated by the higher yield pound offers a one-step approach to alkyl(diphenyl)phos-
of 6 (from phenylacetylene) compared to 5 (from styrene). phine oxides, radical addition of Ph2P(S)H followed by
Addition of Ph2P(S)• to phenylethyne forms a more reac- oxidation using MCPBA can be more efficient. For exam-
tive carbon-centred radical than that generated by addition ple, whereas reaction of 3 equivalents of Ph2P(S)H with
to styrene. This results in a faster rate of hydrogen atom phenylethyne forms 6 in an excellent 93% yield, the same
abstraction [from Ph2P(S)H] by the more reactive radical reaction with 3 equivalents of Ph2P(O)H gave the phos-
to form the (diphenyl)phosphine sulfide adduct. For addi- phine oxide adduct in only 67% yield.
tion to styrene, a relatively slow rate of hydrogen atom ab-
Ph2P(O)
Ph2P(O)
straction by the intermediate benzylic radical may lead to
unwanted side reactions and this could explain the lower
yield of 5. Radical cyclisation of 1,6-dienes is also possi-
ble and Ph2P(S)H (1.2 equiv) reacts with diethyl diallyl-
malonate to afford cyclopentane 7 in 71% yield (via a
chair-like transition state).2a
C6H13
CO2Me
14
15
Figure 3
Alkyl(diphenyl)phosphine oxides have been shown to be
useful synthetic intermediates. For example, a-deprotona-
tion of alkyl(diphenyl)phosphine oxides followed by
reaction with an aldehyde, ketone or an epoxide has been
shown by Horner and Lythgoe, and more recently by
Warren and co-workers, to form C–C bonds.11 When 14
was deprotonated and then reacted with cyclohexanone,
after work up, the expected b-hydroxy-phosphine oxide
16 was isolated in 74% yield. Interestingly, when
octyl(diphenyl)phosphine sulfide 1 was reacted with
cyclohexanone under the same conditions as for 14, the
corresponding b-hydroxy-phosphine sulfide 17 was
isolated in 57% yield (Scheme 2).12
Ph2P(S)
Ph2P(S)
Ph2P(S)
10 (92%)
CO2Me
CO2Me
CN
8 (99%)
9 (92%)
Ph2P(S)
Ph2P(S)
Ph2P(S)
CONH2
O
O
N
O
O
N
Ph
Ph
11 (72%)
12 (72%)
13 (57%, dr = 10:1)
Figure 2
Ph2P(X)
Reaction of Ph2P(S)H (3 equiv) with a range of electron-
poor C=C bonds at room temperature (using Et3B/O2 as
the initiator) was then investigated and this gave
alkyl(diphenyl)phosphine sulfides 8–13 in good to excel-
lent yield (Figure 2).9 Addition of Ph2P(S)H to methyl
acrylate gave 8 in quantitative yield. It is interesting to
compare this reaction with the addition of (EtO)2P(S)H (5
equiv) to methyl acrylate, which gave a mixture of prod-
ucts derived from addition to one (40%), two (40%) and
three acrylate molecules (20%, a similar result has been
reported previously1d). The selective formation of 8 shows
that the carbon-centred radical produced from radical
addition to the acrylate abstracts a hydrogen atom more
rapidly from Ph2P(S)H than from (EtO)2P(S)H. The
Ph2P(S)H also efficiently adds to methyl methacrylate,
acrylonitrile, acrylamide and N-phenylmaleimide to form
9, 10, 11 and 12, respectively. Also, addition to 3-methyl-
N-phenylmaleimide forms adduct 13 – the lower yield of
13 compared to 12 presumably reflects the different reac-
tivities of the intermediate carbon-centred radicals.
C6H13
BuLi (1.1 equiv),
THF, –78 °C
Ph2P(X)
HO
C6H13
then
cyclohexanone (1.4 equiv),
–78 °C to r.t.
1, X = S
14, X = O
16, X = O (74%)
17, X = S (57%)
Scheme 2
In conclusion, the radical addition of Ph2P(S)H (an easily
handled solid) to C=C bonds has been shown to provide a
direct, efficient and particularly mild approach to
alkyl(diphenyl)phosphine sulfides. It is noteworthy that
under radical conditions, Ph2P(S)H adds efficiently to
C=C bonds containing both electron-donating and elec-
tron-withdrawing groups. The resulting alkyl(diphe-
nyl)phosphine sulfides are useful synthetic intermediates
as they can be alkylated at the a-position, converted into
alkyl(diphenyl)phosphine oxides or reduced to phos-
phines using for example, Raney nickel.13 We are current-
ly investigating the use of this methodology to prepare
important target molecules.
Our studies then explored new reactions of the
alkyl(diphenyl)phosphine sulfides. First, oxidation of 1
and 8 using MCPBA (CH2Cl2, r.t.) was shown to produce
the corresponding phosphine oxides 14 and 15, respec- Acknowledgment
tively, in quantitative yields (Figure 3). This offers an
We would like to thank the EPSRC and ICI for funding, Chris Jes-
alternative approach to alkyl(diphenyl)phosphine oxides,
which are traditionally prepared in two steps from haloal-
kanes – the first step involves a nucleophilic substitution
sop for investigating the reaction of (EtO)2P(S)H with methyl acry-
late, and Dimitrios Pantazis and Dr. John McGrady (University of
York) for calculation of the BDE.
Synlett 2005, No. 19, 2981–2983 © Thieme Stuttgart · New York

LETTER
Radical Addition Reactions of Diphenylphosphine Sulfide
2983
3.21–3.08 [2 H, m, P(S)CH2–CH], 2.52–2.41 [1 H, m,
P(S)CH2–CH], 1.18 (3 H, d, J = 7 Hz, CH2–CH–CH3).
References
13C NMR (100.6 MHz, CDCl3): d = 175.8 (d, 3JC–P = 9.5 Hz,
O=C–O–CH3), 133.1 (d, 1JC–P = 80.5 Hz, Cq Ar), 132.3 (d,
1JC–P = 80.5 Hz, Cq Ar), 131.6 (d, 4JC–P = 3.0 Hz, CH Ar),
131.5 (d, 4JC–P = 3.0 Hz, CH, Ar), 131.3 (d, 2JC–P = 10.5 Hz,
2 × CH Ar), 131.0 (d, 2JC–P 10.0 Hz, 2 × CH Ar), 128.7 (d,
3JC–P 12.0 Hz, 2 × CH Ar), 128.5 (d, 3JC–P = 12.0 Hz, 2 × CH
Ar), 51.9 (O–CH3), 35.5 [d, 1JC–P = 57 Hz, P(S)CH2], 34.3
[d, 2JC–P = 1 Hz, P(S)CH2–CH], 19.4 (d, 3JC–P = 8.5 Hz,
CH2–CH–CH3). 31P NMR (161.9 MHz, CDCl3): d = 41.3
[Ph2P(S)]. MS (CI, NH3): m/z (%) = 319 (100), 218 (17).
HRMS: m/z calcd for C17H19O2PS: [M + H+] 319.0922 (0.2
ppm); found: [M + H+] 319.0921.
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(3) Pantazis, D.; McGrady, J. E. unpublished results.
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(8) Typical Procedure.
To diphenylphosphine sulfide (0.327 g, 3 equiv, 1.5 mmol)
in a N2 flushed flask was added non-degassed dioxane (2
mL), followed by methyl methacrylate (0.053 mL, 0.5
mmol). Then, Et3B (1 M solution in hexane, 0.15 mL, 0.3
equiv, 0.15 mmol) was added and the reaction was left to stir
for 4 h. After this time a further portion of Et3B (1 M solution
in hexane, 0.15 mL, 0.3 equiv, 0.15 mmol) was added, and
the mixture was left to stir for 16 h. The reaction mixture was
then concentrated in vacuo to afford the crude product.
Following column chromatography (4:1, PE–EtOAc),
methyl 3-(diphenylphosphorothioyl)-2-methylpropanoate
(9) was isolated as a colourless oil (0.147 g, 92%); Rf = 0.2
(4:1, PE–EtOAc). IR (thin film): nmax = 3054 (m), 2975 (m),
2949 (m), 1731 (s, C=O), 1436 (s, P–Ph), 1309 (m), 1274
(m), 1211 (s), 1158 (s), 1102 (s), 1027 (m), 998 (m) cm–1.
1H NMR (400 MHz, CDCl3): d = 7.91–7.80 (4 H, m, 4 × CH
Ar), 7.54–7.41 (6 H, m, 6 × CH Ar), 3.46 (3 H, s, O–CH3),
(12) Deprotonation of alkyl(diphenyl)phosphine sulfides and
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P.; Mathey, F. Can. J. Chem. 1982, 60, 840.
(13) See for example: Gilbertson, S. R.; Chang, C.-W. T. J. Org.
Chem. 1998, 63, 8424.
Synlett 2005, No. 19, 2981–2983 © Thieme Stuttgart · New York