A bench-stable copper photocatalyst for the rapid hydrophosphination of activated and unactivated alkenes

Article abstract of DOI:10.1039/d0cc06570f

Cu(acac)2 (1) is a highly active catalyst for the hydrophosphination of alkenes. Photocatalytic conditions are critical, and provide high conversions with unactivated substrates that have never before been reported with an air-stable catalyst or at ambient temperature. The commercial availability, ease of use, and broad substrate scope of compound 1 make hydrophosphination more available to synthetic chemists.

Full text of DOI:10.1039/d0cc06570f

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A bench-stable copper photocatalyst for
the rapid hydrophosphination of activated
Cite this:DOI: 10.1039/d0cc06570f
and unactivated alkenes†
Received 1st October 2020,
Accepted 21st October 2020
Steven G. Dannenberg
and Rory Waterman
*
DOI: 10.1039/d0cc06570f
rsc.li/chemcomm
Cu(acac)2 (1) is a highly active catalyst for the hydrophosphination commercially available, air-stable, and base metal hydrophos-
of alkenes. Photocatalytic conditions are critical, and provide phination catalyst.
high conversions with unactivated substrates that have never
Copper is a desirable metal due to its recyclability, relative
before been reported with an air-stable catalyst or at ambient abundance, low toxicity, and the air- and water-stability of many
temperature. The commercial availability, ease of use, and broad precursors.13 Additionally, copper has a rich photochemistry.14,15
substrate scope of compound 1 make hydrophosphination more Our group has observed improved hydrophosphination reactivity
available to synthetic chemists.
upon irradiation with Zr,10,16,17 Fe,18,19 and Ru20 catalysts.
Based on the literature, we identified Cu(acac)2 (1) as an
Metal-catalyzed hydrophosphination is a powerful tool in still- ideal candidate for study. Hydrophosphination with copper has
challenging P–C bond formation because of the ubiquity been performed with a range of copper salts21–23 and by copper
of alkene substrates1 and potential for perfect atom economy coordinated by N-heterocyclic carbene (NHC)24,25 and phosphine26
of the transformation.2 Indeed, phosphines are integral ligands. Additionally, Beletskaya demonstrated compound 1 to be
molecules in organic synthesis and catalysis and are of impor- effective for the addition of phosphorus(V) substrates to alkynes.27
tance in materials science and biologically active molecules.3 Indeed, several groups have found 1 to be more effective at C–H
However, one of the limitations to more widespread use of amination reactions than other copper salts.28,29
hydrophosphination is that many catalysts are air- and/or
water-sensitive, are complicated to prepare, or suffer from
limited substrate scope or modest activity.4–7 Catalysts that
are not readily available and easy to use do not augment the
synthetic chemist’s toolbox.8
A broadly applicable catalyst is one that also addresses some
of the outstanding challenges of hydrophosphination.4 For
example, unactivated alkene substrates remain underutilized
in hydrophosphination. Attempts to use these substrates
have shown limited success,9–11 with few previous reports of
greater than 50% conversion. These have required air-sensitive
catalysts, and elevated temperatures9,11 or high intensity
irradiation (Chart 1).10
Despite advances in activity,12 catalysts for hydrophosphina-
tion in routine synthesis require readily available, inexpensive
catalysts that have established reactivity with a wide range of
substrates. Therefore, we set out to search for a highly active,
Department of Chemistry, University of Vermont, Burlington, Vermont 05405-0125,
USA. E-mail: rory.waterman@uvm.edu
† Electronic supplementary information (ESI) available: Experimental proce-
Chart 1 Examples of intermolecular hydrophosphination catalysts that
are reported to have greater than 50% conversion with unactivated
alkenes.
dures, compound characterization data, supplementary figures and tables, and
photographs and description of the photocatalysis reactor. See DOI: 10.1039/
d0cc06570f
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This analysis led to the general hypothesis that highly irradiation (eqn (2)). When para-substituted styrene substrates were
successful hydrophosphination reactivity can be achieved by treated with 1 equiv. of diphenylphosphine, the tertiary phosphine
employing 1 as a pre-catalyst. This hypothesis has borne out, products were formed in good to excellent yields in under 5 h.
and herein is reported the substantial activity of 1 under low
intensity 360 nm irradiation at ambient temperature. This
overall high activity is accompanied by a significant substrate
scope of alkenes and alkynes. The hydrophosphination activity
of 1 rivals or surpasses the activity of reports with any catalyst,
under any reaction conditions. In this regard, 1 achieves the
aim of an easy-to-use, highly active, and readily available
hydrophosphination catalyst.
(2)
Under these conditions, it was not empirically obvious that
either electron donating or withdrawing substituents promote
the reaction for either phenyl- or diphenylphosphine.
Hydrophosphination of styrene was examined first due to its
common use in recent studies.23,30–33 A chloroform-d1 solution
of styrene was treated with 2 equiv. of phenylphosphine in the
presence of 5 mol% of 1 (eqn (1), see ESI† for optimization).‡
The mixture was irradiated with a broad wavelength 9-W UV/A
lamp (commercial germicidal lamp: see ESI† for details) at
ambient temperature for 20 min, resulting in complete conver-
sion of styrene as measured by 1H NMR spectroscopy and 91%
selectivity for the anti-Markovnikov, single activation product
PhPHCH2CH2Ph as determined by 31P{1H} NMR spectroscopy.
Reactions with primary phosphines are often run with excess
phosphine to minimize the double activation product, and
indeed, small amounts of the tertiary phosphine with similarly
limited amounts of 1,2-diphenyldiphosphine were observed.
These byproducts and catalyst were readily separated by chro-
matography, in a glovebox, to afford isolated product in 66%
yield. Isolation of pure phosphine products from these reac-
tions is well established23,34,35 and not the subject of this
investigation. The use of a glovebox for the handling of primary
phosphine starting materials and isolation of P(III) products
remains a limitation to still more general use of hydropho-
sphination.
Unactivated alkenes, a significant challenge,4 were screened
next and found to be good substrates for this system. Treat-
ment of 1-hexene with 2 equiv. of phenylphosphine and 5 mol%
of 1 gave greater than 70% conversion to the single activation,
secondary phosphine product when monitored by 31P{1H} and
1H NMR over 7 h (eqn (3)) and 80% after 20 h (Table 1, 3a). A
control reaction under identical photocatalytic conditions but
in the absence of 1 exhibited less than 3% conversion over 24 h
and demonstrates the importance of 1.
(3)
To date, this is the fastest report of hydrophosphination of
an unactivated alkene substrate with a primary phosphine.10,36
The only other report with a comparable activity is with
zirconium under photolysis from a higher intensity 253.7 nm
Hg arc lamp for 24 h operating at 400 W (vs. 9 W for this
reaction).10
Treatment of 1-hexene with diphenylphosphine and 5 mol%
of 1 under irradiation at 360 nm in chloroform-d1 gave 25%
conversion of phosphine to a mixture of products after 24 h.
However, irradiation of a neat mixture of 1-hexene, and increasing
to 3 equiv. of diphenylphosphine, and 5 mol% of 1 for 24 h
(1)
Continuous irradiation throughout the reaction is necessary
for accelerated catalysis (see ESI† for details). However, the
reaction does proceed under ambient light. Reactions with
2 equiv. of phenylphosphine and styrene and 5 mol% of 1
under ambient light and temperature proceeded to completion
over the course of 7 h and to 90% conversion over 75 min at 60 1C.
para-Substituted styrenes bearing electron withdrawing
groups or donating substituents were also amenable to these
conditions and converted to the respective secondary phos-
phine product in 490% in 25 min when treated with 2 equiv. of
phenylphosphine under 360 nm (eqn (1)).
Table 1 Hydrophosphination of unactivated alkenes with 1
Initial screening also demonstrated that secondary phos-
phines are also viable substrates. Treatment of styrene and Conversions determined by integration of 1H and 31P{1H} NMR spectra.
a
All runs with 5 mol% of 1. 0.38 mmol unsaturated substrate and
1 equiv. of diphenylphosphine with 5 mol% of 1 resulted in
b
0.76 mmol PhPH2 cin 0.6 ml CDCl3. Neat; 0.114 mmol 1-hexene and
85% conversion to Ph2PCH2CH2Ph (2) after 5 h of 360 nm
3 equiv. of Ph2PH. Neat; 0.38 mmol unsaturated substrate and 3 equiv.
irradiation and 95% conversion was observed after 24 h of of Ph2PH.
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resulted in 64% conversion to product 3b as determined by
Several other unsaturated substrates were also tested. Reac-
1H and 31P{1H} NMR spectroscopy. Improved hydrophosphina- tion of 2,3-dimethyl,1-3-butadiene afforded the 1,4-addition
tion under neat conditions has also been observed in other product within 80 min with phenylphosphine (4d) and 8 h with
studies.18,36,37 Yet more optimization is possible.
1 equiv. diphenylphosphine (4e) under photocatalytic condi-
Despite the more modest reactivity of 1-hexene with Ph2PH, tions with 5 mol% of 1. A strained internal alkene, norbornene,
there remains only one catalyst that can rival its speed.9 gave 96% conversion with 2 equiv. of phenylphosphine (4f). All
However, 1 is desirable because it is air stable, commercially Michael acceptors tested reacted rapidly with both phenyl- and
available, and is active at ambient temperatures. Additionally, diphenylphosphine (4g–j). Initial NMR spectra obtained before
1 is the only catalyst able to demonstrate greater than 50% irradiation indicated that full conversion methyl acrylate and
conversion with both PhPH2 and Ph2PH.
acrylonitrile had occurred, even when kept in the dark.
Additional aliphatic alkenes were then explored. Treatment
of terminal alkenes such as 1-heptene, and 1-octene with
2 equiv. of phenylphosphine and 5 mol% of 1 both gave greater
than 70% conversion to the single activation, secondary phos-
phine product when monitored by 31P{1H} and 1H NMR over
16 h at 360 nm (products 3c–d). Reaction of ethoxy ethene
with phenylphosphine gave 82% conversion to product 3e in
6 h, the fastest and highest conversion observed to date.10
When 1 equiv. of diphenylphosphine was used with ethoxy
(4)
Treatment of internal and terminal alkynes under irradia-
ethene under the same conditions, 32% conversion to product tion with either phenyl- or diphenylphosphine provided access
3f was achieved after 24 h. This could be improved under neat to vinyl phosphine products 5a–c (eqn (4), see ESI† for addi-
conditions with 3 equivalents of diphenylphosphine, in which tional alkyne substrates and conditions). Reaction of 1-phenyl-
in 70% conversion to product 3f occurred after 24 h of irradia- 1-butyne with 1 equiv. of phenylphosphine and 5 mol% of 1
tion. Similarly, allyl benzene was converted in 74% to product under 360 nm irradiation for 24 h afforded the vinyl phosphine
3g after 16 h with 2 equiv. of phenylphosphine and 55% with product in 81% conversion with 100% selectivity for P–C bond
diphenylphosphine to product 3h under the neat conditions formation at the alkyl substituted position and a 3: 1 preference
described above. Allyl chloride is an uncommon hydropho- for the Z-isomer. Reaction with 2 equiv. of phenylphosphine
sphination substrate, and this reaction proceeds to 63% con- under the same conditions afforded the vinyl phosphine product
version to 3i, which illustrates the functional group tolerance of in nearly quantitative conversion and 2.45: 1 selectivity but led to
this catalyst.
More sterically encumbered substrates are accessible in this after 72 h and this reaction was not pursued further.
system as well (Table 2). A cis/trans mixture of b-methylstyrene The mechanism of catalysis is still under consideration and
only trace conversion to the double hydrophosphination product
treated with phenylphosphine and 1 under irradiation resulted questions remain about the role of light and the importance of
in 99% conversion and 82% isolated yield in 20 h to previously open shell intermediates. Further experimentation is under-
unreported 4a. Treatment of a-methyl styrene and phenylpho- way. However, preliminary data suggests a Cu(I) phosphido is
sphine with 1 under irradiation resulted in 92% conversion an active intermediate in this catalysis based on several obser-
to 4b in just over 2 h. When a-methyl styrene was treated with vations and experiments.
1.5 equiv. of diphenylphosphine the result was 83% conversion
after 20 h of irradiation (4c).
Acetylacetone is visible in the 1H NMR spectrum and 1,2-
tetraphenyldiphosphine is observed in the 31P NMR spectrum
of catalytic reaction mixtures with 1. Treatment of 5 mol% of
1 with Ph2PH in the absence of alkene results in the gradual
formation of 2 equiv. of acetylacetone and one half an equiva-
lent (per Cu) of 1,2-tetraphenyldiphosphine. The solution
behavior of this reaction is consistent with [(Ph2PH)CuPPh2]n
previously reported by Caulton38 and other Cu phosphido
compounds in the literature (see ESI† for details).39,40
Table 2 Hydrophosphination of disubstituted and activated alkenes
As a proxy for Cu(I), we tested the activity of [(PPh3)CuH]6 (6)
in these reactions (eqn (5)), knowing that stoichiometric
reaction of 6 with Ph2Ph affords (PPh3)CuPPh2.38 The activities
of 1 and 6 are very similar, suggesting that a Cu(I)-phosphido
may be active in the catalysis. Although a radical mechanism
cannot be ruled out, the formation of Cu(I) indicates that a two-
electron process is a viable, if not the predominant reaction
pathway. With this insight, and because nucleophilic attack
on an unactivated alkene can be dismissed, a catalytic cycle is
proposed in Scheme 1.
Conversions determined by integration of 1H and 31P{1H} NMR spectra.
Reactions conducted in 0.6 ml CDCl3, with 5 mol% of 1 and 0.38 mmol
a
b
c
of alkene. 2 equiv. PhPH2. Isolated yield. 1.5 equiv. Ph2PH and
d
e
0.25 mmol alkene. 1 equiv. Ph2PH. Ambient light.
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‡ In an N2 filled dry box, phosphine, unsaturated substrate, and 1 were
mixed in 0.6 mL of CDCl3 (where applicable) and transferred to an NMR
tube. For neat reactions, 1 and substrates were added directly to a J-
Young NMR tube. After an initial 1H and 31P{1H} NMR spectra, the NMR
tube was placed in the photoreactor and monitored by 1H and 31P{1H}
NMR spectroscopy. The photoreactor temperature was 25–30 1C. See
ESI† for further details.
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