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Current Organic Chemistry, 2017, 21, 569-585

REVIEW ARTICLE
ISSN: 1385-2728
eISSN: 1875-5348

The Reduction of Tertiary Phosphine Oxides by Silanes Impact

Factor:
1.949

BENTHAM
SCIENCE

Tamara Kovács and György Keglevich*

Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, 1521 Budapest, Hungary
Abstract: The deoxygenation of tertiary phosphine oxides is an important reaction, as it provides useful interme-
diates and reagents, makes the available P-ligands useful in transition metal complexes, and regenerates wastes
produced by the Wittig-, Mitsunobu and Appel reactions. Methods for the reduction of the P=O moiety
comprising different metal and other hydrides, silanes and other species are surveyed, especially from the point of
ARTICLE HISTORY view of environmentally-friendly (green) chemistry, and practical applicability to be able to select the most
Received: October 04, 2016 suitable reagent. Oxalyl chloride converting the phosphine oxide to the corresponding chlorophosphonium salt
Revised: October 28, 2016 may also be used, but this step should be followed by a reduction. Obviously, silanes are the reagents of choice.
Accepted: October 31, 2016
The most widespread, but corrosive trichlorosilane may be substituted by more userfriendly alternatives, such as
DOI: phenylsilane, tetramethyldisiloxane (TMDS) and polymethylhydrosiloxane (PMHS). The latter two species
10.2174/1385272821666161108121
532 are cheap, but of lower reactivity, however, they may be useful in microwave-assisted and solvent-free deoxy-
genations. Stereochemical and mechanistic aspects of the most often applied silane reductions are also discussed.
In most cases, the P-configuration is preserved.
Current Organic Chemistry

Keywords: Phosphine oxides, reduction, phosphines, silanes, hydrides, user-friendly methods.

1. INTRODUCTION • Hydrophosphination of alkenes and alkynes (2) [20, 21]

Tertiary phosphines are widely used as ligands in transition
metal complexes and as extractants, or as starting materials and
C C + HP CH C P
reagents in syntheses [1-4]. The transition metal (most frequently
Pd, Pt, Rh) complexes may be applied in homogeneous catalytic
hydrogenation, hydroformylation, hydrosilylation or palladium- (2)
catalyzed coupling reactions. Tertiary phosphines may be the
starting materials for quaternary phosphonium salts used as surfac- HP
tants, ionic liquids or phase transfer catalysts. C C + HP CH CH P bisadduct
Representative examples for the application of tertiary
phosphines as reagents in various organic reactions include the • Reduction of phosphine oxides (3) [22-24]
Wittig reaction (formation of C=C bonds), the Mitsunobu reaction
(formation of C–O or C–N bonds), and Appel-type reactions (for- Y1 Y1
mation of C–halogene bonds) [5-11]. Unfortunately, the mentioned reduction
Y2 P O Y2 P (3)
reactions are of poor atom economy, leading to substantial amounts
Y3 Y3
of phosphine oxide waste. The phosphine oxides formed are unde-
sirable by-products, and should be regenerated and recycled [12].
The simplest method to regenerate phosphines from phosphine In this article, the preparation of phosphines by deoxygenation
oxides is reduction. The deoxygenation of tertiary phosphine oxides is overviewed. It is noteworthy that the reduction of P=O bonds is
is also applied in the final step of the preparation of phosphines, if not simple, because these bonds are highly stable thermodynami-
P(O)Cl3 is the starting material [13-18]. cally. With a bond energy of around 502 kJ mol–1, the P=O bonds
Three major methods are used for the synthesis of phosphines: are more stable than other functional groups (e.g. the C=O moiety
• Substitution reactions of carbon electrophiles with alkali that is easily reduced by catalytically activated hydrogen, or sodium
metal phosphides (A)/(1), or substitution reactions of car- borohydride) [25]. A rather widespread method for the deoxygena-
bon nucleophiles with PCl derivatives (B)/(1) [19] tion of phosphine oxides involves the use of silanes [26-28].
A B
Besides the wide range of silanes displaying different reactiv-
Y1X + MPY22 Y1PY22 Y1M + ClPY22

MX
MCl ities, other reducing agents may also be used, which are discussed
Y1 = alkyl, aryl Y1 = alkyl, aryl (1)
in this review article.
X = Cl, Br M = Li, MgBr
Y2 = aryl Y2 = alkyl, aryl
M = Na, K 2. DIRECT REDUCTION OF PHOSPHINE OXIDES
2.1. Deoxygenation of Phosphine Oxides Using Hydrides
*Address correspondence to this author at the Department of Organic Chemistry and
Technology, Budapest University of Technology and Economics, 1521 Budapest, Metal hydrides, such as aluminium hydrides (e.g. lithium alu-
Hungary; Tel: +36-1-463-1111(5883); Fax: +36-1-463-3648;
E-mail: gkeglevich@mail.bme.hu minium hydride (LAH) alone [29], or combined with cerium chlo-

1875-5348/17 $58.00+.00 © 2017 Bentham Science Publishers

570 Current Organic Chemistry, 2017, Vol. 21, No. 7 Kovács and Keglevich

ride [30], sodium aluminium hydride/sodium aluminium tetrachlo- of the double-bond also took place to afford species 8 (Scheme 4).
ride [31], and di-isobutylaluminium hydride [24, 32] have been Therefore, the incompatibility with double-bonds may be a draw-
employed for the deoxygenation of phosphine oxides [33, 34]. back of borane reductions.
Issleib and co-workers investigated the reduction of triphenyl-
Me Me Me Me Me Me
phosphine oxide (1) by LAH. It turned out that LAH was not too BH3
SMe2
efficient, as PPh3 was obtained in only a yield of 54% (Scheme 1) (5 equiv.)
[29, 35]. +
P CHCl3 P P
O 80 °C / 4 h O Ph H3B Ph H3B Ph
P LiAlH4 P 6 8 (73%,two isomers)
7 (27%)
Ph Ph Ph Ph
Ph Ph
Scheme 4.
1 2 (yield: 54%)
The same research team demonstrated that the reaction is de-
Scheme 1. pendent on the ring strain. While the reduction of the more strained
However, the application of additives, such as Lewis acids, led phosphine oxide with a five-membered ring (6) took place, there
to better conversions. The use of CeCl3 together with LAH resulted was no reaction with the six-ring phosphine oxide 9 (Scheme 5)
in a yield of 95% after a reaction time of 30 min at a temperature of [40, 41].
40 °C [30]. Imamoto observed that the LAH–CeCl3 system associ- Me 63 °C / 3 days Me
ated with NaBH4 allowed the one-pot preparation of phosphine BH3
SMe2
boranes from phosphine oxides (Scheme 2). Hence, the air sensitive
phosphines were stabilized as boranes [36, 37]. P P
CHCl3
O Ph H3B Ph
BH3
O 9 10
25 °C
P LiAlH4, NaBH4, CeCl3 P Scheme 5.
R1 R3 R1 R3
R2 THF R2 Pietrusiewicz and co-workers found that secondary phosphine
3 4 oxides (11) can be converted expeditiously to secondary phosphine
R1, R2, R3 = alkyl / aryl boranes (12) by treatment with an excess (3–10 equiv.) of
Scheme 2. BH3·SMe2 or BH3·THF at room temperature. The expected products
(12) were obtained in moderate to good yields (40–100%). In a few
Yang et al. studied the reduction of tertiary phosphine oxides cases, the formation of phosphinous acid–boranes (13) was also
with amine-assisted aluminum hydrides (Scheme 3). The method is observed, even in the presence of a large excess of the reducing
characterized by mild conditions, short reaction times, high effi- agent (Scheme 6).
ciency, and a wide substrate scope [38].
26 °C / 0.25
2 h
26 °C / 10 min BH3  THF BH3 BH3
O
H or
O H Al N P BH3  SMe2 P P
R1 H R1 H R1 OH
P H P THF
R1 R3 R1 R3 R2 R2 R2
hexane
R2 R2 11 R1, R2 = alkyl / aryl 12 13
3 R1, R2, R3 = alkyl / aryl 5
Scheme 6.
Scheme 3. Selectivity towards the formation of secondary phosphine
Aluminium hydrides are not appropriate for industrial applica- boranes could be greatly improved by the addition of a small
tion: they are expensive, highly reactive towards air and water, amount of water to the reaction mixture [42].
difficult to handle, and the reduction of an optically active The same authors extended their method to the reduction of
phosphine oxide may take place with racemization at the phospho- phosphine oxides with proximal
- or -hydroxy groups (14) using
rus center. BH3 under mild conditions (Scheme 7) [43].
The direct reduction of phosphine oxides by borane and borane BH3
complexes is also possible. It is convenient, and has the advantage O
of leading to stable and easy to handle phosphine-boranes. Köster P OH BH3 P OH
and Morita were the first who reported the use of borane derivatives R1 n
R1 n
as reducing agents to synthesize phosphines/phosphine–boranes R2 R2
R1, R2 = alkyl / aryl n = 1, 2
[39]. Triphenylphosphine oxide was deoxygenated with alkylbo-
14 15
ranes at a temperature of 120–180 °C. Keglevich and co-workers
reported the reduction of strained five-ring phosphine oxides with
Scheme 7.
borane–dimethyl sulfide complex under mild conditions [40]. The
reaction of 1-phenyl-3,4-dimethyl-3-phospholene oxide (6) with It was proved that the placement of a hydroxy group in the vi-
borane–dimethylsulfide at 25  65 °C in chloroform led to a mix- cinity of the P=O function resulted in an intramolecular activating
ture of products. Besides the expected deoxygenation and effect. The presence of a neighboring
- or -hydroxy group in the
phosphine–borane formation resulting product 7, partial reduction molecule is a key factor enabling the reduction. The lack of a
The Reduction of Tertiary Phosphine Oxides by Silanes Current Organic Chemistry, 2017, Vol. 21, No. 7 571

proximal hydroxy group, or its longer distance from the phosphorus Wittig reaction. The most common mean of the deoxygenation of
atom may cause unreactivity of the P=O bond toward BH3. phosphine oxides involves the application of silanes [25-28]. A
Lengthening the distance between the P=O bond and the OH group wide spectrum of silanes has been described as P=O deoxygenating
from
to  leads to a noticeable decrease in the reactivity of the agents. These days, it is a real challenge to accomplish the deoxy-
P=O group in reduction by BH3, and elevation of the reaction genation of phosphine oxides by cheap and user-friendly silanes,
temperature from room temperature to 60 °C, or even 80 °C is and to elaborate green chemical protocols. Within silanes, perhaps
required to promote the reduction [43]. trichlorosilane (Cl3SiH) is the most frequently used reagent in
Borane (used as different complexes) is much more user- synthetic organic chemistry [44, 53]. Fritzsche and co-workers
friendly than the metal hydrides are. However, the application of reported the first reduction of phosphine oxides by Cl3SiH in 1965
borane in P=O reductions is rather limited. [54]. Cl3SiH is rather volatile (bp.: 31.8 °C) and corrosive, hence it
Other reagents and combinations have also been developed is advisable to use it together with a tertiary amine. As one varia-
for the direct reduction of phosphine oxides. Calcium hydride CaH2 tion, the reduction of phosphine oxides with Cl3SiH was performed
[44], samarium iodide/hexamethylphosphoric triamide (SmI2/ in an autoclave at 200 °C in benzene in the presence of one equiva-
HMPA) [45], TiCp2Cl2/Mg [46], Bi/TiO2 [47], SiCl4 along with a lent of triethylamine (Table 1/Entry 1). It was observed that the
metal [48], sulfur derivatives [49] and hydrocarbons associated with need for 2 equivalents of Cl3SiH may be avoided by the addition of
activated carbon [50] have also been applied to reduction. However, an amine. In these cases, the use of 1.1 equivalents of Cl3SiH was
the procedures mentioned are not too attractive, since the reagents sufficient (Table 1/Entries 3–4). In the reduction of a cyclic
are rather expensive, or difficult to handle. Fritzche reported the phosphine oxide (2-phospholene oxide), Cl3SiH was not efficient
reduction of triphenylphosphine oxide (TPPO) with CaH2 at higher together with triethylamine, as the yield was only 24% (Table
temperatures (350–400 °C) giving rise to triphenylphosphine in 1/Entry 5) [55]. The group of Keglevich reported the reduction of
moderate to good yields (38–63%) [44]. Handa developed a method 3-phospholene oxides, phospholane oxides, and a 1,2,3,6-
for P=O deoxygenation using SmI2 in a large excess (22 equiv.) in tetrahydrophosphinine oxide with Cl3SiH–C6H5N in boiling toluene
hexamethylphosphoric triamide (HMPA) as the solvent. Triphenyl (Table 1/Entries 6–8). New platinum complexes of cis-Pt(L)2Cl2
phosphine was obtained in a yield of 75% after a prolonged reaction type have been synthesized from these five- and six-membered
time (Scheme 8) [45]. cyclic phosphines [15-18]. A phosphabicyclo[3.1.0]hexane 3-oxide
was also deoxygenated by Cl3SiH at 0 °C, and the phosphine
O 65 °C / 16 h so obtained reacted with dimethyl sulfide-borane to give the
SmI2 / THF
P P corresponding borane complex in a quantitative yield (Table
Ph Ph Ph Ph 1/Entry 9) [56]. Horner and Balzer reported the first study on the
Ph HMPA Ph
reduction of optically active phosphine oxides (Table 1/Entry 10)
1 2 (yield: 75%)
[57].
Scheme 8. In 1984, Quin described the reduction of a 1-amino-3-
phospholene oxide (6) using trichlorosilane-pyridine to afford even-
As a special method, the direct electroreduction of phosphine
tually chlorophospholene (7) formed after the fission of the P–N
oxides has been reported by Tanaka in the presence of trimethyl-
bond (Scheme 10) [55].
silyl chloride (Scheme 9) [51]. Electrochemical reduction that can
Me Me
be carried out under mild conditions, is a highly promising proce-
78 °C / 2 h
dure [52]. Cl3SiH
C6H5N
O plausible intermediate P PhH P
+ 2e
O NEt2 Cl
P P R1
R1 R3 R1 R3 6 7 (yield: 60%)
Me3SiCl R2 P O SiMe3
R2 R2
Bu4NBr Scheme 10.
3 MeCN 5 R3
It was observed that Cl3SiH is an especially useful reducing
R1, R2, R3 = alkyl / aryl agent in the synthesis of P-chiral phosphines, as in these cases, the
Scheme 9. phosphines may usually be obtained in high optical yields. The
stereochemistry of the deoxygenation may depend on how Cl3SiH
2.2. Deoxygenation of Phosphine Oxides by Silane Reagents is used. The application of Cl3SiH alone, Cl3SiH–pyridine or
Cl3SiH–N,N-diethylaniline resulted in retention of configuration at
2.2.1. Deoxygenation of Phosphine Oxides Using Trichlorosilane
the phosphorus center, but the use of Cl3SiH–NEt3 led to
The importance of the P=O  P transformation was discussed phosphines formed with inversion of configuration (Scheme 11).
in the Introduction referring, among others, to P-ligands and the This outcome was also supported by theoretical calculations [58].

inversion retention
O
P Cl3SiH
NEt3 P Cl3SiH P
R3 R1 R3 R1 R3
R1 Cl3SiH
C6H5N
R2 R2 R2
(
) ee = 93% (
) ee = 98% (+) ee = 82%
8 9 10

Scheme 11.
572 Current Organic Chemistry, 2017, Vol. 21, No. 7 Kovács and Keglevich

Table 1. Deoxygenation of different phosphine oxides to the corresponding phosphines by trichlorosilane.

Entry Starting Material Product Silane Equiv. Solvent T (°C) t (h) Yield (%) Ref.

1 Ph3P=O Ph3P Cl3SiH 2 – 200 2 90 [54]

2 Ph3P=O Ph3P Cl3SiH 2 PhH 78 2 98 [54]

a
3 Ph3P=O Ph3P Cl3SiH 1.1 PhH 78 2 85 [54]
a
4 (C4H9)3P=O (C4H9)3P Cl3SiH 1.1 PhH 80 2 92 [54]
Me Me

5 Cl3SiH a 1.1 PhH 78 2 24 [54]

P P
O Ph Ph
Me
Cl3SiH b 1.4 PhMe 110 2 91 [14]
Me
P
6 O R
R = Ph P Cl3SiH 5.9 PhH 0 3 total conversion [17,18]
R
R = Et, Pr, Bu,
iBu, iPent

Me Me

7 Cl3SiH b 1.4 PhMe 110 2 89 [15]

P P
O Ph Ph
Cl Cl
Me Me
8 Cl3SiH b 1.4 PhMe 110 2 96 [15,17]
P P
O Ph Ph
Cl Cl Cl Cl
Me Me
9 Cl3SiH 1.1 CH2Cl 2 0 6 95 [56]
P P
O Ph Ph

10 MePhBzP=O MePhBzP Cl3SiH a – PhH 180–190 2 69 [57]

a
1.1 equiv. of NEt3 was measured in.
b
3 equiv. of C6H5N was measured in.

Mechanistic studies were first reported by Horner and Balzer in species 14 with an inverted P-atom through an intermolecular (SN2)
1965 [57]. Three reaction pathways involving the reduction with hydride transfer (Scheme 13, Path A) [57]. Using pyridine, the in-
Cl3SiH (Scheme 12), Cl3SiH and Et3N, as well as with Cl3SiH and ternal hydride delivery is similar to that shown in Scheme 12
C6H5N (Scheme 13) were recommended. (Scheme 13, Path B) [59].
Using Cl3SiH alone (Scheme 12), the reduction of the P=O Mislow and co-workers assumed that the difference in basicity
moiety occurs through transition state 11 to afford intermediate 12 between triethylamine and pyridine influences the reactivity of the
that is stabilized by a proton transfer. The configuration at the P corresponding complexes. Strong bases give the phosphine with
atom is preserved. predominant inversion, while weak bases afford the phosphine
with predominant retention of configuration (Scheme 14) [60].
According to this theory, the Cl3SiH–NEt3 complex is dissociated,
Cl PH O
and reacts with the phosphine oxide to give phosphonium interme-
P O + H Si Cl Cl
Cl H Si Cl diate 16. Its pentavalent form 17 is transformed to another phos-
Cl phonium intermediate 18 that is stabilized by the loss of Cl3SiH via
11 species 19. As can be seen, the outcome is again inversion.
Krenske studied the mechanism of the reduction of trimethyl-
phosphine oxide with Cl3SiH by quantum mechanical calculations
Cl Cl
P + HO Si Cl P H + O Si Cl [58]. For the reductions of phosphine oxides by Cl3SiH, the calcula-
Cl Cl tions confirmed the mechanism proposed by Horner [57], in which
12 a hydride is transferred from silicon to phosphorus through a four-
centered front-side transition state.
Scheme 12.
Cremer and Chorvat developed a method using Cl3SiH alone, or
When triethylamine was used as the base, zwitterion 13 reacts in combination with NEt3 to reduce phosphetane oxides 20 (Scheme
with the Cl3SiH–NEt3 complex to form eventually phosphonium 15). Retention was observed for both the cis and trans phosphetane
The Reduction of Tertiary Phosphine Oxides by Silanes Current Organic Chemistry, 2017, Vol. 21, No. 7 573

R1
R2 P O + Et3N SiHCl3
R1
R3 Cl Cl R1 R2 Cl Cl Cl Cl
R1 Cl3SiH P R2
2
H P R + Et3N Si O Si H Path A
Et3N Si H P O SiHCl3 R3
NEt3 +
Cl R3 R3 Cl Cl
R1 "Cl3SiOH"
R2 P O SiHCl3 + Et3N 14
Inversion
R3 13

R1
R1 R1
pyridine R2 P O
R2 P O + H SiCl3 R2 P + "Cl3SiOH" Path B
R3 R3
R3 H SiCl3 Py
15 Retention

Scheme 13.

R1
R2 P O R1
R3 SiCl3 R2 P OH
Et3N + H SiCl3 Et3NH SiCl3

Et3N R3
16

HO
R1 SiCl3 R1 SiCl3 R1 SiCl3
Cl3Si OH + P R2 P R2 P R3 R2 P R3
R3
R3 R1 OH
R2 OH
19 18 17

Scheme 14.

oxides, when a mixture of Cl3SiH–NEt3 was used as the reagent The double reduction of BINAP dioxide (24) to BINAP (25)
[61]. was achieved using the electron-poor triphenylphosphine (2 equiv.)
together with an excess of Cl3SiH. The yield of diphosphine 25 was
R1 Me R Me
90% (Scheme 17).
Me Cl3SiH (1 equiv.) Me
R2 R
Et3N (1 equiv.)
O
Me P Ph Me P Ph R1 100 °C / 24 h R1
P P R1
Me O R1 Cl3SiH, Ph3P
Me
R2 R2
20 21 P PhMe / THF P
R1 = Me, R2 = H R2 R2
O
R1 = H, R2 = Me
24 25
Scheme 15.
R1 = 3,5
(CF3)2C6H3
This result was in contrast with those described for acyclic R2 = 3,5
(CH3)2C6H3
phosphines (see Scheme 11 above). The steric hindrance around the
P atom may prevent the attack of the hydride anion from the more Scheme 17.
crowded side.
In the absence of Cl3SiH, no formation of the diphosphine was
In 2004, Spencer’s group reported the reduction of chiral
observed. These results are consistent with the proposal that an
phosphine oxides using triphenylphosphine in addition to Cl3SiH.
oxygen transfer takes place between the phosphine oxide and the
The "electron-poor" phosphine used was suitable to capture the
phosphine under the influence of Cl3SiH [62].
oxygen atom of the phosphine oxide deriving from an "electron-
rich" phosphine (22) [62]. The reduction took place with retention Quin and co-workers studied the reduction of bridged
of configuration at the P atom (Scheme 16). P-heterocycles with P=O function using Cl3SiH. Most of the
reductions occurred with fragmentation (that is a retro McCormack-
80 °C / 3 h OCH3 like reaction) releasing cyclohexa-1,3-diene and phosphinite 28
O OCH3
Cl3SiH (Scheme 18). The ring strain in the pentacoordinated intermediate
P Ph3P (2 equiv.) P
H3C H3C 27 may be responsible for the phenomenon observed. The reactions
Ph PhMe / THF Ph performed in the presence of pyridine afforded the corresponding
phosphines exclusively. The Cl3SiH–pyridine complex does not act
22 23 as the hydride donor, and the mechanism of this reduction does not
involve a pentacoordinated intermediate [53].
Scheme 16.
574 Current Organic Chemistry, 2017, Vol. 21, No. 7 Kovács and Keglevich

R O O SiCl3
P Cl3SiH R P H
RPHOSiCl3 +
28
27 29
26 R = aryl or alkyl

Scheme 18.
OH OH

N 145 °C / 12 h N N
Cl
Cl3SiH, NEt3
PPh2 + PPh2
PPh2 o-xylene
O

30 31 32

Scheme 19.
O

D P Ph
H D Ph
Cl3SiH P P
Ph Ph Ph Ph D
+
D Ph D Ph Ph D
Fe Fe Fe

33 34 35

Scheme 20.

Huang and co-workers reported an interesting phosphine oxide Cl3SiH was efficiently used by Sinou and co-workers in the fi-
bearing a pendant hydroxyl group. Applying Cl3SiH–NEt3 as the nal step of the preparation of a perfluorocarbon-soluble triaryl-
reducing agent, the formation of the corresponding quaternary phosphine ligand. The reduction was performed in conventional
phosphonium salt (31) was observed as the major product (90%). solvents in a yield of 87% in the absence of triethylamine [66], and
The carbon–phosphorus bond may be formed by an intramolecular in a yield of 96%, when triethylamine was also measured in [67].
quaternization (Scheme 19) [63]. The reduction of triarylphosphine oxides by Cl3SiH in the presence
Fyfe and co-workers described the first example of a deoxy- of NEt3 can be assisted by microwave (MW) irradiation allowing a
genation with Cl3SiH under heterogeneous conditions [64]. The shorter reaction time of 10 min, and a yield of 83% [68].
phosphine oxides were immobilized on silica, and then reduced to Nief and Fischer applied Cl3SiH in the reduction of 1-
phosphines with good conversions. It was also reported that a simi- hydrophosphabenzene 1-oxide iron complexes (33) to afford phos-
lar reduction of a phosphine oxide immobilized on polystyrene phadienyl iron complex isomers 34 and 35 (Scheme 20) [69].
resin led to the corresponding phosphine in a quantitative yield As it was shown, Cl3SiH is a widely applied reducing agent to
[65]. prepare phosphines. It is better to use this corrosive and volatile

Table 2. Deoxygenation of different phosphine oxides to the corresponding phosphines by phenylsilanes.

Entry Starting Material Silane Equiv. T (°C) t (h) Yield (%)

a
1 P PhSiH3 0.7 26 97 [44]
O Ph
Me Me

2 PhSiH3 0.8 80 2 82 [44]

P
O Ph
O
3 Ph P Ph Ph3SiH 2 300 2 90 [44]
Ph
O
4 Ph P Ph Ph2SiH2 0.8 120 2 90 [44]
Ph
O
5 Ph P Ph PhSiH3 0.8 120 2 82 [44]
Ph
a
Not provided.
The Reduction of Tertiary Phosphine Oxides by Silanes Current Organic Chemistry, 2017, Vol. 21, No. 7 575

reagent together with pyridine or NEt3. The nature of the amine also found that the remote 3-methyl substituent on 1-phenylphospholane
has an impact on the stereochemistry of the reduction. oxide had a little influence. Six- and seven-membered phosphine
oxides were reduced rather slowly, with less than 20% conversion
2.2.2. Deoxygenation of Phosphine Oxides Using Phenylsilanes
after a 3h reaction time (Scheme 22) [71].
Fritzsche and co-workers reported the first reduction of
100 °C
phosphine oxides with phenylsilanes, such as PhSiH3, Ph2SiH2 and
Ph2SiH2
Ph3SiH in 1964 [44, 54]. All of them could be used without any 36 37
solvent. PhSiH3 was applied in the range of room temperature to dioxane
150 °C [44, 54], while Ph3SiH at 300 °C (Table 2) [44]. Obviously, Reactivity of phosphine oxides according to the ring moiety:
PhSiH3 is the best choice that may utilize three hydrogen atoms
during deoxygenation. However, PhSiH3 is rather expensive.
< << ~
Marsi also investigated the applicability of PhSiH3, and ob-
served complete retention of configuration during the reduction of Scheme 22.
five and six-membered ring phosphine oxides (36) to give the
phosphines (37) in yields of
85% (Scheme 21) [70]. Phenylsilane reduced selectively the P=O bonds of a bis secon-
dary phosphine oxide bearing two allyl groups (38). The resulting
80
100 °C bisalkylphosphine (39) underwent intramolecular hydrophosphina-
PhSiH3 (0.6 equiv.) tion to form eventually the corresponding bicyclic tertiary
P P
phosphine (41) (Scheme 23) [72].
O Y Y
36 37 (85-92%) Macrocyclic tetraphosphines (43) were prepared from the cor-
responding phosphine oxides (42) by reduction with phenylsilane
(Scheme 24) [73].
The deoxygenation with phenylsilane follows a similar protocol
Y Ph, Me Ph Ph than that with Cl3SiH. The classical reduction scheme was refined
Scheme 21. by Pietrusiewicz et al. utilizing Density Functional Theory (DFT)
calculations [74]. The first TS (44) afforded a covalent species (45).
Van Kalkeren investigated the effect of the ring size of cyclic A second TS (46) was also substantiated. It was proved that the
phosphine oxides (36) on the rate of the reduction by silanes, as model reaction between tri-butylphosphine oxide and phenylsilane
well as the influence of a 3-methyl substituent in the ring. It was occurs via a nonpolar mechanism (Scheme 25).

O O
PH PH PhSiH3 HP PH
HP P
P P

38 39 40 41

Scheme 23.

Ph Ph Ph Ph
P P 130 °C P P
O O PhSiH3 (13 equiv.)

O O neat
P P P P
Ph Ph Ph Ph

42 43

Scheme 24.
Bu
Bu H Bu P O Bu H H
Bu P O + H Si Ph H Bu P Si Ph
Bu H Si
H Ph Bu O H
Bu
H
prereaction complex 44

Bu H Bu Bu H H
H
Bu P + HO Si Ph Bu P H Bu P Si Ph
H Bu O Si Ph O H
Bu Bu
H
46 45

Scheme 25.
576 Current Organic Chemistry, 2017, Vol. 21, No. 7 Kovács and Keglevich

t-Bu t-Bu

N O N O

O 140 °C / 13 h
Ph2SiH2
F3C P CF3 F3C P CF3

F3C F3C
47 48 (yield: 86%)

Scheme 26.

Diphenylsilane was used to deoxygenate a triarylphosphine O 20 °C

oxide (47) bearing a chiral oxazolidine group (Scheme 26) [75]. Ph2SiH2 or PhSiH3 (4 equiv.) H
R1
P OEt R1 P
Unsaturated secondary phosphine oxides are important inter- B(C6F5)3 (3
5 mol%) H
OEt
mediates. The conventional method using phenylsilane can be toluene
applied well for the deoxygenation of secondary ethynylphosphine 51 52 (1)
R1 Yield (%)
oxides (49) to furnish the corresponding phosphines (50) in
Me 25
55–75% yields. In the last two instances, trichlorophenylsilane was
CH2Cl 95
also measured in (Scheme 27 and Table 3) [27, 76]. CHCl2 25
H 95
O 26
70 °C
silane
R1 P H R1 P O 20 °C
H Ph2SiH2 or PhSiH3 (4 equiv.) H
MeO(CH2CH2O)4Me P
R2 R2 R1 OEt R1 P
or B(C6F5)3 (3
5 mol%)
49 THF 50 R2 R2
toluene
53 54 (2)
R1 R2 Yield (%)
Scheme 27.
Me Et 85
Phosphonates (51) may be reducted to primary phosphines with CCl2Et menthyl 85
phenylsilane or diphenylsilane in the presence of 3–5 mol% of Bn CH=CH2 40
tris(pentafluorophenyl)borane. The reaction was generally slow at
Scheme 28.
room temperature. No change was observed at a higher tempera-
ture. The yields were generally better with phenylsilane, than with 2.2.3. Deoxygenation of Phosphine Oxides Using Miscellaneous
diphenylsilane (ca. 95% vs. 25%) (Scheme 28/(1)). However, the Silanes
formation of unidentified by-products could not be avoided. On the Alkyldichlorosilanes (RSiCl2H, where R = Me, Et, nPr, iPr, nBu,
n
other hand, the reduction of phosphinates (53) to secondary Hex) and phenyldichlorosilane (PhSiCl2H) are also potential re-
phosphines could be performed using only 4 equivalents of phenyl- ducing agents, but these reagents remained of limited use [77].
silanes (Scheme 28/(2)). It is easier to apply this method, than the It is interesting to note that perchlorosilanes (e.g. hexachloro-
one involving aluminum hydrides as the reducing agent. disilane (Si2Cl6)) were also described as reducing agents [78, 59].
From among phenylsilanes, PhSiH3 is the reagent of choice that The reduction of a chiral tertiary phosphine oxide (55) with Si2Cl6
is a robust reducing agent. An obvious drawback is the higher price took place with inversion of configuration (Scheme 29).
of this reagent.

Table 3. Deoxygenation of secondary phosphine oxides (49).

R1 R2 Silane Yield (%)

i
H Pr PhSiH3 65

H t-Bu PhSiH3 55
i
Ph Pr PhSiH3 70

Ph t-Bu PhSiH3 70

Ph Et PhSiH3 70

H Ph PhSiH3/PhSiCl3 75

Ph Ph PhSiH3/PhSiCl3 75
The Reduction of Tertiary Phosphine Oxides by Silanes Current Organic Chemistry, 2017, Vol. 21, No. 7 577

O 78 °C / 10 min O 110 °C / 24 h
P (EtO)2MeSiH (3 equiv.) P
P Si2Cl6 (1.4 equiv.) P
Bn Me Ph Ph Ph Ph
Bn Me 15 mol% catalyst Ph
benzene Ph Ph toluene
Ph
Cl3Si
O
SiCl3 (
) ee = 91%)
55 56 (yield: 70%) Scheme 32.
Table 5. Acid-catalyzed reduction of phosphine oxides.
Scheme 29.

However, the Si2Cl6 reduction of phosphetane oxides proceeded Entry Catalyst Yield (%)
with retention of configuration at phosphorus [79].
1 – <1
Gilheany and co-workers observed that the two diastereomers
of the P-chiral binaphthyl monophosphine oxides showed different 2 (PhO)2P(O)OH 75
reactivity and stereoselectivity in silane reductions. Moreover, the 3 (4-NO2C6H4O)2P(O)OH >99
reactivity also depended on the reaction time (Scheme 30 and Table
4). Si2Cl6 reduced diastereomer (57a) to give the corresponding 4 (4-CF3C6H4O)2 P(O)OH >99
phosphine (58a) with retention of configuration. In a sharp contrast, 5 Ph2P(O)OH 21
a mixture of Cl3SiH–NEt3 led to the phosphine (58b) with inversion
6 PhPO(OH)2 9
at the phosphorus centre [80].
7 PhCOOH 6

O R2 R2 No reaction took place without a catalyst (Table 5/Entry 1).

Using 15 mol % of benzoic acid, low yields of triphenylphosphine
P R1 reduction P R1
were obtained (Table 5/Entry 7). Surprisingly, the addition of the
OCH3 OCH3 diphenyl ester of phosphoric acid resulted in PPh3 in a yield of 75%
(Table 5/Entry 2). Furthermore, varying the electronic properties of
the P-acid catalysts by introducing an electron-withdrawing group,
57 58
such as NO2 or CF3 in the aryl ring, the deoxygenation became
R1 = Me, R2 = Ph (a) quantitative (Table 5/Entries 6, 7).
R1 = Ph, R2 = Me (b) Lawrence et al. used three equivalents of triethoxysilane, and a
catalytic amount of titanium(IV) isopropoxide to convert tertiary
Scheme 30.
phosphine oxides to the corresponding phosphines (Scheme 33 and
Quin devised a method for the preparation a 1-chlorophos- Table 6) [82, 84].
pholene (60) comprising the reduction of 1-chlorophospholene O 67 °C
oxide (59) with Si2Cl6 at room temperature (Scheme 31) [81]. (EtO)3SiH (3 equiv.) P
P Ph Ph
Ph Ph Ti(OiPr)4 (0.1 equiv.) R
Me R THF
Me
26 °C / 12 h
Si2Cl6 Scheme 33.

PhH P Table 6. Reductions with triethoxysilane.

P
Cl O
Cl
59 Entry R Yield (%)
60 (yield: 58%)
1 Ph 85
Scheme 31.
2 CH2CH 2P(O)Ph2 90
More user-friendly silanes are (EtO)3SiH [82], (EtO)2MeSiH 3 Me 99
[83], 1,1,3,3-tetramethyldisiloxane (TMDS), and
4 Et 95
polymethylhydrosiloxane (methylpolysiloxane [PMHS or MPS])
described by formula [–O–SiH(Me)–]n [44, 82, 83]. These silanes 5 i
Pr 81
are, however, not too reactive. i
6 Bu 41
Beller et al. studied the effect of different acids in the reduction
7 CH2Ph 98
of triphenylphosphine oxide with diethoxymethylsilane as the
reducing agent (Scheme 32 and Table 5) [83]. 8 CH2CH 2Ph 83

Table 4. Diastereoselectivity for the reduction of P-chiral binaphthyl monophosphine oxides.

P=O Silane Phosphine (58a) Phosphine (58b) Yield (%)

57a SiCl3-NEt3 50 50 65

57a Si2Cl 6 100 0 60

57b Si2Cl 6 30 70 70

57b Si2Cl 6 14 86 36
578 Current Organic Chemistry, 2017, Vol. 21, No. 7 Kovács and Keglevich

Table 7. The Reduction of triphenylphosphine oxide with TMDS in the presence of catalysts.

Equivalent Catalyst
Entry T (°C) t (h) Conv. (%) Ref.
of TMDS (mol %)

1 12 - 100 2 <1a [85]

a
2 3 Cu(OTf)2 (10) 100 15 96 [85]
a
3 3 (PhO)2P(O)OH (15) 110 24 62 [83]
i b
4 1.2 Ti(O Pr)4 (10) 100 24 86 [86, 87]
b
5 3 InBr3 (1) 100 18 >99 [88]
a
Determined by GC.
b
Determined by 31P NMR.

Table 8. The catalyst-free reduction of triphenylphosphine oxide with TMDS.

Entry Solvent Equiv. Mode of Heating T (°C) t (h) Conv. (%)a Ref.

1 1,4-xylene 5
175 48 53 [89]

2 - 2
175 24 92 [90]

3 - 2 MW 175 6 37 [90]

4 - 2 MW 200 6.5 100 [90]

a 31
Determined by P NMR.

The reduction may be carried out in tetrahydrofuran, and pro- microwave (MW) heating in toluene, or in the absence of any sol-
ceeds slowly at room temperature, but becomes quantitative after a vent at different temperatures. It was found that the deoxygenation
heating at 67 °C for one hour. When only one equivalent of silane with TMDS under MW and solvent-free conditions is an efficient
was used, the reaction remained incomplete; two equivalents or method and, as there is no need for any catalyst, means a green
more are needed to attain a complete conversion [82]. In another chemical approach (Table 8) [89, 90].
example, the use of triethoxysilane in the presence of titanium Lemaire and co-workers studied the deoxygenation of cyclic
tetraisopropoxide in benzene at reflux gave the corresponding aryl- phosphine oxides, such as 3-methyl-1-phenyl-2-phospholene oxide
diphenylphosphine in a yield of 90% after 30 min [84]. (61a) with TMDS using 1% of InBr3 catalyst at 100 °C in toluene
The use of triethoxysilane has the drawback that it is toxic [88]. Completion of the reduction required 40 h (Scheme 35 and
(causing blindness), and although it is commercially available, it is Table 9/Entry 1). The Keglevich group performed this reaction
not cheap. successfully at reflux in toluene for 8 h without the use of any cata-
The Beller group disclosed that copper(II) triflate catalyzed the lyst (Table 9/Entry 2) [91]. The same authors studied the reduction
reduction of the P=O group carried out with the inexpensive TMDS of 3-methyl-1-phenyl-3-phospholene 1-oxide (61b) under thermal
at 100 °C in toluene (Scheme 34 and Table 7/Entry 2) [85]. Apply- and MW-assisted conditions without the use of any solvent. The
ing a large excess (12 equiv.) of TMDS, no deoxygenation was reductions under discussion were complete after a shorter reaction
observed without the catalyst (Table 7/Entry 1). On the other hand, time of 5 and 3 h, respectively (Table 9/Entries 3 and 4) [89].
Beller et al. also described the diphenyl ester of phosphoric acid as
/ MW
a metal-free catalyst [83], the use of 15 mol% of this diester-acid TMDS
promoted the deoxygenation at 110 °C in toluene (Table 7/Entry 3).
P solvent P
Lemaire and co-workers applied TMDS in the reduction of secon-
O Ph Ph
dary and tertiary phosphine oxides in the presence of a catalytic
61 62
amount of Ti(OiPr)4 [86, 87]. Triphenylphosphine oxide was de-
oxygenated in high conversion using 10 mol% of Ti(OiPr)4 at 100
°C in toluene (Table 7/Entry 4). Later on, the Lemaire group re- =
ported the use of InBr3 as the catalyst for P=O-reductions [88]. The
deoxygenation could be achieved efficiently in the presence of 1% a b
of InBr3 as the catalyst at 100 °C in toluene (Table 7/Entry 5).
Scheme 35.
O T/t
P
Lemaire et al. also studied the deoxygenation of tetraphenyl-
P TMDS
Ph Ph Ph Ph bis(phosphine oxides) (63). Derivative 63 with n=3 could be re-
catalyst Ph
Ph toluene duced well, while in case of n=4 there was, surprisingly, no reac-
tion.
Scheme 34. It was assumed that the reason for the difference in the
The authors of this review investigated the deoxygenation of reactivity was caused by the different solubility of the bisphosphine
triphenylphosphine oxide with TMDS under conventional and oxides (Scheme 36) [88].
The Reduction of Tertiary Phosphine Oxides by Silanes Current Organic Chemistry, 2017, Vol. 21, No. 7 579

Table 9. Reduction of phospholene oxides with TMDS.

Entry P=O (61) Silane (equiv.) Catalyst (mol %) Solvent Mode of Heating T (°C) t (h) Conv. (%) Ref.

InBr3
1 a TMDS (3) PhMe
100 40 95a [88]
(1)

2 a TMDS (2) – PhMe
110 8 82b [91]

3 b TMDS (2) – –
110 5 100b [89]

4 b TMDS (2) – – MW 110 3 100b [89]

a
Determined by GC.
b
Determined by 31P NMR.

O O 100 °C / 24 h From among the "practical" reducing agents, PMHS was

TMDS described for the deoxygenation of triphenylphosphine oxide. At
P P P P
Ph Ph Ph Ph 290 °C and without the use of any solvent, triphenylphosphine was
n
InBr3
Ph Ph toluene Ph n Ph obtained in a yield of 88% (Table 10/Entry 1) [44]. Regarding the
64
63 application of PMHS, the relatively high temperature required is
n Yield (%)
not too attractive. Beller et al. observed that using a large quantity
3 99 (12 equiv.) of PMHS in toluene, practically no deoxygenation oc-
4 0
curred at 100 °C after 2 h (Table 10/Entry 2). However, using
Scheme 36. Cu(OTf)2 as the catalyst, the reduction of the P=O bond took place,
and at 100 °C after 15 h, the yield was 88% (Table 10/Entry 3) [85].
Investigating the mechanism of the deoxygenation with TMDS,
Measuring in 15 mol% of (PhO)2P(O)OH, the reduction was slower
Lemaire drew conclusions based on electron paramagnetic reso-
under the same conditions, and the phosphine (2) could be isolated
nance analysis and 29Si NMR. The main result of these studies is
in a yield of 35% after 24 h (Table 10/Entry 4) [83]. Lemaire and
the evidence for the presence of a Ti(III) intermediate, which may
co-workers developed a method for the deoxygenation of the P=O
be formed via a single electron transfer mechanism (Scheme 37)
bond in the presence of Ti(OiPr)4 in boiling THF (Table 10/Entry 5)
[86, 92].

Ph Ph
H H H Ph3P O P Ph
Si Si Si Si H O
O O
TiIV TiIII Si Si
O

PPh3

H OH H O
polymerization Si Si Si Si
H2O O O
TiIV TiIII

Scheme 37.
Table 10. The reduction of triphenylphosphine oxide with PMHS.

Catalyst
Entry Silane (equiv.) Mode of Heating Solvent T (°C) t (h) Yield (%) Ref.
(mol %)

1 PMHS (5) –
- 290 2 86a [44]

a
2 PMHS (12) –
PhMe 100 2 0 [85]
a
3 PMHS (6) Cu(OTf)2 (10)
PhMe 100 15 88 [85]
a
4 PMHS (4) (PhO)2P(O)OH (15)
PhMe 110 24 35 [83]
i b
5 PMHS (10) Ti(O Pr)4 (1)
THF 67 93 [82]
c
6 PMHS (5) –
1,4-xylene 175 48 85 [91, 93]

7 PMHS (2) –
– 175 17 87 [90]

8 PMHS (2) – MW – 175 8 90 [90]

a
Determined by GC.
b
Not provided.
c
Estimated conversion on the basis of 31P NMR.
580 Current Organic Chemistry, 2017, Vol. 21, No. 7 Kovács and Keglevich

[82]. Keglevich et al. applied PMHS at a higher temperature, with- approach is the corrosivity of Cl3SiH [94]. In order to eliminate the
out any catalyst, but under solvent-free thermal and MW-assisted problems outlined, a better method was developed applying more
conditions. The deoxygenation was complete at 175 °C after 17 h safe organic dichlorosilanes (YSiCl2H, Y = aryl, alkyl) (Scheme 39
on conventional heating (Table 10/Entry 7). In the MW variation, 8 and Table 12/Entries 1 and 2) [77].
h was enough to attain an almost quantitative conversion (Table
O
10/Entry 8). The comparative thermal reduction in xylene required X X
a reaction time of 48 h (Table 10/Entry 6) [93]. Ar1 P(Ar2)2 YSiCl2H Ar1 P(Ar2)2
Fritzsche reported the first reduction of phospholene 1-oxides Ar1 P(Ar2)2 xylene Ar1 P(Ar2)2
with PMHS [44]. It could be used well without any solvent at X X
250 °C (Table 11/Entries 1 and 3). Keglevich and Kovács O
accomplished these reactions successfully at reflux in toluene for 67 68
6 h (Table 11/Entries 2 and 4) [91]. The reduction of 3-methyl-1- Ar1, Ar2 = Ph, Naph
phenyl-3-phospholene 1-oxide (65c) was also studied under thermal X = alkylene
and MW-assisted conditions without the use of any solvent. These Y = aryl, alkyl
reductions were complete at 110 °C after 4 and 2 h, respectively
Scheme 39.
(Scheme 38) Table 11/Entries 5 and 6) [90].
Keglevich et al. studied the deoxygenation of 3-methyl-1-

/ MW
PMHS phenyl-3-phospholene 1-oxide and triphenylphosphine oxide using
a series of silanes comprising an aralkylsilane, arylsilanes, diarylsi-
P solvent P
lanes, a disiloxane, a polysiloxane and a disilane under solvent-free
O Ph Ph
65 66 thermal or MW-assisted conditions (Scheme 40) [90].

/ MW
R1 O R1 R1 Ph
silane (59-66)
P P Ph
= R2 Ph no solvent R2 R2 Ph

a b c 69 70
The silanes are shown below.
Scheme 38.
Scheme 40.
Lawrence investigated the reactivity of triethoxysilane and
PMHS in the presence of titanium(IV) catalyst in the reduction of On the basis of the experimental data, the following order of
phosphine oxides. A mechanism involving retention of configura- reactivity of the silanes was found:
tion was proposed for these reductions [82].
PhSiH3 ~ NaphSiH3 > BnSiH3 > (4-MePh)2SiH2 > P
TMDS and PMHS are user-friendly and cheap deoxygenating
71 72 73 74
agents. Their relatively lower reactivity can be overcome by a sol-
vent-free and MW-assisted accomplishment. > PMHS > (Ph2SiH)2 ~ TMDS > (1-napht) 2SiH2
75 76 77 78
One way of preparing bis(diarylalkylphosphines) (68) is the de-
oxygenation the corresponding bis(diarylalkylphosphine oxides) The arylsilanes (71 and 72) were somewhat more reactive than
(67) with trichlorosilane in a solvent. However, the yield of this BnSiH3 (73). This group of reactive silanes bearing three hydrogen
transformation was as low as 30%. The other disadvantage of this atoms is followed by those representatives bearing two hydrogen

Table 11. Reductions of phospholene oxides with PMHS.

Entry Phosphine oxide (65) Silane (equiv.) Mode of Heating Solvent T (°C) t (h) Yield (%) Ref.

1 a 5
- 250 2 88 [44]

2 a 2
PhMe 110 6 85 [91]

a
3 b 5
- 250 35 [44]

4 b 2
PhMe 110 6 92 [91]

5 c 2
- 110 4 91 [90]

6 c 2 MW - 110 2 92 [90]
a
Not provided.

Table 12. Reduction of bis(diarylalkyl)phosphine oxides (67) with organic dichlorosilanes.

Entry Silane (equiv.) Base (equiv.) Solvent T (°C) t (h) Yield (%) Ref.

1 MeCl2SiH (5) Bu3N (5) xylene ~140 12 97 [77]

2 PhCl2SiH (3) Bu3N (5.5) xylene ~140 13 95 [77]

The Reduction of Tertiary Phosphine Oxides by Silanes Current Organic Chemistry, 2017, Vol. 21, No. 7 581

100 °C / 24 h
Ph
P
O O (10 mol%)
O
Ph2SiH2 (1.1-1.5 equiv.)
C + Br C CO2Me
Ph H OMe Ph
Na2CO3, toluene
79 80 81

Scheme 41.

atoms, or only one proton per silicon moiety. Thus, the next is (4- Plietker et al. developed a catalytic Wittig reaction applying a
MePh)2SiH2 (74) that was followed by PMHS (75), and then by dual catalytic system comprising an iron hydride complex reductant
(Ph2SiH)2 (76) and TMDS (77). The least reactive silane in this (in a catalytic amount) along with a silane (used in stoichiometric
series was (1-napht)2SiH2 (78). Its low reactivity is obviously the quantity) to reduce the phosphine oxide formed from PPh3
consequence of steric hindrance. (measured in in a catalytic amount) [104].
2.2.4. In situ Phosphine Oxide Reductions as a Part of Catalytic Werner developed a MW-assisted CWR. The reaction time was
Cycles decreased to 2-3 h using 10 mol% of tributylphosphine as the cata-
lyst in the presence of phenylsilane as the reducing agent, and buty-
The well-known stoichiometric phosphine-promoted reactions,
lene oxide as a masked base in dioxane at 150 °C [105]. Other
such as Wittig-, Mitsunobu-, Staudinger- and Appel reaction are
examples were also reported, including the synthesis of trisubsti-
widely used in organic chemistry. Recently, a lot of efforts have
tuted olefins [106]. A CWR was also developed using 5 mol% of
been made to render these reactions catalytic in respect of the
2-phenylisophosphindoline 2-oxide as the catalyst [107], and an
phosphine. Besides decreasing the wastes, these catalytic reactions
enantioselective catalytic Wittig reaction was also elaborated [108].
have the advantage of facilitating the purification of the products.
Later on, a base-free Wittig reaction was also developed [109, 110].
The regeneration of the active catalyst was possible by means of a
Lin et al. described an efficient method using 3-aroyl acrylate
deoxygenating agent that reduces in situ the phosphine oxide
derivatives [111].
formed during the reaction. In accord with green chemical princi-
ples, the use of a catalytic amount of phosphine would be a great Last but not least, the “life cycle analysis” of the catalytic
development [95-97]. Wittig reaction has been studied by Hoiberg’s et al., and they calcu-
lated a decrease in the cumulative energy demand and greenhouse
O’Brien developed the first catalytic Wittig reaction applying
gas emissions, as compared to the Wittig reaction stoichiometric in
the phosphines in only catalytic amounts, and ensuring the deoxy-
respect of the phosphine [112].
genation of the phosphine oxide formed by the addition of one
equivalent of a silane [98]. After an optimization, 3-methyl-1- Van Delft et al. developed the first phosphine catalyzed
phenyl-phospholane oxide and Ph2SiH2 were found to be the most Staudinger reduction using a dibenzophosphole catalyst and PhSiH3
suitable reagents together with Na2CO3 as the base, using toluene as as the reducing agent [113]. They also introduced a catalytic
the solvent at 100°C. This kind of Catalytic Wittig Reaction (CWR) Staudinger/aza-Wittig reaction [114]. The azide reagent (84)
proved to be useful in the synthesis of different olefins. One exam- reacted first with 1-phenyl-dibenzophosphole (83) (measured in
ple is shown in Scheme 41. 10 mol%) via a Staudinger reaction to form instantly the
corresponding iminophosphorane species (85). The subsequent
Then, the same group performed the CWR using phenylsilanes
intramolecular aza-Wittig reaction delivered the corresponding
(most often PhSiH3 or Ph2SiH2) and other phosphine oxides
benzooxazole (86) and the phosphine oxide (82), which was
(including mainly phospholene- and phospholane derivatives, reduced in situ by the Ph2SiH2 or PhSiH3 present in the mixture
triphenylphosphine oxide and tri-n-octylphosphine oxide) [98-101]. (Scheme 42).
It was found that the cyclic phosphine oxides are reduced more
Ding reported the catalytic Staudinger/aza-Wittig reaction
readily, then their noncyclic analogues, or related derivatives (e.g.
for the synthesis of 4(3H)-quinazolinones using 5 mol% of
triphenylphosphine oxide). In these cases, the phosphoranes were
triphenylphosphine as the catalyst, and TMDS/Ti(OiPr)4 as the de-
formed in situ after the quaternization of the phosphine by the
oxygenating agent in toluene at reflux for 24 h. Isolated yields

-haloacetic ester [98-101], or even by a not too reactive alkyl
of 81-95% were reported [115].
halide [99]. The dehydrohalogenating agent was Na2CO3 [98, 100],
diisopropylethylamine [98], or in situ generated tBuONa [101]. To Herdewijn developed a phosphine catalyzed diaza-Wittig
be able to perform the reactions at room temperature, O’Brien reaction with the use phospholene oxide as the precursor of the
phosphine catalyst, together with diphenylsilane as the reductant in
suggested adding a Brønsted acid, such as p-nitrobenzoic acid into
toluene at 100 °C [116].
the mixture. According to the authors, this additive may have a dual
effect. On the one hand, it promoted the phosphine oxide reduction, Ashfeld et al. investigated a phosphine-catalyzed Staudinger-
while on the other hand, it could ensure a better solubility of the type ligation in the presence of PPh3 and PhSiH3 to convert
phosphonium salt intermediate [100]. carboxylic acids into amides [117].
The acyclic electron-rich phosphines, seem to be at first sight A dibenzophosphole catalyst together with Ph2SiH2 as the
the ideal species to catalyze these reactions, as they possess good reductant could be used well in a catalytic Appel reaction [71, 118].
nucleophilicity. However, it means a problem that the phosphine On the other hand, elaboration of the catalytic version of the
oxides under discussion cannot be reduced easily. For this, it is Mitsunobu reaction has also become a hot topic. In this reaction,
better to apply cyclic phosphines, such as phospholene- and PPh3, dibenzophophole and phospholane derivatives were often
phospholane oxides. Furthermore, silanes are selective reagents for used as catalyst together with suitable silanes [119-122]. The
reducing the phosphine oxides in the presence of functionalities, catalytic amide bond formation reaction between carboxylic acids
such as a carbonyl group or an unsaturation [89-93, 102, 103]. and amines was also developed using CCl4 (2.0 equiv.), 10 mol% of
582 Current Organic Chemistry, 2017, Vol. 21, No. 7 Kovács and Keglevich

Ph2SiH2
or
PhSiH3

P P
O Ph Ph
82 83
O O R
R Aza-Wittig Staudinger
O
N O R N3
86 84
O
N
P Ph

85

Scheme 42.
O Cl Cl
(COCl)2 P H2/Pd(PPh3)4 P
P
Ph Ph Ph Ph Ph Ph
Ph Ph Ph
87

Scheme 43.

O Cl BH3
26 °C / 0.5 h 26 °C / 1 h
(COCl)2 Cl NaBH4
P P P
R1 R3 toluene R1 R3 diglyme R1 R3
R2 R2 R2
88 89 (> 95% conversion)

Scheme 44.

PPh3 and (EtO)2MeSiH (1.5 equiv.)/(pNO2-C6H4O)2PO2H (5 The conversion of phosphine oxide to chlorophosphonium
mol%) as the reducing system [123]. chloride 88 may offer additional advantages beyond its easy reduc-
The catalytic protocol discussed above proved to be efficient in tion. It was also shown that phosphonium salt 88 could be con-
the other reactions, such as reduction of alkyl silyl peroxides [124] verted to the phosphine by the addition of LiAlH4 at low tempera-
or deoxygenative condensation of
-keto esters [125]. tures [135]. The group of Gilheany exploited the
insolubility of phosphonium salt 88 that makes possible its removal
3. REDUCTION OF PHOSPHINE OXIDES VIA CHLORO- from the reaction mixture after it was formed from the phosphine
PHOSPHONIUM SALT INTERMEDIATES oxide deriving from Appel and Wittig reactions. To this end, the
salt produced from the reaction of the phosphine oxide and oxalyl
In this case, the general scheme can be described by two main
chloride was separated by filtration. Interestingly, the use of alky-
steps: activation of the P=O bond by a suitable reagent (X–Y) to
lating reagents, such as methyl triflate or triethyloxonium
form a phosphonium or a radical intermediate followed by a
tetrafluoroborate (the Meerwein’s salt) in the first step afforded
hydride transport. The reducing reagents may be involved both as
alkoxy phosphonium salts (90), and after reduction phosphine bo-
an activator and the reductive agent itself. The transformation
ranes (91) stereoselectively with inversion of the P-configuration
starting with chlorination by oxalyl chloride is a widely studied
(Scheme 45) [136].
procedure [29, 126, 127]. The reduction of triphenyl-
dichlorophosphorane (87) obtained by the reaction of triphenyl- OR' BH3
O MeOTf or
phosphine oxide with (COCl)2 was performed by hydrogenation at (Et3O)BF4 X NaBH4
a high temperature and/or high pressure in the presence of transition P P P
Ph R Ph R diglyme R R
metal (Pt, Pd, Rh) catalysts (Scheme 43) [128, 129].
R R Ph
This reduction has also been reported in the presence of
90 91 (62
76%)
different metals, such as sodium, aluminium and iron, or applying
silicon [130-133]. Unfortunately, these procedures are not efficient
Scheme 45.
and not easy to perform. Rajendran and Gilheany developed a
one-pot transformation [134] involving the treatment of various In summary the possibilities for the deoxygenation of
secondary and tertiary phosphine oxides with oxalyl chloride in phosphine oxides to phosphines were surveyed. The phosphines are
toluene, followed by reduction with NaBH4 in diglyme to form the important as may be versatile reagents and ligands in transition
corresponding phosphine boranes (89) in good yields (Scheme 44). metal complexes. These days, the catalytic Wittig-, Mitsunobu- and
The Reduction of Tertiary Phosphine Oxides by Silanes Current Organic Chemistry, 2017, Vol. 21, No. 7 583

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