Radical-based reduction of phosphine sulfides and phosphine selenides by (Me3Si)3SiH

Article abstract of DOI:10.1016/S0040-4039(00)01759-7

Tris(trimethylsilyl)silane reacts with phosphine sulfides and phosphine selenides under free radical conditions to give the corresponding phosphines in good yields. Stereochemical studies on P-chiral phosphine sulfides show these reductions proceed with retention of configuration. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)01759-7

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 9899–9902
Radical-based reduction of phosphine sulfides and
phosphine selenides by (Me3Si)3SiH
Roberto Romeo,a,b Lucyna A. Wozniakc and Chryssostomos Chatgilialoglua,*
aI.Co.C.E.A., Consiglio Nazionale delle Ricerche, Via P. Gobetti 101, 40129 Bologna, Italy
bDipartimento Farmaco-Chimico, Universita` di Messina, Via SS. Annunziata, 98100 Messina, Italy
cCentre of Molecular and Macromolecular Studies, Department of Bioorganic Chemistry,
Polish Academy of Sciences, Sienkiewicza 112, 90-363 Lo´dz, Poland
Received 4 September 2000; accepted 4 October 2000
Abstract
Tris(trimethylsilyl)silane reacts with phosphine sulfides and phosphine selenides under free radical
conditions to give the corresponding phosphines in good yields. Stereochemical studies on P-chiral
phosphine sulfides show these reductions proceed with retention of configuration. © 2000 Elsevier Science
Ltd. All rights reserved.
Keywords: phosphine sulfides; reduction; radical reactions.
In recent years radical reactions have proven to be valuable in organic synthesis. The selective
removal of functional groups or atoms to generate carbon-centered radicals and the formation
of carbonꢀcarbon bonds has been the workhorse for those who employ radical chemistry in
synthesis of complex molecules.1 Furthermore, great progress in the stereoselective control of
radical reactions has also been accomplished.2 On the other hand, the radical chemistry
associated with functional groups attached to atoms other than carbon has received much less
attention. In this communication, we report preliminary results concerning a novel radical chain
reduction of phosphine sulfides and phosphine selenides to the corresponding phosphines as well
as the stereochemical outcome.
We reasoned that (Me3Si)3SiH3 could have the right properties to achieve the reduction of
phosphine sulfides and phosphine selenides by a radical chain reaction based on the following
observations: (i) In view of the affinity of silyl radicals for sulfur and selenium atoms,4 the
’
addition of the (Me3Si)3Si radical to the PꢁX double bond to give a phosphoranyl intermediate
1 is expected to be a facile process (Scheme 1).
* Corresponding author. Tel: 39-051-6398309; fax: 39-051-6398349; e-mail: chrys@area.bo.cnr.it
0040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)01759-7

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Scheme 1.
(ii) The a-fragmentation of phosphoranyl radicals is well documented5 and radical 1 is likely
to undergo this path for certain R substituents. (iii) The formed sulfur-centered radical 2 is
known to undergo an efficient 1,2-shift of the Me3Si group from the silicon to the sulfur atom
to give radical 3.4,6 Hydrogen abstraction from the silane should regenerate the (Me3Si)3Si
’
radicals, thus completing the cycle of a chain reaction.7,8
The feasibility of reduction with (Me3Si)3SiH was tested using triphenyl phosphine sulfide and
triphenyl phosphine selenide. The reactions of Ph3PꢁS or Ph3PꢁSe with an equimolar amount of
(Me3Si)3SiH in toluene at 80°C in the presence of AIBN as the radical initiator gave crystalline
Ph3P in 96% yield. On the other hand, treatment of the resulting crude mixture with 1 equiv. of
BH3–THF afforded the corresponding stable phosphine–borane complex in 90% yield (Scheme
2 and Table 1). The reaction was still efficient with n-Bu3PꢁS and n-Bu3PꢁSe, although longer
reaction times and higher concentrations of the reducing agent were required. In the case of
mixed alkyl and aryl substituted phosphine sulfides, intermediate reactivities were observed
(Table 1). It is also worth mentioning that the reactions with Ph3PꢁO and n-Bu3PꢁO were
unsuccessful, even at temperatures as high as 150°C.
Scheme 2.
Table 1
Reaction of RR%R¦PꢁX with (Me3Si)3SiH
RR%R¦PꢁX
Time (h)/equiv. (Me3Si)3SiHa
RR%R¦P, yield (%)
RR%R¦P–BH3, yield (%)d
n-Bu3PꢁS
5/3
5/1
3/1
1/1
6/3
2/1
–
75
88
96
90
75
–
Met-BuPhPꢁS
MePhArPꢁSb
Ph3PꢁS
90c
–
96d
–
n-Bu3PꢁSe
Ph3PꢁSe
96d
a Reaction conditions: 0.2 M of RR%R¦PꢁX and AIBN (10 mol%) in deoxygenated toluene at 80°C.
b Ar=o-MeOꢀC6H4.
c 1H NMR yields using (PhCH2)2O as internal standard.
d Isolated yields after solvent evaporation and flash chromatography of the crude reaction mixture.
For the purpose of stereochemical studies, (−)-(Sp)-o-anisylphenylmethylphosphine sulfide (4)
was prepared by the Corey protocol.9 Furthermore, the (−)-(Sp)-4 enantiomer (92% e.r.) was
converted into the opposite (+)-(Rp)-4 (88% e.r.)10,11a in a three-step procedure and in 96%

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overall yield as follows: (a) Stereoretentive oxidation of (−)-(Sp)-4 with OXONE® into the
corresponding phosphine oxide.12 (b) Reduction of the phosphine oxide with Cl3SiH in the
presence of Et3N to phosphine, according to Horner and Balzer with inversion of configuration
at the phosphorus center.13 (c) Oxidation of the phosphine with elemental sulfur with retention
of configuration (Scheme 3).14
Scheme 3. Reagents and conditions: 2 equiv. OXONE, THF, 2 h; (b) 5 equiv. Cl3SiH, 5 equiv. Et3N, PhH, 80°C, 3
h; (c) 1 equiv. S8, PhH, 80°C, 3 h; (d) (Me3Si)3SiH, AIBN, PhH, 80°C, 3 h; (e) BH3–THF, rt, 2 h
Each enantiomer 4 was treated separately with (Me3Si)3SiH under the conditions elaborated
earlier for analogous racemic compounds (Table 1) and the enantiomeric phosphines were
isolated and analyzed as stable BH3 complexes 5.9,11b The conversion of (+)-(Rp)-4 into
(+)-(Sp)-5 was stereoselective whereas the reduction of (−)-(Sp)-4 afforded (−)-(Rp)-5 with some
decrease of enantiomeric purity in 3 h (Scheme 3). When these reactions were interrupted after
1.5 hours (at ca. 50% of the consumption of the starting material), both of them were
stereospecific, which indicates some epimerization by secondary processes occurring in the
full-time reaction of (−)-(Sp)-4. A detailed study on the stereospecificity of these reactions is in
progress.
The reduction of phosphine sulfides to the corresponding phosphines is of general interest,
since today P-chiral phosphines play a fundamental role in the development of enantioselective
transition metal catalysts15 and phosphine sulfides can be considered as the safe and stable
precursors thereof. So far, the most effective method of reduction of P-chiral phosphine sulfides
relies on the use of hexachlorodisilane as developed by Mislow and co-workers.16 However, our
radical method achieves comparable stereochemical outcomes using milder conditions and
therefore is recommended for sensitive substrates.
Acknowledgements
This work was carried out within the scientific cooperation joint project CNR–PAS. We thank
Marco Ballestri for technical assistance and Professor Wojciech J. Stec for helpful discussions.
References
1. For general review on radical reactions, see: (a) Giese, B. Radicals in Organic Synthesis: Formation of
CarbonꢀCarbon Bonds; Pergamon: Oxford, 1988. (b) Curran, D. P. In Comprehensive Organic Synthesis; Trost,
B. M.; Fleming I., Eds.; Pergamon: Oxford, 1991; Vol. 4, p. 715. (c) Motherwell, W. B.; Crich, D. Free Radical
Chain Reactions in Organic Synthesis; Academic: London, 1992. (d) Chatgilialoglu, C.; Renaud, P. In General
Aspects of Free Radical Chemistry; Alfassi, Z. B., Ed.; Wiley: London, 1999; Chapter 15; pp. 501–538.
2. Curran, D. P.; Porter, N. A.; Giese, B. Stereochemistry of Radical Reactions; VCH: Weinheim, 1995.

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3. (a) Chatgilialoglu, C. Acc. Chem. Res. 1992, 25, 188. (b) Chatgilialoglu, C.; Ferreri, C.; Gimisis, T. The Chemistry
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7. It is worth noting that the reaction sequence in Scheme 1 is in the opposite direction of the well-known
desulfuration of alkylthiyl radicals by tricoordinated phosphorus compounds. See: Walling, C.; Rabinowitz, R.
J. Am. Chem. Soc. 1957, 79, 5326. Walling, C.; Pearson, M. S. J. Am. Chem. Soc. 1964, 86, 2262.
8. The reduction of phosphine sulfides by Me3SnH using AIBN in stoichiometric quantities (which indicates a
non-chain process) is reported to be a sluggish process. See: Avar, G.; Neumann, W. P. J. Organomet. Chem.
1977, 131, 215.
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10. (Sp) and (Rp) refer to the configuration at phosphorus and e.r. refers to the enantiomeric ratio.
11. Analytical conditions: (a) HPLC, 25 cm chiral column Chiralpack AD, eluent: i-PrOH/hexane (20:80), flow 0.7
mL/min.; elution times: (−)-(Sp)-4 at 12.1 min, (+)-(Rp)-4 at 15.18 min. (b) HPLC, 25 cm Chiral Daicel OJ
column, eluent: i-PrOH/hexane (40:60), flow 0.7 mL/min; elution times: (−)-(Rp)-5 at 22.0 min, (+)-(Sp)-5 at 39.4
min.
12. Wozniak, L. A.; Stec, W. J. Tetrahedron Lett. 1999, 40, 2637.
13. Horner, L.; Balzer, W. D. Tetrahedron Lett. 1965, 1157.
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New York, 1996; pp. 147–180.
16. Zon, G.; DeBruin, K. E.; Naumann, K.; Mislow, K. J. Am. Chem. Soc. 1969, 91, 7023.
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