Organocatalyzed Reduction of Tertiary Phosphine Oxides

Article abstract of DOI:10.1002/adsc.201500762

A novel selective catalytic reduction method of tertiary phosphine oxides to the corresponding phosphines has been developed. Notably, the reaction proceeds smoothly with low catalyst loadings of 1-5 mol% even at low temperature (70 C). Under the optimized conditions various phosphine oxides could be selectively reduced and the desired phosphines were usually obtained in excellent yields above 90%. Furthermore, we have developed a one-pot reaction sequence for the preparation of valuable phosphinborane adducts. Simple addition of BH₃THF subsequent to the reduction step gave the desired adducts in yields up to 99%.

Full text of DOI:10.1002/adsc.201500762

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DOI: 10.1002/adsc.201500762
Organocatalyzed Reduction of Tertiary Phosphine Oxides
Marie-Luis Schirmer,a Stefan Jopp,a Jens Holz,a Anke Spannenberg,a
and Thomas Wernera,*
a
Leibniz-Institut für Katalyse e.V. an der Universität Rostock, Albert-Einstein-Str. 29a, 18059 Rostock, Germany
E-mail: thomas.werner@catalysis.de
Received: August 13, 2015; Revised: September 29, 2015; Published online: December 9, 2015
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201500762.
Abstract: A novel selective catalytic reduction
method of tertiary phosphine oxides to the corre-
sponding phosphines has been developed. Notably,
the reaction proceeds smoothly with low catalyst
loadings of 1–5 mol% even at low temperature
(708C). Under the optimized conditions various
phosphine oxides could be selectively reduced and
the desired phosphines were usually obtained in ex-
cellent yields above 90%. Furthermore, we have de-
veloped a one-pot reaction sequence for the prepa-
ration of valuable phosphine·borane adducts.
Simple addition of BH3·THF subsequent to the re-
duction step gave the desired adducts in yields up
to 99%.
task.[6] Although many catalytic procedures for the re-
duction of carbonyl groups have been established
over the past decades only little work is known on the
catalytic reduction of the thermodynamically highly
stable P=O bond.[6,7]
In 1994 Lawrence et al. developed the first catalytic
P=O reduction based on titanium alkoxides utilizing
silanes as stoichiometric reductants.[8] In fact, this was
the only catalytic method for the selective reduction
of phosphine oxides for almost two decades. Only re-
cently diarylphosphoric acid,[9] copper[10] and
indium[11] salts as well as iron[12] complex-catalyzed
processes have been reported. However, these meth-
ods usually require high catalyst loadings, harsh reac-
tion conditions and/or long reaction times. Based on
our interest on redox P(III)/P(V)=O catalysis our aim
was to develop a metal-free catalytic process operat-
ing at reaction temperatures <1008C and low catalyst
loading which might be suitable in such redox coupled
processes.[13] In this context we considered Brønsted
acids to be promising candidates to realize this
Keywords: organocatalysis; phosphine·boranes;
phosphines; reduction; silanes
Phosphines and their derivatives are of significant task.[9,13g,14]
relevance in life science and the chemical industry.
Thus, we initially screened various organic acids as
Especially trivalent phosphines are an essential class potential metal-free catalysts for the reduction of tri-
of compounds in organometallic catalysis and numer- phenylphosphine oxide (1a, Table 1). Under the
ous fundamental organic transformations. They repre- chosen reaction conditions no conversion was ob-
sent a ubiquitous family of ligands to control the served in the absence of a catalyst (entry 1). Benzoic
chemo-, regio- as well as stereoselectivity of most acid (3a) as well as derivative 3b gave the desired re-
transition metal-catalyzed reactions even on the in- duction product 2a in low yields of only 4% and 8%,
dustrial scale.[1] Furthermore, phosphines are utilized respectively (entries 2 and 3). In contrast diphenyl-
in important classic transformations, such as the phosphoric acid (3c) gave 2a in moderate yield of
Wittig,[2] Appel[3] or Mitsunobu reactions,[4] ultimately 64% (entry 4). Remarkably, in the presence of tri-
yielding the corresponding oxides as undesirable by- fluoromethanesulfonic acid (3d) as the catalyst 2a was
products. Most recently, several methods have obtained in quantitative yield already after 1 h at
emerged addressing this issue by in situ regeneration 1008C (entry 5). Even at 708C the desired phosphine
of the phosphorus reagent leading to novel phospho- 2a was obtained in 62% yield after 1 h (entry 6). Ex-
rus-catalyzed reactions to bypass the phosphine oxide tension of the reaction time to 24 h allowed us to
waste.[5] Even though the reduction of phosphine reduce the catalyst loading to 1 mol% still giving an
oxides is the simplest and one of the major methods excellent 89% yield of 2a (entry 7). Furthermore, we
for the synthesis of phosphines, the selective reduc- evaluated various silanes as alternative reductants.
tion of the strong P=O bond or its conversion into the Under the optimized reaction conditions conversion
corresponding phosphine·boranes is still a challenging of triphenylphosphine oxide (1a) was achieved within
26
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Organocatalyzed Reduction of Tertiary Phosphine Oxides
Table 1. Reduction of triphenylphosphine oxide (1a) in the
presence of various Brønsted acids 3 as catalysts and reac-
tion optimization.[a]
Table 2. Scope for the acid-catalyzed reduction of phosphine
oxides 1 under mild conditions and one-pot conversion into
stable borane adducts 4.[a]
Entry
Substrate
mol%
Cat.
2
4
[%][b]
[%][c]
1
1a
1b
1
95
86
2
3
4
5
6
7
8
9
1
5
1
5
71
–
93
–
95
–
59
–
–
ꢀ99
1c
1d
1e
31
99
69
77
1
5[d]
1
Entry Cat. mol% Silane
Equiv. Temp. Time 2a
[8C]
[h]
[%][b]
ꢀ99
5[d]
91[e]
1
2
3
4
5
6
7
8
–
3a
3b 15
3c 15
3d 15
3d 15
–
15
PhSiH3 4.0
PhSiH3 4.0
PhSiH3 4.0
PhSiH3 4.0
PhSiH3 4.0
PhSiH3 4.0
PhSiH3 4.0
HexSiH3 3.0
100
100
100
100
100
70
1
1
1
1
1
1
24
24
0
4
8
64[c]
>99
62
89
95
10
11
1f
1g
5
5
77 (ꢀ99)[f]
ꢀ99
–
3d
3d
1
1
70
70
85
[a]
Reaction conditions: 1a (1.0 equiv.), cat. (1–15 mol%),
silane (3.0–4.0 equiv.), toluene, 70–1008C, 1–24 h.
Yield determined by 31P NMR.
Yield determined by GC methods using n-hexadecane as
internal standard.
[b]
[c]
12
13
1h
1i
5
5
94
84
99
ꢀ99
24 h at 708C and triphenylphosphine (2a) was ob-
tained in 95% yield (entry 8).
14
1j
5
92
92
With CF3SO3H as a highly active reduction catalyst
under mild reaction conditions in hand, we evaluated
the substrate scope. Since organophosphines 2 are
often prone to oxidation we envisioned to isolate
them as the corresponding stable borane adducts 4.
Such adducts have attracted increasing attention as
versatile building blocks, hydrogen storage materials
and ligands as well as stable phosphine precursors.[15]
We envisioned a one-pot, two-step reaction process
for the synthesis of 4 (Scheme 1).
Thus, triphenylphosphine oxide (1a) was reduced to
2a and directly converted to 4a by subsequent addi-
tion of BH3·THF to the reaction mixture (Table 2,
entry 1). The reduction of diaryl derivatives 1b and 1c
in the presence of 1 mol% catalyst gave the desired
phosphine oxides 2b and 2c only in moderate to good
yields, respectively (entries 2 and 4). However, if the
catalyst amount is increased to 5 mol% the desired
15
16
1k
1l
5
5
ꢀ99
ꢀ99
96
94
17
18
19
1m
1n
1o
5
5
5
96
90
ꢀ99
ꢀ99
ꢀ99
95
20
1p 10[g]
ꢀ99 (96)[e]
–
21
22
1q 10[h]
1r 10[h]
–
–
72
65
Scheme 1. Catalytic reduction of phosphine oxides 1 to the
corresponding phosphines 2 and subsequent conversion with
BH3·THF into stable complexes 4.
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Marie-Luis Schirmer et al.
Table 2. (Continued)
Entry
Substrate
mol%
Cat.
2
4
[%][b]
[%][c]
23
1s[i]
5
ꢀ99
75[j]
[a]
Reaction conditions: (i) phosphine oxide 1 (1 equiv.),
CF3SO3H (5 mol%), HexSiH3 (3.0 equiv.), toluene, 708C,
24 h; (ii) BH3·THF (2 equiv., 1M in THF), 238C, 2 h.
Yield determined by 31P NMR.
Isolated yields for the one-pot procedure.
1008C, 6 h.
Isolated yield.
48 h.
CF3SO3H (10 mol%), HexSiH3 (6.0 equiv.), dioxane.
CF3SO3H (10 mol%), HexSiH3 (6.0 equiv.), toluene.
90% ee.
[b]
[c]
[d]
[e]
[f]
Figure 1. ORTEP diagrams of the products 4l (left) and 4n
(right), ellipsoids drawn at 30% probability[17] (see the Sup-
porting Information for crystallographic data).
[g]
[h]
[i]
yield (entry 20). Notably, oxidized dppe [1,2-bis(di-
phenylphosphino)ethane] 1q could not be reduced
under our conditions (entry 21). In contrast the dppp
[j]
4s was obtained as a racemate.
phosphines 2b and 2c were obtained in excellent [1,3-bis(diphenylphosphino)propane] derivative 1r
yields of up to ꢀ99% which could be directly con- could be reduced to the bisphosphine 2r and further
verted to the corresponding borane adducts 4b and 4c converted the borane adduct 4r which was obtained
(entries 3 and 5). Unsaturated phosphine oxides 1d in 65% yield (entry 22). Finally the P-chiral phos-
and 1e could also be selectively reduced in good to phine oxide S-1s was converted under our standard
excellent yields (entries 6–9). Notably, 1e has been reaction conditions. Full conversion to the respective
utilized for example, by Marsden et al., as a catalyst phosphine 2s was achieved which was further reacted
for aza-Wittig reactions. It is also the precursor for to the borane adduct 4s. Unfortunately the reaction
a Wittig reaction catalyst.[5a,16] We reported that does not proceed stereospecifically and 4a was isolat-
2-phenylisophosphindoline 2-oxide (1f) is an efficient ed in 75% yield as racemate (entry 23). In a first at-
pre-catalyst for the Wittig reaction.[13d] The reduction tempt to extend the scope of our protocol to the con-
of 1f gave the desired phosphine 2f in 77% yield after version of secondary phosphine oxides we studied the
24 and in ꢀ99% after 48 h.
reduction of diphenylphosphine oxide under our stan-
However, the one-pot conversion of 1e and 1f to dard reaction conditions. Diphenylphosphine was ob-
their BH3 adducts was not possible. The conversion to tained in 62% yield. Subsequent conversion to the
the respective adducts was not complete and partial borane adduct gave a 1:1 mixture of the desired
decomposition back to the phosphine occurred upon borane adduct and diphenylphosphine oxide. This
chromatography of 4e. In contrast oxides 1g–1i could might be explained by partial reoxidation that oc-
be easily reduced and the corresponding products 2g– curred during the work-up.
2i obtained in yields >90% which could in turn be di-
rectly transformed into the stable products 4g–4i (en-
tries 11–13). We then turned our attention to the re- Conclusions
duction of aryl derivatives 1j–1o (entries 14–19). Usu-
ally the corresponding phosphines 2 could be ob- In conclusion, we have report a general method for
tained in excellent yields up to 99% and converted to the efficient reduction of phosphine oxides under
the corresponding borane adducts 4j–4o which were very mild conditions (708C) utilizing readily available
isolated in 90–99% yield. Notably, the ester function- trifluoromethanesulfonic acid as an organocatalyst
ality in 1k remained untouched (entry 15). Further- and hexylsilane as the reducing agent. The scope of
more, the products 4l and 4n could be obtained as col- the reaction has been evaluated and 18 phosphine
orless crystals suitable for X-ray crystallographic anal- oxides were reduced under the optimized conditions
ysis (Figure 1).[17]
to the corresponding phosphines in up to 99% yield.
Having demonstrated the successful reduction of Importantly, excellent chemoselectivity was observed
various monophosphine oxides, we finally applied our even in the presence of other reducible groups such
methodology to the preparation of bisphosphine 2p. as olefins and esters. Thus, this methodology might be
In the presence of 10 mol% CF3SO3H as the catalyst, applicable in catalytic processes based on the P(III)/
oxide 1p could be converted to 2p in an excellent P(V)=O redox couple such as catalytic Wittig and
28
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Adv. Synth. Catal. 2016, 358, 26 – 29

COMMUNICATIONS
Organocatalyzed Reduction of Tertiary Phosphine Oxides
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the direct access to the respective borane adducts in
a one-pot, two-step reaction sequence by simply
adding BH3·THF subsequent to the reduction. These
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In
a vial flushed with argon the phosphine oxide
1 (0.36 mmol) was added to a solution of CF3SO3H (1–
5 mol%) in toluene (1.2 mL). The reaction mixture was
stirred for 5 min at 238C. Subsequently, HexSiH3 was added,
the vial was flushed with argon, sealed and the reaction mix-
ture was stirred for 24 h at 708C to afford 2. The vial was
cooled to 238C, BH3·THF (2.0 equiv., 1M in THF) was
added and the reaction mixture was stirring for further 2 h
under argon at 238C. The crude product was purified by
column chromatography on silica gel (SiO2) with petroleum
ether (PE, 40–608C)/diethyl ether (Et2O) as eluents. After
removal of all volatiles under vacuum the desired product 4
was obtained.
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Synthesis of Triphenylphosphine·Borane (4a)[18]
According to the general procedure, CF3SO3H (2.7 mg,
0.018 mmol), triphenylphosphine oxide (1a, 100 mg,
0.359 mmol) and HexSiH3 (128 mg, 1.10 mmol) in toluene
(1.2 mL) were converted. After work-up 4a was obtained as
colorless crystals; yield: 85.5 mg (0.310 mmol, 86%). Rf
1
(SiO2, CH:EtOAc=2:1); 0.68; H NMR (300 MHz, CDCl3,
228C): d=0.61–1.85 (m, 3H), 7.39–7.67 (m, 15H);
13C{1H} NMR (75 MHz, CDCl3, 238C): d=128.91 (d, JC,P
=
3
1
10.2 Hz, 3”2CH), 129.30 (d, JC,P =58.0 Hz, 3C), 131.39 (d,
4JC,P =2.4 Hz, 3CH), 133.33 (d, 2JC,P =9.7 Hz, 3”2CH);
31P NMR (121 MHz, CDCl3, 228C): d=21.11 (m); 11B NMR
(96 MHz, CDCl3, 228C): d=À37.82 (dq); MS (EI, 70 eV):
m/z (%)=263 (19) [M+ÀBH3 +H], 262 (100) [M+ÀBH3],
261 (19), 184 (16), 183 (81), 152 (12), 108 (25), 107 (16);
HR-MS (ESI): m/z=299.1136, calcd. for C18H18BPNa [M+ +
Na]: 299.1135.
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[17] CCDC 1408783 (4l) and CCDC 1408784 (4n) contain
the supplementary crystallographic data for this paper.
These data can be obtained free of charge from The
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