Rhodium-catalyzed addition reaction of diphosphine disulfide to aldehydes and ketones

Article abstract of DOI:10.1016/j.tetlet.2009.03.135

In the presence of RhH(PPh₃)₄ and 1,2-bis(diphenylphosphino)ethane, tetramethyldiphosphine disulfide and aldehydes were added producing [1-(dimethylthiophosphinoyloxy)alkyl]dimethylphosphine sulfides in high yields. Acetophenones wit

Full text of DOI:10.1016/j.tetlet.2009.03.135

Tetrahedron Letters 50 (2009) 3639–3640
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Tetrahedron Letters
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Rhodium-catalyzed addition reaction of diphosphine disulfide to aldehydes
and ketones
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, 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:
In the presence of RhH(PPh3)4 and 1,2-bis(diphenylphosphino)ethane, tetramethyldiphosphine disulfide
and aldehydes were added producing [1-(dimethylthiophosphinoyloxy)alkyl]dimethylphosphine sulfides
in high yields. Acetophenones with electron-withdrawing p-groups also yielded 1,2-adducts.
Ó 2009 Published by Elsevier Ltd.
Received 21 January 2009
Revised 12 March 2009
Accepted 13 March 2009
Available online 25 March 2009
Geminal-phosphorus-phosphorusoxy compounds, the formal
adducts of P–P and C@O compounds, are a group of organophos-
phorus compounds, that have attracted interest in regard to their
biological activity.1 Several methods of synthesis have been re-
phosphorus compounds via P–P bond cleavage. In this Letter, we
describe a novel and fundamental rhodium-catalyzed carbonyl
addition reaction of a P–P compound: The addition reaction of
tetramethyldiphosphine disulfide12 to aldehydes and ketones
giving [1-(dimethylthiophosphinoyloxy)alkyl]dimethylphosphine
sulfide (Table 1). Such diphosphine disulfide adducts with alde-
hydes and ketones were not known before. This is a convenient
method for the synthesis of polyphosphorus compounds from sim-
ple aldehydes and ketones. It should also be noted that transition
metal catalysis can be used for such carbonyl addition reaction of
P–P compounds.
ported: (1) phosphorylation of a
-hydroxyphosphorus compounds2,
(2) hydrophosphorylation of acylphosphorus compounds1,3, and
(3) phosphorylation of acid chlorides and derivatives.4,5 It is often
observed in these methods that the initially formed 1-hydroxy-
1,1-diphosphorus compounds are rearranged to form geminal-
phosphorus-phosphorusoxy compounds under basic conditions.
It appeared, however, to us that the addition reaction of P–P com-
pounds to aldehydes and ketones may be a straightforward meth-
od, because the organic substrates are readily available (Scheme 1).
Unfortunately, such reaction has very few precedents, and noncat-
alyzed addition reaction of (CF3)2PP(CF3)2 and acetone has been re-
cently reported.6,7
C
O
Rh cat
P
P
C
O
P
P
+
During the course of our study on the development of transi-
tion-metal-catalyzed methods for the synthesis of organophospho-
rus compounds,8 the metathesis and addition reactions with
concomitant P–P bond cleavage have become important. We
reported the rhodium-catalyzed reaction of 1-alkynes and tetra-
phenydiphosphine in the presence of a nitrobenzene yielding
1-phosphinoyl-1-alkynes.9 This reaction proceeded via the metal-
catalyzed addition of the P–P bond with the nitrobenzene followed
by the C–H substitution of 1-alkynes. A single-bond metathesis
reaction of the diphosphine disulfide P–P bond and the disulfide
S–S bond giving thiophosphinates was also developed.10 Recently,
the rhodium-catalyzed C–P bond-forming reaction of 1,2-alkadi-
enes with diphosphine disulfide has been reported,11 which
involved P–P bond cleavage and the transfer of the phosphorus
group to the unsaturated compounds. Thus, rhodium complexes
were found to be excellent catalysts for the synthesis of organo-
Scheme 1.
Table 1
Rhodium-catalyzed addition reaction of tetramethyldiphosphine disulfide and
aldehydes
S
PMe2
RhH(PPh3)4 (2.5 mol%)
dppe (5 mol%)
R
S
S
+
O
Me2P PMe2
RCHO
PMe2
S
THF, refl., 2 h
Entry
R
Yield (%)
1
2
3
4
5
6
Ph
99
98
94
92
97
81
p-MeOC6H4
p-BrC6H4
n-C6H13
Ph(CH2)2
cyclo-C6H11
* 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 2009 Published by Elsevier Ltd.
doi:10.1016/j.tetlet.2009.03.135

3640
M. Arisawa, M. Yamaguchi / Tetrahedron Letters 50 (2009) 3639–3640
ing
[1-(dimethylthiophosphinoyloxy)alkyl]dimethylphosphine
S
Me
O
sulfides in high yields. The rhodium catalyst is involved in the P–P
bond cleavage and carbonyl addition of two phosphorus groups.
Synthesis of [1-(dimethylthiophosphinoyloxy)heptyl]dimethyl-
phosphine sulfide. Into a two-necked flask were placed RhH(PPh3)4
(2.5 mol %, 7.2 mg) and dppe (5 mol %, 5.0 mg) in distilled THF
(1 mL) under an argon atmosphere, and the solution was stirred
at room temperature for 1 min. Then, tetramethyldiphosphine
PMe2
RhH(PPh3)4 (7.5 mol%) Ar
dppe (15 mol%)
S
S
+
Me2P PMe2
ArCOCH3
PMe2
S
THF, refl., 2 h
Ar = p-CF3C6H4 90%
Ar = p-NCC6H4 95%
disulfide (0.25 mmol, 46.6 mg) and heptanal (0.25 mmol, 34.9 ll)
Scheme 2.
were added, and the solution was heated at reflux for 2 h. The sol-
vent was removed under reduced pressure, and the residue was
purified by flash column chromatography on silica gel giving the
product (69.1 mg, 92%) as a colorless solid. Mp 43.5–44.0 °C (hex-
ane). 1H NMR (400 MHz, CDCl3) d 0.89 (3H, t, J = 6.8 Hz), 1.27–1.32
(4H, m), 1.33–1.52 (4H, m), 1.72 (3H, d, J = 12.4 Hz), 1.77 (3H, d,
J = 12.4 Hz), 1.92 (6H, d, J = 13.2 Hz), 1.83–1.98 (1H, m), 2.02–
2.13 (1H, m), 5.04 (1H, dddd, J = 16.0, 8.8, 4.4, 2.4 Hz). 13C NMR
(100 MHz, CDCl3) d 14.0, 17.7 (d, J = 53.0 Hz), 19.3 (d, J = 53.8 Hz),
22.5, 24.7 (d, J = 76.6 Hz), 25.5 (d, J = 69.7 Hz), 26.1 (d, J = 9.9 Hz),
29.0, 29.8, 31.5, 75.3 (d, J = 65.2, 8.3 Hz). 31P NMR (162 MHz, CDCl3)
d 42.8 (d, J = 14.7 Hz), 97.4 (d, J = 14.9 Hz). IR (KBr) 2927, 2857,
1417, 1289, 947, 910 cmÀ1. MS (EI) m/z 300 (M+, 55%), 207
(M+ÀPSMe2, 75%), 93 (M+À207, 100%). HRMS Calcd for
C11H26OP2S2: 300.0901. Found: 300.0908.
RhH(PPh3)4 (2.5 mol %) and 1,2-bis(diphenylphosphino)ethane
(dppe, 5 mol %) were treated in THF for 1 min at room temperature,
to which an equimolar mixture of benzaldehyde and tetrame-
thyldiphosphine disulfide in THF was added. After refluxing in
THF for 2 h, [1-(dimethylthiophosphinoyloxy)benzyl]dimethyl-
phosphine sulfide was obtained in 99% yield (Table 1, entry 1).
31P NMR spectroscopy indicated the presence of two peaks at d
43.7 and 99.8 with J = 25 Hz. The P–H coupling constants J = 15.6
and 6.0 Hz were observed at the benzylic proton by 1H NMR spec-
troscopy. 13C NMR absorption of the benzylic carbon exhibited the
P–C coupling constants J = 64.5 and 6.9 Hz. The rhodium complex
and dppe were both essential for the reaction, and no reaction oc-
curred in the absence of either substance. Other metal complexes
in the presence of dppe exhibiting similar activity including
RhH(CO)(PPh3)3 and Rh(NO)(PPh3)4, whereas Rh(acac)(CH2@CH2),
RhCl(PPh3)3, [Rh(cod)(NH3)2]PF6, [Rh(OAc)2]2, Pd2(dba)3, and
PdCl2(PPh3)2 were ineffective.
The initial treatment of the rhodium complex and dppe was
essential for obtaining reproducible results. This probably reflects
the importance of the Rh–dppe complex formation in a sufficient
amount. The effect of the phosphine ligand was critical, and
bidentate ligands with diphenylphosphino groups attached by
two carbon atoms exhibited catalytic activity, such as cis-1,2-
bis(diphenylphosphino)ethylene (dppv) and 1,2-bis(diphenylphos-
phino)benzene (dppBz). Other bidentate ligands, dppm, dppp,
dppb, and dppf, as well as monodentate ligands, (p-MeOC6H4)3P
and (p-ClC6H4)3P, were not effective.
The reaction proceeded with several aldehydes as summarized
in Table 1 giving the 1,2-adducts in high yields. The electronic ef-
fect of the p-substituent of benzaldehydes was relatively small (en-
tries 1–3). Aliphatic aldehydes also underwent a smooth addition
reaction (entries 4–6).
This reaction was generally inert to ketones, and acetophenone
did not give the adduct under the metal-catalyzed conditions.
However, it was observed that acetophenones possessing elec-
tron-withdrawing cyano and trifluoromethyl groups at the p-posi-
tion reacted with diphosphine disulfide, giving the 1,2-adducts in
high yields, provided that the catalyst loading was sufficiently high
(Scheme 2).
Acknowledgments
This work was supported by JSPS (Nos. 16109001 and
17689001) and WPI Initiative, MEXT Japan. M.A. expresses her
thanks to the Grant-in-Aid for Scientific Research on Priority Areas,
‘Advanced Molecular Transformation of Carbon Resources’ from
MEXT (Nos. 18037005 and 19020008).
References and notes
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Also see Ref. 4.
As for the mechanisms, the involvement of the rearrangement
reaction from 1-hydroxy-1,1-diphosphorus compounds to the
products is unlikely under the metal-catalyzed conditions. Step-
wise addition and concerted carbonyl addition mechanism are
conceivable. In either case, it is notable that the rhodium complex
can participate in the bond formation of phosphorus and oxygen
atoms as well as phosphorus and carbon atoms.
8. Arisawa, M.; Yamaguchi, M. J. Synth. Org. Chem., Jpn. 2007, 65, 1213; Arisawa,
M.; Yamaguchi, M. Pure Appl. Chem. 2008, 80, 993.
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In summary, a rhodium complex catalyzed the addition reaction
of tetramethyldiphosphine disulfide to aldehydes and ketones giv-