Hydrophosphonylation of Alkynes with Trialkyl Phosphites Catalyzed by Nickel

Article abstract of DOI:10.1002/cctc.201700974

The use of simple and inexpensive NiCl₂?6 H₂O as a catalyst precursor for C?P bond formation in the presence of commercially available trialkyl phosphites (P(OR)₃, R=Et, iPr, Bu, SiMe₃) along with several alkynes is presented. Control experiments showed the in situ formation of (RO)₂P(O)H as the species that undergo the addition into the C≡C bond at the alkynes to yield the product of P?H addition. The hydrophosphonylation of diphenylacetylene with P(OEt)₃, P(OiPr)₃, and P(OSiMe₃)₃ proceeds in high yields (>92 %) without the need of a specific solvent or ligand. This method is useful for the preparation of organophosphonates for both phenylacetylene as a terminal alkyne model and internal alkynes in yields that range from good to modest.

Full text of DOI:10.1002/cctc.201700974

DOI: 10.1002/cctc.201700974
Full Papers
Hydrophosphonylation of Alkynes with Trialkyl Phosphites
Catalyzed by Nickel
Rosa E. Islas and Juventino J. Garcꢀa*[a]
The use of simple and inexpensive NiCl2·6H2O as a catalyst pre-
cursor for CÀP bond formation in the presence of commercially
available trialkyl phosphites (P(OR)3, R=Et, iPr, Bu, SiMe3) along
with several alkynes is presented. Control experiments showed
the in situ formation of (RO)2P(O)H as the species that undergo
the addition into the CꢀC bond at the alkynes to yield the
product of PÀH addition. The hydrophosphonylation of
diphenylacetylene with P(OEt)3, P(OiPr)3, and P(OSiMe3)3 pro-
ceeds in high yields (>92%) without the need of a specific sol-
vent or ligand. This method is useful for the preparation of or-
ganophosphonates for both phenylacetylene as a terminal
alkyne model and internal alkynes in yields that range from
good to modest.
Introduction
Organophosphonates are an important family of organophos-
phorus compounds with multiple potential applications, which
include halogen-free flame-retardant polymers and antiviral
and anticancer compounds.[1] They can also be used as surface
modifiers of materials, which enables the development of bio-
logical microarrays, drug delivery systems, and immobilized ho-
mogeneous and heterogeneous catalysts.[2]
precursor along with bis(diphenylphosphino)ethane as an an-
cillary ligand in THF for the hydrophosphonylation of several
terminal and internal alkynes.[15] Recently, a modified procedure
was published by the same group, in which no specific sol-
vents or ligands were required to achieve this kind of transfor-
mations; instead they made use of diisobutyl aluminum hy-
dride (DIBAL-H), which is a strong reducing agent that requires
special handling, in conjunction with [Ni(acac)2] to achieve the
full conversion of the starting materials into the desired prod-
ucts.[16] Therefore, the development of new, simple, cheap, and
efficient Ni-based catalytic systems able to perform the addi-
tion of PÀH to unsaturated molecules is needed.
Particularly, vinylphosphonates can be used in the synthesis
of poly(vinylphosphonate)s[3] useful in applications as dental
adhesives,[4] in studies of bone regeneration,[5] and in the de-
velopment of proton-conducting membranes.[6] In addition,
they can be used in a variety of organic reactions[7] and as val-
uable building blocks for the development of biologically
active compounds.[8]
Herein, we present our findings in the study of the hydro-
phosphonylation of several alkynes, by a methodology that
allows the in situ formation of dialkyl phosphites (iPrO)2P(O)H
using commercially available trialkyl phosphites in the pres-
ence of an inexpensive and air-stable catalyst precursor
(NiCl2·6H2O). We optimized the reaction conditions made for
diphenylacetylene (DPA) hydrofunctionalization with triisoprop-
yl phosphite (P(OiPr)3) to obtain the corresponding vinyl-
phosphonate. Control experiments showed that P(OiPr)3 is
transformed into (iPrO)2P(O)H under the optimized reaction
conditions, and we propose that this species is responsible for
the alkyne hydrofunctionalization reaction. Then, P(OR)3 (R=Et,
Bu, SiMe3) were tested under the optimized conditions, and
we obtained high conversion rates and yields for the reaction
with DPA, followed by the use of internal alkynes and phenyla-
cetylene as a terminal alkyne model under the same reaction
conditions to produce the corresponding vinyl- and alkyl-
phosphonates with yields that ranged from good to modest.
Finally, a plausible catalytic cycle was proposed based on our
experimental findings and the results of other studies that are
closely related.
A variety of methods to obtain vinylphosphonates has al-
ready been reported.[9] Among these methods, the addition of
PÀH to unsaturated molecules catalyzed by costly elements,
such as Pd and Rh, is an important methodology to obtain this
type of compound.[10] In recent years there has been a growing
interest in the development of less expensive Ni-based cata-
lysts for CÀC[11] and CÀP[12] bond formation.[13]
In this regard, low-valence Ni complexes [Ni(PPh2Me)4] or
Ni(cod)2/PPhMe2 (cod=cyclooctadiene) have been reported as
catalyst precursors in the addition of H-phosphonates to termi-
nal alkynes under very mild reaction conditions to produce the
corresponding vinylphosphonates.[14] In 2010, Beletskaya and
co-workers showed that air-stable [Ni(acac)2] (acac=acetylacet-
onate) can be used instead of Ni0 complexes as catalyst
[a] R. E. Islas, Prof. J. J. Garcꢀa
Facultad de Quꢀmica
Universidad Nacional Autꢁnoma de Mꢂxico
Mꢂxico D. F. 04510 (Mꢂxico)
E-mail: juvent@unam.mx
Supporting information and the ORCID identification number(s) for the
author(s) of this article can be found under https://doi.org/10.1002/
cctc.201700974.
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The effect of the variation of the concentration of the phos-
phites in the model reaction was examined (Table 3). The
impact of the initial concentration of P(OiPr)3 also influences in
the performance of the reaction, that is, the use of 2 equiva-
lents (entry 2) or more (entry 1) of the initial phosphite allowed
the formation of the corresponding vinylphosphonate. Howev-
er, the use of less than 2 equivalents of the phosphite
decreased the conversion to 91%.
Results and Discussion
Initially, we assessed the reactivity of P(OiPr)3 in the hydrophos-
phonylation reaction of DPA (1) with different amounts of
NiCl2·6H2O at different reaction times (Table 1). Remarkably, no
solvent, ligand, or any other additive was required to reach the
Table 1. Optimization of reaction conditions for hydrophosphonylation.[a]
The effect of solvent was also investigated, and the
results are summarized in Table 4. The use of both
coordinating and non-coordinating solvents afforded
the desired products. The use of non-coordinating
solvents (toluene and mesitylene) led to a higher
conversion of DPA (entries 1 and 2) in comparison
with the use of coordinating solvents (THF and diox-
ane; entries 3 and 4). However, the catalytic reaction
also showed a good performance under neat condi-
Entry
NiCl2·6H2O
[mol%]
t
[h]
Conversion of 1
[%]
Selectivity [%]
tions. Consequently, these conditions were chosen to
perform some control experiments, that is, without
the use of the Ni catalyst precursor. These experi-
ments showed a poor conversion of the initial alkyne
(entry 6).
2
3
4
1
2
3
4
5
6
7
20
10
5
3
3
24
24
24
24
48
48
42
100
100
100
60
100
100
100
90
99
98
92
93
92
96
3
7
<1
1
<1
1
3
2
3
1
5
4
Additionally, to elucidate if the water molecules of
the Ni precursor were responsible for the hydrolysis
of the triisopropyl phosphite, the reaction was per-
formed using 0.1 mmol of distilled water and, once
again, without using the Ni catalyst (entry 7). Under
these conditions, the reaction was also inhibited
(entry 7); as a consequence of the hydrolysis of
P(OiPr)3, (iPrO)2P(O)H was also detected.[18] A homo-
geneity test was performed by adding a mercury
1
1
5
3
[a] All reactions were performed in a Schlenk flask (50 mL) equipped with a Rotaflo
valve and heated at 1608C. Reaction conditions: molar ratio of 1:2:x of DPA, triiso-
propyl phosphite, and NiCl2·6H2O, respectively. Conversions and selectivity were de-
termined by using GC–MS.
complete conversion of DPA to diisopropyl [(E)-1,2-diphenylvi-
nyl]phosphonate (2; >90%). The use of 1% of NiCl2·6H2O for
42 h produced the corresponding product 2 in a high yield
(96%; entry 7). Notably, compound 2 was isolated as the only
isomer as observed in the chromatograms of the crude reac-
tion mixture (Schemes S1–S6). Moreover, this compound was
isolated with a yield of 91% and its stereochemistry was as-
Table 2. Performance of different Ni precursors in the hydrophosphonyla-
tion reaction (Scheme 1).[a]
Entry
Catalyst precursor
Conversion of 1 [%]
Selectivity to 2 [%]
1
1
2
3
4
NiBr2·3H2O
NiCl2·6H2O
NiF2
100
100
1
nd
96
100
92
signed by using H NMR spectroscopy, which showed a cou-
pling constant of JP,H cis =22.3 Hz in concordance with previous
reports.[15] Thus, we decided to use these conditions for further
experiments. In all cases, we detected the formation of small
amounts of hexaphenylbenzene (3), a product of the cyclotri-
merization reaction of the alkyne,[17] and cis-stilbene (4) from
the semihydrogenation of the alkyne.
[Ni(cod)2]
92
[a] All reactions were performed in a Schlenk flask (50 mL) equipped with
a Rotaflo valve and heated at 1608C for 42 h. Reaction conditions: molar
ratio of 1:2:0.01 of DPA, triisopropyl phosphite, and the nickel compound,
respectively. Conversions and selectivity were determined by using GC–
MS. nd=not detected.
The performance of a variety of similar Ni catalyst precursors
was evaluated in the model hydrophosphonylation reaction
(Table 2). The use of NiCl2·6H2O showed the best results (yield
96%); however, the use of NiBr2·3H2O (entry 1) does not pro-
duce any addition product, instead, we observed an uncharac-
terized colorless polymeric byproduct. The use of NiF2 (entry 3)
allowed a poor conversion of DPA, probably because of solu-
bility issues. If [Ni(cod)2] was used, we observed a 92% conver-
sion of the alkyne to produce 2 in high yields. Notably, it has
been reported that the use of [Ni(cod)2] only affords traces of
product at 1208C after 19 h with (iPrO)2P(O)H as the P
source.[16] Thus, NiCl2·6H2O was selected as standard catalyst
precursor for the subsequent reactions.
Table 3. Effect of P(OiPr)3 concentration in the model hydrophosphonyla-
tion of DPA (Scheme 1).[a]
Entry P(OiPr)3 [mmol/equiv.] Conversion of 1 [%] Selectivity to 2 [%]
1
2
3
5.04/3
3.36/2
2.52/1
100
100
91
97
96
89
[a] All reactions were performed in a Schlenk flask (50 mL) equipped with
a Rotaflo valve and heated at 1608C for 42 h. Reaction conditions: molar
ratio of 1:x:0.01 of DPA, triisopropyl phosphite, and NiCl2·6H2O, respec-
tively. Conversions and selectivity were determined by using GC–MS.
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Table 4. Solvent variations and control experiments (Scheme 1).[a]
Table 5. Formation of (iPrO)2P(O)H (PV species) from trialkyl phosphites
P(OR)3.[a]
Entry
Solvent
Conversion of 1 [%]
Selectivity to 2 [%]
1
2
3
4
Toluene
Mesitylene
Dioxane
THF
100
100
32
97
98
100
98
28
5
Neat
Neat
Neat
Neat
100
24
16
96
73
90
97
6[b]
7[c]
8[d]
Entry
R
Conversion of 5
Selectivity [%]
[%]
6
7
8
99
1
2
3
4
5[b]
iPr
Et
Bu
Si(Me)3
iPr
42
29
12
45
4
90
55
58
91
12
1
21
17
nd
13
9
[a] All reactions were performed in a Schlenk flask (50 mL) equipped with
a Rotaflo valve and 1.5 mL of solvent at 1608C for 42 h. Reaction condi-
tions: molar ratio of 1:2:0.01 of DPA, triisopropyl phosphite, and
NiCl2·6H2O, respectively. [b] Control experiment: molar ratio of 1:2 of
DPA, and triisopropyl phosphite. [c] Molar ratio of 1:2:0.1 of DPA, triiso-
propyl phosphite, and distilled water, respectively. [d] Molar ratio of
1:2:0.01:0.05 of DPA, triisopropyl phosphite, NiCl2·6H2O, and metallic Hg,
respectively. Conversions and selectivity were determined by using GC–
MS.
24
25
9
75
[a] All reactions were performed in a Schlenk flask (50 mL) equipped with
a Rotaflo valve. Reaction conditions: molar ratio of 2:0.01 of trialkyl phos-
phite and NiCl2·6H2O, respectively. [b] Control experiment under Ni-free
conditions. nd=not detected. Conversions and selectivity were deter-
mined by using GC–MS.
drop into the NiCl2·6H2O reaction system (entry 8), and no de-
crease in the DPA conversion or yield was observed. Therefore,
we conclude that the reaction was homogeneous.
The PIII atom in the starting phosphite was oxidized to the
corresponding PV phosphonate (Scheme 1). A similar transfor-
mation was reported by Lu and Zhu who used NiCl2 to pro-
mote the oxidation of PIII to PV (Scheme 2).[19]
used as starting materials for the synthesis of (RO)2P(O)H (en-
tries 2–4). Notably, P(OiPr)3 and P(OSiMe3) gave a better yield
of (RO)2P(O)H than the other two PIII sources (entries 1 and 4).
We extended the scope of the hydrophosphonylation reac-
tion using P(OEt)3, P(OBu)3, and P(OSiMe3), and the results
were compared with those obtained with P(OiPr)3 (Table 6). If
P(OSiMe3) was used as the PIII source, it was possible to detect
the hydrophosphonylation product in high conversion and
yields (Table 6, entry 4), which can be related to the higher
concentration of the PV species (Me3SiO)2P(O)H (Table 5,
entry 4). The use of P(OEt)3 and P(OBu)3 led to low yields of
the hydrophosphonylation product (Table 6, entries 1 and 3) in
concordance with the low yields of the PV species (OR)2P(O)H
(Table 5, entries 2 and 3). However, the low yields obtained
with the use of P(OEt)3 and P(OBu)3 can be overcome by using
a higher catalyst loading (10%; Table 6, entries 5 and 6).
Several aromatic alkynes were used under the catalytic reac-
tion conditions, and the results are summarized in Table 7. In
general, high conversions of functionalized DPAs (1a, 1c–1e)
were observed, with the exception of 1-methyl-4-(2-phenyle-
thynyl)benzene (Me-DPA; 1b), which produced 76% conver-
sion. 1-(4-phenylethynyl-phenyl)-ethanone (MeOC-DPA; 1a;
entry 1) and the symmetric alkyne 1e (entry 5) both gave the
corresponding vinylphosphonates in high yields. If 1-methoxy-
4-(2-phenylethynyl)benzene (MeO-DPA; 1c) was used, the side
reaction product that corresponds to the semihydrogenation
of the alkynes was preferred to produce the corresponding stil-
benes (17d) in high yields (82%; entry 4) with a low preference
to the hydrophosphonylation products (11%; entry 4).
If we consider the above, we propose that under the opti-
mized conditions NiCl2·6H2O promotes the in situ formation of
(iPrO)2P(O)H (a PV species) from P(OiPr)3, which is involved in
the formation of the alkyne hydrophosphonylation product. To
corroborate this, we performed a series of hydrophosphonyla-
tion experiments to confirm the formation of PV (Table 5).
(OiPr)2P(O)H was obtained as the major product from P(OiPr)3
in the presence of the Ni catalyst (entry 1). The formation of
the phosphonates (O)P(iPr)(OiPr)2 and the phosphates
(O)P(OiPr)3 was also detected under the optimized hydrophos-
phonylation conditions. If a control experiment was performed
without NiCl2·6H2O, only a trace amount of (OiPr)2P(O)H was
observed (entry 5). P(OEt)3, P(OBu)3, and P(OSiMe3) were also
Scheme 1. Hydrophosphonylation of DPA using NiCl2·6H2O.
To extend the scope of this reaction, a series of
nonaromatic alkynes was assessed (Table 8). Notably,
a higher load of catalytic precursor was required to
perform the alkyne hydrophosphonylation with
P(OEt)3 in comparison to P(OiPr)3. Again, this can be
related to the lower concentration of (EtO)2P(O)H
formed with P(OEt)3 (vide supra). The hydrophospho-
Scheme 2. Reported formation of PV by trialkyl phosphites using NiCl2.[19]
nylation of disubstituted alkynes required more
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the use of low loadings of the Ni precatalyst (1% mol) (entry 3)
favored the cyclotrimerization (89% yield) over the alkyne hy-
drophosphonylation. This kind of cyclotrimerization product is
formed frequently in the presence of NiII precursors.[22]
If we performed the reaction with P(OEt)3 and 1-phenyl-1-
propyne, the corresponding monophosphonate 9i was ob-
tained in good yield (entry 4) along with the formation of the
mono- and divinylphosphonates 13i and 14i in poor yields. If
P(OiPr)3 was used, compound 9j was the only phosphonate
produced, along with the corresponding cyclotrimer 16j
(entry 5). Notably, the cyclotrimerization products can be re-
duced or halted by adding an excess of the PIII source (en-
tries 6 and 7).
Table 6. Scope of trialkyl phosphites in hydrophosphonylation of DPA.[a]
Entry
NiCl2·6H2O
[equiv.]
P(OR)3
Conversion of 1
[%]
Selectivity to 2
[%]
1
2
3
4
5[b]
6[b]
P(OEt)3
32
100
18
100
100
56
10
96
22
98
92
P(OiPr)3
P(OBu)3
P(OSiMe3)3
P(OEt)3
0.01
0.1
The selectivity was affected by using 4-phenyl-3-butyn-2-one
(entries 8–9) in which the formation of alkylphosphonates is
preferred over that of the vinylphosphonates. The introduction
of an electron-withdrawing substituent conjugated to the
triple bond modified the electron density around this triple
bond to undergo a Ni-catalyzed hydrogenation. The hydroge-
nation of a,b-unsaturated carbonyl compounds has already
been performed with the use of NiI and NiII catalytic precur-
sors.[23] The formation of alkylphosphonates 11 n and 15n was
preferred in the presence of P(OiPr)3 over the corresponding vi-
nylphosphonates 9n and 13n. We also found the opposite if
we used P(OSiMe3): vinylbisphosphonate 10o species were
preferred over the less sterically hindered monophosphonated
species (entry 10).
P(OBu)3
100
[a] All reactions were performed in a Schlenk flask (50 mL) equipped with
a Rotaflo valve and 1.5 mL of solvent. Reaction conditions: molar ratio of
1:2:0.01 of DPA, trialkyl phosphite, and NiCl2·6H2O, respectively. [b] Molar
ratio of 1:2:0.1 of DPA, trialkyl phosphite, and NiCl2·6H2O, respectively.
Conversions and selectivity were determined by using GC–MS.
forceful reaction conditions than those used for terminal al-
kynes.[20] Steric effects have an important effect on the selectiv-
ity, as evidenced by the higher number of byproducts ob-
served by using P(OEt)3 than P(OiPr)3.[21]
However, if we used phenylacetylene as the substrate, the
formation of bisphosphonated species 10 f is favored if P(OEt)3
is used as a PIII source (Table 8, entry 1), whereas the mono-
phosphonated species 9g is preferred if the more sterically
hindered P(OiPr)3 is used as the PIII source (Table 8, entry 2). In
both cases, 1,3,5-triphenylbenzene was also obtained as a
result of the cyclotrimerization of phenylacetylene. Moreover,
Proposed mechanism
If we consider both the findings of the current work and the
results of studies that are related closely,[16,24] a mechanism is
proposed for the hydrophosphonylation of alkynes (Scheme 3).
The first step involves the formation of a Ni0 complex
from NiCl2·6H2O and P(OR)3. It is known that NiII hal-
ides are reduced to Ni0 by trialkyl phosphites, which
are strong reducing agents, to obtain trialkyl phos-
phates as the main oxidation product.[24a–c] The for-
mation of the trialkyl phosphates was detected ex-
perimentally under the optimized hydrophosphonyla-
tion conditions (Figure S1) also in the experiments in
which the formation of PV species takes place from
PIII sources (Table 5, entries 1–4, Figures S9–S12).
Once the Ni0 species is formed, the next step is the
oxidative addition of (RO)2P(O)H, to produce A. This
Table 7. Results for substituted aromatic alkynes used under catalytic conditions.[a]
is followed by the coordination of the alkyne to the
metal–hydride complex to yield B, which evolves into
the alkenyl complex C by an insertion of the alkyne
into the NiÀH bond.[24d] The vinylphosphonate was
obtained by the reductive elimination of the product
and catalyst regeneration.
Entry
1
R1
R2
Conversion of 1
[%]
Selectivity [%]
2
17
1
2
3
4
5
1a
1b
1c
1d
1e
COMe
Me
Cl
OMe
OMe
H
H
H
H
100
76
97
80
96
98[c]
nd
nd
>99
82[b]
100[c]
nd
11[c]
98
OMe
nd
[a] All reactions were performed in a Schlenk flask (50 mL) equipped with a Rotaflo
valve and 1.5 mL of toluene. Reaction conditions: molar ratio of 1:2:0.01 of functional-
ized DPA, triisopropyl phosphite, and NiCl2·6H2O, respectively. [b] (E/Z)-Stilbenes were
detected. [c] Regioisomeric mixture of the corresponding hydrophosphonylation prod-
ucts were detected. nd=not detected. Conversions and selectivity were determined
by using GC–MS.
Conclusions
We have demonstrated that inexpensive and easy to
handle NiCl2·6H2O is an effective catalyst precursor
for PÀC bond formation reactions using alkynes and
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Table 8. Results for terminal and substituted alkynes used under catalytic conditions.[a]
Entry
Alkyne, phosphite
t
T
Selectivity [%]
[h]
[8C]
9
10
11
12
13
14
15
16
1[b,d,e]
2[b,d]
3[a,d]
4[b,d]
5[a,d]
6[c,d]
7[c,d]
8[b]
1 f=R3 =H, R=Et
24
24
24
24
42
42
42
24
42
42
130
130
130
160
160
160
160
160
160
160
4
46
7
66
43
92
99
nd
nd
3
38
9
4
nd
nd
nd
nd
nd
nd
94
nd
nd
nd
nd
nd
nd
nd
12
37
3
nd
10
nd
nd
nd
nd
nd
84
nd
nd
9
nd
nd
7
nd
nd
nd
nd
nd
nd
7
nd
nd
nd
nd
nd
nd
nd
nd
55
nd
24
35
89
10
57
8
nd
4
nd
nd
1g=R3 =H, R=iPr
nd
nd
17
nd
nd
nd
nd
1h=R3 =H, R=iPr
1i=R3 =Me, R=Et
1j=R3 =Me, R=iPr
1k=R3 =Me, R=iPr
1l=R3 =Me, R=SiMe3
1m=R3 =COMe, R=Et
1n=R3 =COMe, R=iPr
1o=R3 =COMe, R=SiMe3
9[a]
nd
nd
10[a]
[a] All reactions were performed in a Schlenk flask (50 mL) equipped with a Rotaflo valve. Reaction conditions: molar ratio of 1:2:0.01 of alkyne, trialkyl
phosphite, and NiCl2·6H2O, respectively. [b] Molar ratio of 1:2:0.1 of alkyne, trialkyl phosphite, and NiCl2·6H2O, respectively. [c] Molar ratio of 1:4:0.01 of
alkyne, trialkyl phosphite, and NiCl2·6H2O, respectively. [d] Regioisomeric mixtures of the corresponding hydrophosphonylation products were detected.
[e] Additionally, 18% E/Z isomers of [4-phenylbut-1-en-3-ynyl]benzene was observed. nd=not detected. Conversions and selectivity were determined by
using GC–MS.
readily available trialkyl phosphites, which make this method
suitable for practical application in the preparation of organo-
phosphorated compounds of relevance in organic synthesis.
Remarkably, this reaction did not require any additives to
reach the complete conversion of the reactants into the de-
sired organophosphorus products. Experimental evidence led
us to propose that (iPrO)2P(O)H is an active species.
It was also demonstrated that this method is applicable to a
variety of alkynes. Symmetrical aromatic alkynes (diphenylace-
tylene and 1,2-bis(4-methoxyphenyl)ethyne) produced the cor-
responding vinylphosphonates in high yields in the presence
of P(OR)3 (R=Et, SiMe3, or iPr). Phenylacetylene produced
mono- or diphosphonated species under milder reaction con-
ditions than those used with other disubstituted alkynes, and
the regioselectivity was determined by the steric hindrance of
the trialkyl phosphite used. With the use of substrates such as
1-phenylpropyne in the presence of P(OEt)3, several products
were observed because of a low reaction selectivity; this can
be improved by using more sterically hindered phosphites
(P(OiPr)3 or P(OSiMe3)3) to yield the monophosphonated
species.
Scheme 3. Proposed mechanism for the hydrophosphonylation of alkynes.
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this time, the reaction mixture was cooled to RT, exposed to air, fil-
tered through Celite, and then analyzed by using GC–MS.
The use of 4-phenyl-3-butyn-2-one allowed the production
of alkylphosphonates instead of vinylphosphonates in the
presence of P(OiPr)3 and P(OEt)3, whereas the use of P(OSiMe3)
produced the corresponding diphosphonate as the main prod-
uct. The regioselectivity with unsymmetrical alkynes needs fur-
ther investigation.
Detection of (OR)2P(O)H from P(OR)3 using NiCl2·6H2O
Typically, a Schlenk flask (50 mL) fitted with a Rotaflo valve was
charged with NiCl2·6H2O (4 mg, 0.0168 mmol) and a given trialkyl
phosphite (3.36 mmol). The flask was heated at 1608C for 42 h.
After this time, the reaction mixture was cooled to RT, exposed to
air, filtered through Celite, and analyzed by using GC–MS. White
precipitates were observed.
Experimental Section
All experiments were performed in oven-dried Schlenk tubes in a
glovebox (MBraun Unilab) under high-purity Ar (Praxair 99.998%)
and controlled concentrations of water and oxygen (<1 ppm). All
liquid reagents were purchased from Aldrich and Merck and they
were degassed and stored in a glovebox for further use. All sol-
vents were dried using standard techniques and stored in the glo-
vebox before use. Alkynes 1a–1d were prepared following a
method reported previously.[25] Alkynes (diphenylacetylene, phenyl-
acetylene, 1-phenyl-1-propyne, and 4-phenyl-3-butyn-2-one) and
phosphites P(OEt)3, P(OiPr)3, P(OBu)3, and P(OSiMe3)3 were pur-
chased from Aldrich and stored in the glovebox before use.
Column chromatography was performed using Silica Gel 60 (parti-
cle size 63–200 mm). Deuterated solvents were purchased from
Cambridge Isotope Laboratories. NMR spectra of organic products
were acquired at RT by using a 300 MHz Varian Unity spectrometer.
Chemical shifts in the 1H NMR spectra (d, ppm) are reported ac-
cording to the residual solvent peaks. 31P{1H} NMR spectra are refer-
enced to the d=0 ppm signal of external 85% H3PO4. GC–MS was
performed by using an Agilent Technologies G3171A equipped
Reaction scope with trialkyl phosphites
Typically, a 50 mL Schlenk flask fitted with a Rotaflo valve was
charged with NiCl2·6H2O (4 mg, 0.0168 mmol), DPA (300 mg,
1.68 mmol), and a given trialkyl phosphite (3.36 mmol). The flask
was heated at 1608C for 42 h. After this time, the reaction mixture
was cooled to RT, exposed to air, filtered through Celite, and ana-
lyzed by using GC–MS. Orange-colored solutions were observed.
Reaction scope with alkynes
Typically, a 50 mL Schlenk flask fitted with a Rotaflo valve was
charged with NiCl2·6H2O (4 mg, 0.0168 mmol), P(OR)3 (3.36 mmol),
a given alkyne (1.68 mmol), and toluene (1.5 mL; the experiments
indicated in Table 8 were performed under neat conditions). The
flask was heated at 1608C for 42 h. After this time, the reaction
mixture was cooled to RT, exposed to air, filtered through Celite,
and analyzed by using GC–MS.
with
a
5% phenylmethylsilicone (30 mꢂ0.25 mmꢂ0.25 mm)
column.
Diisopropyl[(E)-1,2-diphenylvinyl]phosphonate]:
1H NMR
(300 MHz, CDCl3): d=1.18 (d, JH,H =6.0 Hz, 6H), 1.25 (d, JH,H =6.0 Hz,
6H), 4.60 (m, 2H), 6.99–7.02 (m, 2H), 7.08–7.11(m, 3H), 7.24–7.26
(m, 5H), 7.57 ppm (d, JH,H =24.0 Hz, 1H); 13C NMR (75 MHz, CDCl3):
d=23.89, 23.96, 24.13, 24.18, 71.01,127.62, 128.22, 128.69, 128.82,
129.53, 129.6, 130.39, 132.74 (JP,C =179.25 Hz), 134.93, 135.23,
135.91,136.01,142.78 ppm (JP,C =10.5 Hz); 31P NMR (121.44 MHz,
CDCl3): d=15.83 ppm.
Catalytic hydrophosphonylation of DPA
Typically, NiCl2·6H2O (4 mg, 0.0168 mmol), DPA (300 mg,
1.68 mmol), and P(OiPr)3 (701 mg, 3.36 mmol) were placed in a
Schlenk flask (50 mL) fitted with Rotaflo valve. The color of the so-
lution turned immediately to dark blue. Then, the flask was taken
out from the glovebox and heated at 1608C for 42 h (except in the
experiments indicated in Table 1). After this time, the reaction mix-
ture was cooled to RT, exposed to air, filtered through Celite, and
then analyzed by using GC–MS. Usually, orange-colored solutions
were observed.
Acknowledgements
We thank CONACYT 178265 and PAPIIT-DGAPA-UNAM 202516 for
their financial support of this work. R.E.I. thanks CONACYT
(245557) for a graduate studies grant. We also thank Dr. Alma
Arꢂvalo for her technical assistance.
After the completion of the reaction, product 2 was purified by
column chromatography with silica gel (particle size 63–200 mm,
hexane/ethyl acetate as eluent), and the product was isolated in
91% yield as a yellow oil.
Mercury drop test
Keywords: alkynes
·
homogeneous catalysis
· nickel ·
phosphorus · reaction mechanisms
Following the procedure described above, the same reaction was
performed with the addition of one drop of elemental Hg to the
reaction mixture. At the end of each run, the reaction mixture was
cooled to RT, exposed to air, filtered through Celite, and analyzed
by using GC–MS. Usually, orange-colored solutions were observed.
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Manuscript received: June 14, 2017
Revised manuscript received: July 7, 2017
Accepted manuscript online: July 21, 2017
Version of record online: && &&, 0000
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R. E. Islas, J. J. Garcꢀa*
&& – &&
Hydrophosphonylation of Alkynes
with Trialkyl Phosphites Catalyzed by
Nickel
Back to the hydrophosphonylation:
The use of inexpensive NiCl2·6H2O as a
catalyst precursor for CÀP bond forma-
tion in the presence of commercially
available trialkyl phosphites (P(OR)3,
R=Et, iPr, Bu, SiMe3) along with several
alkynes is presented. (RO)2P(O)H formed
in situ undergoes addition to the alkyne
CꢀC bond. The hydrophosphonylation
of diphenylacetylene with P(OEt)3,
P(OiPr)3, and P(OSiMe3)3 proceeds in
high yields (>92%) without the need of
a specific solvent or ligand.
&
ChemCatChem 2017, 9, 1 – 8
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ꢁ 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÝÝ These are not the final page numbers!