An efficient base-catalyzed double addition of H-phosphine oxides to alkynes

Article abstract of DOI:10.1016/j.tetlet.2016.06.079

An efficient base-catalyzed double addition of H-phosphine oxides to alkynes is developed. In the presence of a catalytic amount of a base, the addition of various H-phosphine oxides to both aromatic and aliphatic alkynes took place efficiently to produce the corresponding bisphosphoryl compounds in excellent yields. This method provides an easy direct way to prepare bisphosphine oxides that are of high importance in organic synthesis.

Full text of DOI:10.1016/j.tetlet.2016.06.079

Accepted Manuscript
An efficient base-catalyzed double addition of H-phosphine oxides to alkynes
Aya Yoshimura, Yuta Saga, Yuki Sato, Akiya Ogawa, Tieqiao Chen, Li-Biao
Han
PII:
S0040-4039(16)30748-1
DOI:
http://dx.doi.org/10.1016/j.tetlet.2016.06.079
TETL 47806
Reference:
To appear in:
Tetrahedron Letters
Received Date:
Revised Date:
Accepted Date:
10 May 2016
15 June 2016
17 June 2016
Please cite this article as: Yoshimura, A., Saga, Y., Sato, Y., Ogawa, A., Chen, T., Han, L-B., An efficient base-
catalyzed double addition of H-phosphine oxides to alkynes, Tetrahedron Letters (2016), doi: http://dx.doi.org/
1
0.1016/j.tetlet.2016.06.079
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Aya Yohimura, Yuta Saga, Yuki Sato, Akiya Ogawa, Tieqiao Chen, and Li-Biao Han

1
Tetrahedron Letters
An efficient base-catalyzed double addition of H-phosphine oxides to alkynes
a
b
c
c
a
a,
Aya Yoshimura , Yuta Saga , Yuki Sato , Akiya Ogawa , Tieqiao Chen , and Li-Biao Han 
a
National Institute of Advanced Industrial Science and Technology (AIST), 1-1-1, Higashi, Tsukuba, Ibaraki, 305-8565, Japan.
Katayama Chemical Industries Co., Ltd, 26-22, 3-Chome, Higasinaniwa-cho, Amagasaki, Hyogo 660-0892, Japan
Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, 1-1 Gakuen-cho, Nakaku, Sakai, Osaka 599-8531, Japan
b
c
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
An efficient base-catalyzed double addition of H-phosphine oxides to alkynes is developed. In
the presence of a catalytic amount of a base, the addition of various H-phosphine oxides to both
aromatic and aliphatic alkynes took place efficiently to produce the corresponding bisphosphoryl
compounds in excellent yields. This method provides an easy direct way to prepare
bisphosphine oxides that are of high importnace in organic synthesis.
Available online
2
015 Elsevier Ltd. All rights reserved.
Keywords:
Base-catalysis;
Double addition;
Alkynes;
H-phosphine oxides.
Transition metal-free
Organophosphorous compounds are of importance in organic
synthesis, biochemistry and material sciences. The addition of a
organophosphorus compounds to functional materials. Literature
searches came across an early Russian report that double
additions of H-phosphine oxides to alkynes could take place in a
1
P-H bond to an unsaturated carbon-carbon bonds is one of the
most direct and atomic-efficient ways for the preparation of these
compounds. Recently, such additions catalyzed by a transition-
9a,11
KOH-DMSO “super basic media” 1.
This is an interesting
paper since it can prepare compound 1 from the readily
accessible materials without using a precious metal catalyst.
Indeed, using this method, we could prepare the corresponding 1
2
metal catalyst are being extensively studied.
2
by the addition of Ph P(O)H to simple alkynes such as
phenylacetylene and 1-octyne. However, limitations of this
method are evident. For example, since this reaction was carried
out in a hot “super basic media” KOH-DMSO, an alkyne with a
functional group (carbonyl or ester group, for example), that can
be damaged under such harsh basic conditions, is not applicable.
Scheme 1 Preparation of 1,2-bisphosphorylethanes 1.
Bisphosphoryl compound 1 is a useful type of molecules
because it can be easily reduced to the corresponding trivalent
bisphosphinoethanes which are highly useful phosphine ligands
3
for transition metal complexes. Compound 1 is also a useful
4
extractant for selective metal extractions and a potentially
5
effective flame retardant because of its high phosphorus-content.
In the literatures, compound 1 was prepared by the addition of
6
Ph
1
2
P(O)H to a vinylphosphine oxide, substitution reaction with
7
8
9
,2-dichloroethane, nucleophilic addition to ethylene oxide etc
(Scheme 1). Lin reported that the palladium-complex mediated
double addition of P(O)-H bonds to alkynes could also produce
the corresponding bisphosphoryl compounds under toluene-
reflux conditions.
10
Scheme 2 A possible mechanism for a base-catalyzed double
addition of Ph P(O)H to an alkyne.
2
We need a more convenient and economical way for the
preparation of 1 in our on-going study on the applications of
—
——

Corresponding author. Tel.: +81-29-861-4855; fax: +81-29-861-6344; e-mail: libiao-han@aist.go.jp

2
Carefully analyzing the possible mechanism of the Russian`s
work (Scheme 2), we considered that the large amount of a base
perhaps may be not necessary in this reaction since a) the base is
adducts in good yields (entries 2 and 3). 4-ethynylaniline was
1
2
also diphosphorylated and the expected adduct 1h was obtained
in 60% yield under the base-catalyzed conditions (entry 4).
Chloro group was tolerable well to give the product facilitating
further functionalization (entries 5 and 6).
2
only used to deprotonate Ph P(O)H to generate a phosphoryl
anion A, and b) once A is generated, a catalytic cycle should
work to generate 1, i.e. a catalytic amount of base should mediate
the addition! This indeed is the case. Herein we report our
modification of the Russian work that the double phosphorylation
of a variety of alkynes with secondary phosphine oxides can
efficiently take place under mild conditions in the presence of a
catalytic amount of bases (eq 1). A variety of H-phosphine
oxides could add to both aromatic and aliphatic alkynes,
producing the corresponding 1,2-bisphosphoryl compounds in
excellent yields. The highly catalytic efficiency and water-
solubility of the base catalyst also greatly facilitated the
purification process of the products since simple washing the
reaction mixture with water could get the products. This new
base-catalytic reaction provided an easy access to 1,2-
bisphosphoryl compounds.
Table 1. The base-catalyzed double addition of H-phosphine
a
oxide to phenylacetylene.
31
entry
phosphine oxide
product
P NMR
yield
>99%
90%
64%
isolated
yield
93%
76%
70%
b
1
2
3
4
Ph
(p-MeOC
(p-CF
Cy
(PhC H ) P(O)H
2
P(O)H
1a
1b
1c
1d
1e
6
H4)2P(O)H
3
C
6
H4)2P(O)H
2
P(O)H
>99%
73%
92%
62%
c
5
4
8 2
a
Reaction conditions: 0.1 mmol phenylacetylene, 0.2 mmol H-phosphine
o
oxides, 5 mol% t-BuOLi, 0.15 mL THF, 70 C, 4 h.
c
1
6 h
An electron-deficient alkyne with a CF
ring also produced the corresponding product 1k quantitatively
entry 7). However only 48% yield of 1l was obtained from the
3
group at the benzene
(
base-catalyzed reaction of 1-(4-ethynylphenyl)ethan-1-one with
As shown in Scheme 3, a mixture of phenylacetylene and 2
equiv of diphenylphosphine oxide in THF was heated at 70 C for
h in the presence of 5 mol% t-BuOLi (based on H-phosphine
o
Table 2. Base-catalyzed double addition of diphenyl phosphine
a
oxide to alkynes.
4
oxide), the bisphosphorylated product 1a was produced
quantitatively (entry 1). After purification by preparative GPC
using CHCl as eluent, a NMR spectroscopically pure 1a was
3
afforded in 93% isolated yield. The reaction also proceeded at
room temperature to give 52% yield of 1a (entry 2). t-BuONa
and t-BuOK could also catalyze this reaction efficiently (entries 3
entry
alkyne
product
isolated yield
93%
b
1
1a
and 4); however, when a weak base such as K
2 3 3
CO and NaHCO
2
3
4
5
1f
1g
1h
1i
88%
90%
60%
90%
was used as a catalyst, no reaction took places under similar
12
reaction conditions (entries 5 and 6).
6
1j
93%
7
8
1k
1l
85%
48%
Scheme 3 A base-catalyzed double addition of diphenyl
phosphine oxide to phenylacetylene. Yields were calculated by
3
1
P NMR spectra.
9
1m
1n
75%
87%
This base-catalyzed double addition is applicable to other H-
phosphine oxides (Table 1). Thus, in addition to diphenyl
phosphine oxide, di(4-methoxy)phenyl phosphine oxide also
reacted with phenylacetylene to produce the corresponding
product 1b in good yield (entry 2). A substrate bearing an
c
10
electron-withdrawing CF
3
group could also be converted to the
11
1o
82%
expected adduct 1c under the reaction conditions (entry 3).
Aliphatic H-phosphine oxides also served well. For example,
dicyclohexyl phosphine oxide added to phenylacetylene readily,
producing the expected product 1d quantitatively under similar
c
1
1
2
3
1p
1q
81%
87%
c
c
reaction conditions (entry 4). (PhC
2% isolated yield (entry 5).
4 8
H )
2
P(O)H also gave 1e in
14
1r
88%
6
c
1
5
1s
58%
Noticeably, both aromatic and aliphatic alkynes are applicable
to this reaction. As shown in Table 2, a variety of alkynes were
double-phosphorylated by diphenyl phosphine oxide under the
reaction conditions, producing the corresponding bisphosphoryl
compounds 1. Thus, phenylacetylene derivatives with electron-
donating groups such as methyl and methoxyl at the benzene ring
reacted with diphenyl phosphine oxide to give the expected
a
Reaction conditions: 0.1 mmol alkynes, 0.2 mmol diphenyl phosphine
o
oxide, 5 mol% t-BuOLi, 0.15 mL THF, 70 C, 15 h.
b
4
h.
c
0
.3 mmol Ph P(O)H, 20 h.
2

3
diphenyl phosphine oxide because of a competitive addition of
P(O)-H bond to the carbonyl group (entry 8). Heteroaromatic
alkyne, as exemplified by 2-ethynylpiridine, could also be double
phosphorylated with diphenylphosphine oxide, affording the
adduct 1m in 75% yield (entry 9). Other aromatic alkynes like 1-
ethynyl-2,4,5-trimethylbenzene and 1-ethynylnaphtalene also
served as good substrates (entries 10 and 11). The
diphosphorylation of aliphatic alkynes were also achieved by
using the present base-catalyzed strategy, producing the
corresponding 1,2-bisphosphoryl compounds in good yields
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applicable to the diphosphorylation of acetylene (eq 2). Thus, in
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7307-7315; (c) Angell, Y. L.; White, K. M.; Angell, S. E.; Mack,
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2
6
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3
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diylbis(diphenylphosphine oxide) 1t was isolated in 78% yield.
13
By using a known procedure, compound 1t could be easily
reduced to be the useful bidentate phosphine ligand 1,2-
bis(diphenylphosphanyl)ethane (dppe).
7
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1
In conclusion, we have developed an efficient transition-
metal-free double addition of H-phosphine oxides to alkynes. In
the presence of a catalytic amount of t-BuOLi, various 1,2-
bisphosphoryl compounds including those with functional groups
were produced in high yields. This reaction was simple and easy-
to-handle, which provides a convenient clean protocol for the
preparation of the useful 1,2-bisphosphoryl compounds.
8
9
5
1
Supplementary data
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Supplementary data was associated with this article.
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2
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


An efficient base-catalyzed (transition metal-free) double addition of H-phosphine oxides to alkynes
is developed.
In the presence of a catalytic amount of t-BuOLi, various 1,2-bisphosphoryl compounds were
produced in high yields.
This method provides an easy direct way to prepare bisphosphine oxides that are of high importnace
in organic synthesis.