1,1-Diphosphines and divinylphosphines via base catalyzed hydrophosphination

Article abstract of DOI:10.1039/C8CC05890C

A catalytic hydrophosphination route to 1,1-diphosphines is yet to be reported: these narrow bite angle pro-ligands have been used to great effect as ligands in homogeneous catalysis. We herein demonstrate that terminal alkynes readily undergo double hydrophosphination with HPPh₂ and catalytic potassium hexamethyldisilazane (KHMDS) to generate 1,1-diphosphines. A change to H₂PPh leads to the formation of P,P-divinyl phosphines.

Full text of DOI:10.1039/C8CC05890C

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Authors
N. T. Coles,a M. F. Mahona and R. L. Webstera
Affiliations
a Department of Chemistry, University of Bath, Bath, UK. BA2 7AY.
Acknowledgements
The University of Bath is thanked for a studentship (NTC). The EPSRC UK National Mass
Spectrometry Facility at Swansea University is thanked for mass spectrometry analyses.
Crystallization of 1b was undertaken by Kimberley J. Gallagher.

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1,1-Diphosphines and divinylphosphines via base catalyzed
hydrophosphination
Received 00th January 20xx,
Accepted 00th January 20xx
Authors
DOI: 10.1039/x0xx00000x
www.rsc.org/
A catalytic hydrophosphination route to 1,1-diphosphines is yet to performed
a
comprehensive
study
regarding
be reported: these narrow bite angle pro-ligands have been used hydrophosphination of non-terminal alkynes using 22 mol%
to great effect as ligands in homogeneous catalysis. We herein KOtBu as the catalyst, but with the addition of NEt3 as a
demonstrate that terminal alkynes readily undergo double solvent.31 The limitations of this reaction lie not only in the fact
hydrophosphination with HPPh2 and catalytic potassium that only three or four catalytic turnovers per potassium
hexamethyldisilazane (KHMDS) to generate 1,1-diphosphines. A centre were achieved, but also in the lack of selectivity
change to H2PPh leads to the formation of P,P-divinyl phosphines.
obtained: the phosphinoalkene product was obtained as a
mixture of E and Z isomers and often the reaction was
contaminated with tetraphenyldiphosphine, (Ph2P)2.
Bidentate phosphines constitute an immensely important class
of compounds used throughout synthetic chemistry, where
they are commonly employed as ligands in transition metal
catalysis.1-3 An array of diphosphines have been prepared and
the effect of the phosphine bite angle has been studied in
catalysis.4 Narrow bite-angle 1,1-diphosphines, whereby the
phosphorus is linked by a single methylene (or methine) group,
have been used with great success in catalytic
We herein report a mild, facile and selective route to a
homologous series of 1,1-diphosphines using alkynes and a
catalytic amount of KHMDS (Scheme 1c). The most similar
reported methodology and range of products of which we are
aware has come from Leung. Using ethyl propiolate and but-3-
yn-2-one, a chiral template approach was employed by Leung
giving a 1:2 mixture of the stereoisomeric 1,1-diphosphine
ligated Pd complexes.32 Interestingly, the 1,1-diphosphine Pd-
complex was formed using catalytic amounts of NEt3 but the
1,2-diphosphine Pd-complex was formed in the presence of
excess NEt3. HCl (conc.) followed by KCN (aq.) washes were
necessary to release the phosphine from the Pd template.
hydrofunctionalization,5-13
hydrogenation14-16
and
epoxidation,17-19 to name but three reaction classes. However,
unlike many ligand series used in catalysis, reports of a truly
diverse homologous series of 1,1-diphosphine compounds are
scarce.20 Commercially available examples of the free ligand
are limited to bis(dimethylphosphino)methane (DMPM),
bis(dicyclohexylphosphino)methane and bis(diphenylphos
phino)methane (DPM). The range of functionality that can be
tolerated is linked to the challenges associated with the
synthesis of such pro-ligands: commonly reaction of the
deprotonated phosphine with a dihalomethane is necessary
(Scheme 1a).21-24 The α-deprotonation of a methyl-diaryl/alkyl
phosphine and subsequent reaction with a chlorophosphine, is
also known (Scheme 1b).25-27 Both methods are synthetically
wasteful, but the latter can give access to unsymmetrically
substituted 1,1-diphosphines.
The stoichiometric reaction of a base with phosphines and
alkynes has been known for many years.28, 29 One of the first
examples where a base was used catalytically (25 mol%
loading of PhLi) was demonstrated by Märkl and Potthast to
prepare phospholes.30 Bookham and Smithies subsequently
Scheme 1. 1,1-diphosphines can be formed from stoichiometric reaction of a
halide, phosphine and base whereas this work shows that they can also form
using catalytic hydrophosphination chemistry.
Electronic Supplementary Information (ESI) available: [Synthetic methods, starting
See
material
and
product
DOI: 10.1039/x0xx00000x
analysis
data
and
NMR
spectra].
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Following short optimization procedure using ethyl
Journal Name
KHMDS (10 mol%)
HPPh2 (1 mmol)
a
R
Ph2P
R
propiolate as our standard substrate, we found that activated
alkynes can readily undergo base catalyzed double
hydrofunctionalization to yield 1,1-diphosphines at room
temperature without the need for any reagents in excess.
Weak bases such as K2CO3 or NEt3 do not achieve good
selectivity or yield. As an inexpensive and easy to handle base,
10 mol% NaOtBu gives quantitative spectroscopic yield of 1b in
6 h. Comparable spectroscopic yields of 1b are also achieved in
6 h using KOtBu, NaHMDS and KHMDS. When the loading of
these bases is lowered to 1 mol% it is still possible to achieve
very high conversion (>90%, see supporting information for
base optimisation). After 16 h at RT in the absence of any base
7% 1b is obtained along with 49% vinyl phosphine (3 : 1
mixture of E and Z isomers) and unreacted HPPh2. When we
proceeded to investigate reactivity with other alkynes, we
found that NaOtBu is not a suitable catalyst. For example, 3-
ethynylpyridine only generates 1o in 17% spectroscopic yield
with NaOtBu, a change of alkali metal to KOtBu increases the
yield to 38%, but it is only when a change to KHMDS is
exercised that a high spectroscopic yield of 1i is obtained
(92%). This is presumably linked to the non-nucleophilic
character of KHMDS which leads to cleaner reactivity (multiple
side-products are formed from the reaction of NaOtBu and
KOtBu). This trend is observed across other classes of
substrate: see supporting information for reaction monitoring
using NaOtBu, KOtBu and KHMDS with each class of substrate.
Hydrophosphination does not proceed in CH2Cl2, C6H6 or C6H5F
and thus we investigated substrate scope using 10 mol%
KHMDS in MeCN (Scheme 2).
PPh2
Isolated yield, %
MeCN
RT, 6 h
0.5 mmol
Esters
Ph2P
OMe Ph2P
OEt Ph2P
OtBu
Ph2P
OPh
PPh2
O
PPh2
O
PPh2
O
PPh2 O
1a, 86
1b, 79
1c, 75
1d, 5933
Amides
Ph2P
NMe2 Ph2P
NMePh
Ph2P
NHPh Ph2P
NH2
PPh2
O
PPh2
O
PPh2
O
PPh2 O
1e, 88
1f, 86
1g, 62
1h, 94
Ketones
Ph Ph2P
Ph2P
PPh2
O
PPh2 O
1j, 1133
1i, 6433
Imines
Ph2P
Ph2P
NHPh
NPh Ph2P
+
NHPh
PPh2 iPr
PPh2 Ph
1k, 41
PPh2 iPr
1l, major
1l', minor
80 (76:24)
Ph2P
iPrHN
Ph2P
Ph
Ph2P
NiPr
NHiPr
+
+
PPh2 Ph
PPh2 Ph
1m', minor
1m, major
1m'', minor
PPh2
57 (75:18:7)
Pyridines
Ph2P
N
Ph2P
Ph2P
N
PPh2
PPh2
PPh2
N
1n, 92
1o, 85
1p, 74
In general, the reaction appears to benefit from carbonyl
functionality α to the alkyne and thus other propiolates give
high yield of the desired product (1a to 1d33). Both tertiary (1e
and 1f), secondary (1g) and primary (1h) propargyl amides and
aromatic ketones (1i33) have been functionalized with good
isolated yield. Aliphatic ketones give low yield of product (1j33).
Imines also react well but undergo concomitant
Scheme 2. 1,1-Diphosphines formed from the reaction of functionalized
acetylenes with HPPh2 in the presence of 10 mol% KHMDS.
tautomerization to give the enamine (1k to 1m/1m’/1m’’). We
are pleased to report that ethynylpyridines can be used in the
transformation and that the substitution pattern has little
bearing on the level of reactivity observed (1n to 1p).
Unfortunately, the reaction is not as clean when other aryl
acetylenes are employed.34
Crystals of 1b
,
1f
,
1i and 1k were isolated (see Figure 1 for 1b
1i and 1k). The compounds
and supporting information for 1f
,
Figure 1. Molecular structure of 1b. Ellipsoids are represented at 30%. With the
exception of methine protons, all hydrogen atoms have been omitted for clarity.
all have fairly disparate P-C-P bond angles. This is, presumably,
linked to sterics of the pendant functional group with the
tertiary amide of 1f providing the greatest steric bulk and A radical clock study of our standard reaction (0.5 mmol ethyl
therefore forcing the P-C-P bond angle to become more acute propiolate, 1 mmol HPPh2, 10 mol% KHMDS, 1 mL MeCN with
(99.41(9) °) than that observed for the ester (1b: 103.60(8) °), 1 mmol (chloromethyl)cyclopropane) gives 70% 1b after 1 h
whereas the phenyl ketone (1i) has a wider P-C-P bond angle and 98% 1b after 6 h i.e. results that are comparable to those
at 105.75(9) °. These P-C-P bond angles are in-line with that of obtained in the absence of a radical clock34 suggesting a non-
DPM35, which is reported as 106.17 °. Enamine 1k has a wider radical mediated reaction. During our reaction monitoring
P-C-P bond angle of 108.53(8) °. It can be surmised that these studies a small quantity of the E-vinyl phosphine moiety is
crystal data indicate that our hydrofunctionalization products observed by in situ NMR spectroscopy after 1 h suggesting that
are primed for use as ligands in transition metal complexes.
this is the (sterically driven) product of the first
hydrophosphination and the Michael accepting properties of
2 | J. Name., 2012, 00, 1-3
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this phosphinoalkene then facilitate the regioselective second d do no undergo H/D exchange in the absence of KHMDS.
hydrophosphination reaction. To further investigate the role of Given the acidity of the propargylic proton, we believe that
the base, ethyl propiolate-d was used in a catalytic reaction. competitive deprotonation of this moiety takes place which
Deuterium is observed at both the methine and methylene can lead to deuteration of both methylene and methine
positions of 1b-d. Order of addition of reagents/catalyst do not carbons (Scheme 3).
appear to impact on the reaction. HPPh2 and ethyl propiolate-
Scheme 3. Results of deuterium labelling study and proposed catalytic cycle, with potential route by which deuteration could occur at the methylene position (right
hand cycle).
By changing the phosphine to a primary phosphine (H2PPh), form (2f, 2f’ and 2f’’). Mixtures of this type are not observed
we are able to exclusively afford divinylphosphines in the Z,Z with the other aryl substrates. All products are obtained in
configuration, with only one exception (Scheme 4). P,P-divinyl near quantitative spectroscopic yield (>95%) and that loss of
phosphines have only previously been reported by Issleib using product occurs due to the sensitivity of these vinyl phosphines.
the potassium salt of phenylphosphine and appeared to give a
mixture of isomers,29 or by Kobayashi who used AIBN but
Conclusions
In summary, we have presented a mild and rapid route to
obtained a mixture of isomers (52% Z,Z, 30% Z,E and 18%
E,E).36 More recently Takahashi used cross-coupling, rather
highly functionalized 1,1-diphosphines. NaOtBu, as an
inexpensive and easy to handle base, can be used to transform
simple propiolates into their 1,1-diphosphine congeners, with
a high yield achieved even at 1 mol% loading. However,
KHMDS is necessary for more challenging substrates. A change
in phosphine reagent from diphenylphosphine to
phenylphosphine results in a change in reactivity, allowing the
selective formation of P,P-divinylphosphines. Both sets of
products offer intriguing potential modes of reactivity: we
envisage using some of our 1,1-diphosphines as bifunctional
ligands for heterobimetallic complexes, whilst our
divinylphosphines give facile access to monomers for the
preparation of phosphorus-containing polymers. Both of these
aspects are currently under investigation in our laboratory.
than a hydrofunctionalization approach, employing phenyl-
and n-hexyl-vinylzirconocene reagents (where the E-geometry
was predefined) and dichlorophenylphosphine to afford the
E,E divinylphosphine product.37 The transformation we report
here complements the Zr-catalyzed method of Waterman,
whereby internal alkynes undergo mono-hydrophospination
with H2PPh to yield a mixture of E- and Z-vinylic secondary
phosphine or with a prolonged reaction time, the 1,2-
diphosphinoalkane.38
In contrast to our chemistry with HPPh2 (vide supra), the
KHMDS catalyzed transformation with H2PPh is limited to aryl
acetylenes: when propiolates are employed complex mixtures
form of what appears to be polymeric material. Phenyl
acetylene and 4-tert-butylphenylacetylene react well, giving
products 2a and 2b in high isolated yield. Crystals of 2a could
be isolated and display carbon-carbon double bonds of
1.327(4) Å and 1.334(3) Å for C7-C8 and C15-C16 respectively
and a C7-P1-C15 bond angle of 102.4(1) ° (Figure 2).
Conflicts of interest
There are no conflicts to declare.
Phenyl rings substituted with electronically challenging groups
selectively give the targeted products (2c and 2d). When a
highly electron withdrawing 4-trifluoromethyl group is
introduced to the aromatic ring a mixture of E- and Z-products
Acknowledgements
xx
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A homologous series of 1,1-diphosphines have been prepared by alkyne hydrophosphination using
catalytic KHMDS at room temperature.