Photocatalytic Arylation of P4 and PH3: Reaction Development Through Mechanistic Insight

Article abstract of DOI:10.1002/anie.202110619

Detailed ³¹P{¹H} NMR spectroscopic investigations provide deeper insight into the complex, multi-step mechanisms involved in the recently reported photocatalytic arylation of white phosphorus (P₄). Specifically, these studies have identified a number of previously unrecognized side products, which arise from an unexpected non-innocent behavior of the commonly employed terminal reductant Et₃N. The different rate of formation of these products explains discrepancies in the performance of the two most effective catalysts, [Ir(dtbbpy)(ppy)₂][PF₆] (dtbbpy=4,4′-di-tert-butyl-2,2′-bipyridine) and 3DPAFIPN. Inspired by the observation of PH₃ as a minor intermediate, we have developed the first catalytic procedure for the arylation of this key industrial compound. Similar to P₄ arylation, this method affords valuable triarylphosphines or tetraarylphosphonium salts depending on the steric profile of the aryl substituents.

Full text of DOI:10.1002/anie.202110619

A Journal of the Gesellschaft Deutscher Chemiker
Angewandte
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International Edition
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Accepted Article
Title: Photocatalytic Arylation of P4 and PH3: Reaction Development
Through Mechanistic Insight
Authors: Robin Rothfelder, Verena Streitferdt, Ulrich Lennert, Jose
Cammarata, Daniel J. Scott, Kirsten Zeitler, Ruth M.
Gschwind, and Robert Wolf
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To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.202110619
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10.1002/anie.202110619
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RESEARCH ARTICLE
Photocatalytic Arylation of P4 and PH3: Reaction Development
Through Mechanistic Insight
Robin Rothfelder,[a] Verena Streitferdt,[b] Ulrich Lennert,[a] Jose Cammarata,[a] Daniel J. Scott,[a] Kirsten
Zeitler,[c] Ruth M. Gschwind,*[b] and Robert Wolf*[a]
[a]
R. Rothfelder, J. Cammarata, Dr. U. Lennert, Dr. D. J. Scott, Prof. Dr. R. Wolf
Institute of Inorganic Chemistry
University of Regensburg
93040 Regensburg, Germany
E-mail: robert.wolf@ur.de
[b]
[c]
Dr. V. Streitferdt, Prof. Dr. R. M. Gschwind
Institute of Organic Chemistry
University of Regensburg
93040 Regensburg, Germany
Prof. Dr. K. Zeitler
Institute of Organic Chemistry
University of Leipzig
04103 Leipzig, Germany
Supporting information for this article is given via a link at the end of the document.
Abstract: Detailed 31P{1H} NMR spectroscopic investigations provide
which find important commercial applications in catalysis (among
many other areas) and whose preparation involves such
deeper insight into the complex, multi-step mechanisms involved in
the recently reported photocatalytic arylation of white phosphorus (P4). compounds as Cl2, PCl3 and molten Na (Figure 1a).[4,5]
Specifically, these studies have identified a number of previously
unrecognized side products, which arise from an unexpected non-
innocent behavior of the commonly employed terminal reductant Et3N.
The different rate of formation of these products explains
discrepancies in the performance of the two most effective catalysts,
[Ir(dtbbpy)(ppy)2][PF6] (dtbbpy = 4,4′-di-tert-butyl-2,2′-bipyridine) and
These deficiencies have prompted great interest in the
development of alternative methodologies for the transformation
of P4,[6] and particularly those that have the potential to furnish
OPCs directly in a single reaction, without the need for laborious
isolation
and
manipulation
of
potentially
hazardous
intermediates.[7] Unfortunately, despite extensive studies leading
to numerous fundamental insights, the development of such new
reactions has proven exceedingly challenging. In particular, while
P4 is well known for being chemically reactive, researchers have
struggled to find reactions that can selectively produce individual,
useful OPCs in good yield.[8]
3DPAFIPN. Inspired by the observation of PH3 as
a minor
intermediate, we have developed the first catalytic procedure for the
arylation of this key industrial compound. Similar to P4 arylation, this
method affords valuable triarylphosphines or tetraarylphosphonium
salts depending on the steric profile of the aryl substituents.
Recently, we reported a breakthrough in this area. We found that
photoredox methods could be employed to successfully combine
P4 with aryl iodides (ArI) to generate the corresponding Ar3P and
Ar4P+ products under very mild conditions, often with markedly
high selectivity (Figure 1b).[9] This is the first example of such a
catalytic procedure furnishing these products directly from P4.
Given the exponential growth in photoredox techniques reported
over the past decade,[10] including for P–C bond formation in other
contexts,[11] photoredox catalysis may also hold a much broader
potential for the productive transformation of P4.[12] Nevertheless,
if this goal is to be successfully realised it is crucial to develop a
deeper understanding of the mechanisms that underpin the
existing photoredox reactivity of P4.[13]
Herein we report a detailed NMR spectroscopic study on the
mechanism of photoredox-catalytic P4 arylation. From the results,
we have been able to draw a number of significant conclusions.
These include a recognition of the importance of side reactions in
determining overall product yields, a rationalisation for the
differing activities of precious metal and organic photocatalysts,
and the identification of a viable minor reaction pathway that
involves PH3 as an early reaction intermediate. Building upon the
Introduction
White phosphorus (P4) is the common precursor from which all
organophosphorus compounds (OPCs) are currently prepared.[1]
The enormous range of important applications of these
compounds
(including
pharmaceuticals,
agrochemicals,
photoinitiators, catalysts, et cetera) makes P4 one of the most
important single precursors for the modern chemical industry.[2]
Unfortunately, current methods for the use of elemental
phosphorus suffer from major drawbacks, including difficulties in
the initial preparation of P4 from phosphate minerals as well as
problems relating to phosphorus recovery and recycling.[3]
Particularly significant are serious limitations in state-of-the-art
methods for the transformation of P4 into useful OPCs, which rely
on wasteful and inefficient multi-step procedures involving
extremely hazardous and difficult-to-handle reagents and
intermediates.[4] These problems are exemplified in the syntheses
of arylated phosphines (Ar3P) and phosphonium salts (Ar4P+),
1
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last of these, we have been able to develop the first examples of
catalytic arylation of PH3, so providing an entirely new route to
produce Ar3P and Ar4P+ products starting from this industrially
important synthetic intermediate (Figure 1c).
Et3N, presumably via direct abstraction of H● (HAT) or H+ following
oxidation to Et3N●+. As part of the study described herein it was
possible to confirm this hypothesis through use of deuterium-
labelled Et3N-d15, which led to clear deuterium incorporation into
these intermediates (see Section 3.6 of the Supporting
Information for further details). Subsequent loss of these H atoms
was proposed to proceed by formation of ArH (observed as a
byproduct by 1H and 2H NMR spectroscopy).[14]
Each of the individual arylation steps (v-viii) was previously
confirmed to be photocatalytic. Indeed, in a recent follow-up study,
we reported that the same methodology could be optimised to use
PhPH2 and Ph2PH as starting materials for the generation of
+
+
unsymmetrically substituted products (e.g. PhPAr3 , Ph2PAr2 ;
Scheme 1b).[9b] This report also showed that the previously used
precious metal catalyst [1]PF6 could be replaced by the
inexpensive and easily accessible organic catalyst 3DPAFIPN (2;
structure shown in Scheme 1) for the arylation of both P4 and
PhPH2/Ph2PH.[15]
Figure 1. (a) Indirect, stepwise methods for the synthesis of triarylphosphines
Ar3P and tetraarylphosphoniums Ar4P+ employed industrially; (b) recently
reported direct photocatalytic transformation of P4 into Ar3P and Ar4P+ and (c)
direct photocatalytic arylation of PH3 described herein, developed based on
improved mechanistic understanding of P4 arylation.
Results and Discussion
Previous studies and open mechanistic questions
As part of our initial report of photoredox-catalysed P4 arylation
we described a series of preliminary mechanistic studies, on the
basis of which we were able to propose an approximate outline
mechanism for the catalytic phenylation of P4 to Ph4P+.[9a] This is
reproduced in Scheme 1a, and involves a fairly typical photoredox
catalytic cycle for the generation of phenyl radicals (Ph●), in which
the photoredox catalyst [1]PF6 (1 = Ir(dtbbpy)(ppy)2, dtbbpy = 4,4′-
di-tert-butyl-2,2′-bipyridine, ppy = 2-(2-pyridyl)phenyl; structure
shown in Scheme 1) undergoes photoexcitation by blue light,
followed by reductive quenching by Et3N (which acts as terminal
reductant in this reaction), and oxidative regeneration by the
substrate PhI. This last redox step prompts fragmentation of the
aryl halide substrate, generating radicals Ph●. These can then add
to P4 to generate in sequence PhPH2, Ph2PH, Ph3P and Ph4P+,
with the formation of these intermediates being observable by
31P{1H} NMR spectroscopy. The H atoms required for formation
of PhPH2 and Ph2PH were proposed to derive from the reductant
Scheme 1. (a) Outline mechanism for photocatalytic P4 arylation proposed
previously; and (b) recently reported photocatalytic P–H arylation of PhPH2 and
Ph2PH.
Despite the superficial simplicity of the catalytic cycle shown in
Scheme 1a it is clear that the overall mechanism is highly complex
2
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(we have emphasised previously that exhaustive phenylation of
one equivalent of P4 requires the cleavage of six separate P—P
bonds, formation of 16 new C—P bonds, and consumption of at
least 16 equivalents each of PhI and Et3N) and that several
important questions remain to be answered. From among these,
at the outset of this study we identified three that are of particular
significance:
1) Is it possible to identify any other intermediate(s) formed prior
to PhPH2? Although PhPH2 is the first P-containing intermediate
that it has been possible to observe during the phenylation of P4
thus far, it clearly cannot be the first such intermediate. Notably,
by identifying PhPH2 and Ph2PH as intermediates it has been
possible to develop new functionalisation reactions of these
substrates,[9b] which might also be true for any earlier
intermediates.
others (designated Side1-Side5) were identified as side-products
and were persistent until the end of the reaction (Figure 2a). The
same side-products (Side1-Side5) could also subsequently be
detected in the reaction catalysed by [1]PF6, but at appreciably
lower concentrations (Figure 2b). Nevertheless, the combined
intensity of these signals accounts for a significant proportion of
the overall 31P intensity in the final reaction spectra, and it seems
feasible that there may be further unresolved signals of lower
intensity, which could sum to a further significant value (vide infra).
2) Is it possible to account for missing 31P intensity in these
reactions? Preliminary in situ 31P{1H} NMR monitoring has shown
that initial consumption of P4 is far faster than the formation of the
first observable P-containing intermediate (PhPH2). Similarly,
standard 31P{1H} spectroscopic measurements of the final
reaction mixtures suggest that formation of the target products
(e.g. Ar3P, Ar4P+) is typically very clean (no other P-containing
species present, including P4), yet conversion to these products
is consistently less than quantitative based on the initial amount
of P4.
3) Can discrepancies in performance between catalysts [1]PF6
and 2 be explained? Although their photoredox properties are
very similar, [1]PF6 has been found to give consistently higher
product conversions for P4 arylation than 2. Conversely, 2 has
been found to provide better conversions than [1]PF6 for
analogous arylations starting from PhPH2/Ph2PH.
Identifying new intermediates and side-products during the
arylation of P4
Having previously shown 31P{1H} NMR monitoring to be a
valuable tool for the investigation of the P4 arylation reaction,[9a]
we reasoned that answers to our question set might be found
through more detailed NMR spectroscopic analysis. For
consistency with previous studies, arylation using PhI was again
chosen as the simplest model system. To begin, the phenylation
of P4 using organic photocatalyst 2 was monitored over time, to
provide a comparison with the analogous experiment already
performed using [1]PF6 as catalyst.[9a,16] As expected, a similar
overall reaction profile was observed (Figure 2a), with rapid
consumption of P4 followed by intermediate formation of PhPH2,
Ph2PH and Ph3P, and ultimately formation of Ph4P+ as the major
reaction product. Observation of a photo-CIDNP effect in the
corresponding 1H NMR spectra was also consistent with previous
observations using [1]PF6 (see Section 3.8 of the Supporting
Information for more details).[9a,17] Nevertheless, some qualitative
differences between the two catalysts could clearly be resolved.
In particular, formation of the early intermediates PhPH2 and
Ph2PH appears to peak significantly more quickly using 2, while
the magnitude of these peaks is reduced (c.f. Figure 2a,b).
More dramatically, in addition to the expected intermediates
PhxPH (x = 1-3), 31P{1H} NMR monitoring clearly showed the
Figure 2. Reaction profiles showing the evolution of P atom speciation during
the light-driven phenylation of P4 (0.1 mmol scale) catalysed by 2 (a) or [1]PF6
(b), as assessed by time-resolved 31P{1H} NMR spectroscopy. Equivalents of
reagent (equiv.) and catalyst loadings (in mol%) are defined per P atom.
(unprod.) indicates the sum of intensities for unproductive side-products
Side1-Side5. For a more comprehensive display of the kinetics see Section
3.9.1 in the Supporting Information.
These observations suggest a clear explanation for less-than-
quantitative target product formation highlighted above, with
maximum formation of the final target products being limited by
the formation of a collection of minor side products in amounts
that are individually insignificant, but collectively substantial.
Moreover, the fact that far greater amounts of these side-products
are observed when using the organocatalyst 2 provides a
rationale for the observation that 2 provides consistently poorer
final product conversions for the arylation of P4, despite being a
x
3-
formation of a significant number of other minor peaks during the
reaction catalysed by 2 (for representative example spectra, see
Figure 3a). Some of these (designated Int1-Int4) were identified
as intermediate species (either for productive or unproductive
processes) based upon their concentration profile over time, while
3
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10.1002/anie.202110619
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RESEARCH ARTICLE
more productive catalyst for the optimised synthetic arylations of
dimerization of transiently-formed radicals Ph2P●).[9b] Given that
Et3N is widely used as a ‘privileged’ terminal reductant in
photoredox transformations, and that [1]PF6 and 2 have also been
used to catalyse many other photoredox reactions, these results
suggest that similar patterns of non-selective side-reactivity could
be an underappreciated but highly significant limiting factor in
many other photoredox transformations (indeed, related non-
innocent side reactions have previously been highlighted in some
the ‘downstream’ intermediates PhPH2 and Ph2PH (for
a
discussion of catalyst performance in these latter reactions see
Section 3.9.3 of the Supporting Information).
other catalytic reactions).[18] In the absence of the convenient 31
P
NMR handle, these would likely be extremely challenging to
detect. Minimisation of these side reactions is a clear avenue for
further reaction optimisation.[19]
To try and identify further reaction intermediates – particularly
those that may form in the early stages on the reaction –
additional monitoring experiments were carried out on reactions
performed at lower temperatures and using higher catalyst
loadings. It was anticipated that transient, early intermediates
might be able to better accumulate under these conditions and,
indeed, several further 31P{1H} resonances could be observed
(see Figure 4a; designated Int5-Int8; again, these may be
intermediates for either productive or unproductive processes),
and plausible corresponding chemical structures assigned are
depicted in Figure 4b (see also Section 3.11.1 of the Supporting
Information). The proposed structures of Int5-Int7 further
emphasise the non-innocent behaviour of the Et3N reductant.
Figure 3. Example 31P{1H} NMR spectra showing the formation of minor
intermediates (Int1-Int4) and side-products (Side1-Side5) during the light-
driven phenylation of P4 (0.1 mmol scale) catalysed by organocatalyst 2 (a); and
tentatively proposed structures of these species based on in situ NMR data (see
Sections 3.10 and 3.11 of the Supporting Information for more information) (b).
Figure 4. (a) 31P{1H} NMR spectrum showing the formation of further
intermediates (Int5-Int8) of the light-driven phenylation of P4 (0.1 mmol scale)
catalysed by [1]PF6. The spectrum was recorded in the dark after an illumination
period of 30 min at 273 K (see also Section 3.11.1 of the Supporting
Information). (b) Proposed structures of Int5-Int8 observed during the light-
driven phenylation of P4 catalysed by [1]PF6 and 2 at low temperatures and high
catalyst loadings.
Plausible structures of the species Int1-Int3 and Side1-Side5 are
shown in Figure 3b and are based upon detailed in situ NMR
studies including 2D techniques and proton-coupled 31P spectra
which are presented in the Supporting Information (Sections 3.10
and 3.11), alongside discussion of possible mechanisms of
formation. As an illustrative example, the product Side1 could be
assigned based on a combination of its 31P chemical shift
(suggestive of a Ph2PNR2 species), long range 1H-31P correlation
experiments (showing correlations between the 31P resonance
and 1H signals at chemical shifts consistent with Ph and CH2Me
peaks), and comparison with literature data.
Interestingly, the majority of these species appear to be derived
from non-innocent behaviour of the Et3N terminal reductant (with
the notable exception of Int3, Ph4P2, which was also observed in
our previous investigation of the 2-catalysed reaction of Ph2PH
with cyclohexyl iodide, and was proposed to arise through
PH3 as a substrate for photocatalytic arylation
The specific observation of PH3 as one of the above intermediate
signals (Int8; readily assigned on the basis of its characteristic
chemical shift and binomial quartet splitting in the proton-coupled
31P spectrum, see Figure 4a) was particularly intriguing.[3b]
Although our previous mechanistic proposals (e.g. Scheme 1a)
had assumed PhPH2 to be the first P1 intermediate formed, this
result – combined with our previous observation that PH3 can be
formed upon irradiation of a combination of P4, Et3N and [1]PF6 in
the absence of ArI – suggested an alternative synthetic possibility.
4
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Specifically, it was queried whether PH3 could in fact be a key
intermediate formed prior to arylation: i.e. whether arylation of P4
could proceed via initial Et3N-mediated reduction to PH3,[20] with
arylation only subsequently occurring. Notably, such a possibility
would have broad implications beyond the immediate mechanistic
significance. PH3 is a major synthetic intermediate, employed
industrially for the preparation of many important phosphine and
phosphonium derivatives. However, these syntheses proceed
exclusively through the hydrophosphination of unsaturated
substrates, which limits the scope of accessible products and
thereby excludes the formation of aryl-substituted derivatives
(Ar3P, Ar4P+). Indeed, efficient, direct arylation of PH3 remains a
long-unmet synthetic goal that, though related, is distinct from the
target of direct P4 functionalisation.[3c,4,21]
necessary to achieve appreciable product formation (Table S1).
Catalytic formation of Ph4P+ could also be achieved using
organocatalyst 2 instead of [1]PF6 (Table 1, entry 2), illustrating
that this reactivity is not dependent on the use of a precious metal,
and is mechanistically feasible for an organocatalysed reaction.
Conversion to the target Ph4P+ could be significantly increased
through modification of the reaction time, solvent, and
concentration (Table 1, entry 3 and Table S2). Although these
conversions are still appreciably lower than those obtained
previously when starting from P4, this may be attributable at least
in part to differences in experimental setup. In particular, the need
for gaseous PH3 to diffuse between reaction chambers before
dissolving in the reaction solution is expected to significantly
impact the rate of reaction. This conclusion was supported by
reactions performed using a two-chamber apparatus of reduced
volume, which led to a further improvement in performance (Table
1, entry 4; for full details of the apparatus see Section 2.1 of the
Supporting Information). An additional improvement was
observed upon replacement of Zn3P2 with NaPH2, as an
alternative source of PH3 upon acidification (Table 1, entry 5).[23]
To this end, it was decided to investigate the deliberate use of PH3
as
a
substrate for our photoredox-catalysed arylation
methodology. For reasons of practical simplicity, PH3 was not
employed directly, but rather generated in situ using a two-
chambered apparatus, inspired by a recent report by Ball et al.
(Figure 5).[22] Addition of aqueous HCl to solid Zn3P2 in one
chamber liberates gaseous PH3, which can diffuse into the
second chamber. This chamber contains the remaining
components of the photocatalytic reaction mixture and is stirred
under continuous blue LED irradiation (with concomitant water
cooling to maintain approximately ambient temperature).
Table 1. Photocatalytic phenylation of PH3.
Entry[a]
PH3
source
(mmol)
PC
(mol%)
t / h
Solvent
Conversion
to Ph4P+
/ %
1
2
Zn3P2
(0.05)
[1]PF6
(2)
18
48
48
48
24
24
24
MeCN/PhH
(3:1)
17
23
30
35
41
29
68
Zn3P2
(0.15)
2
(10)
MeCN/PhH
(3:1)
3
Zn3P2
(0.15)
[1]PF6
(2)
MeCN
MeCN
MeCN
MeCN
MeCN
4[b]
5[b]
6[c]
7[c][d]
Zn3P2
(0.15)
[1]PF6
(2)
NaPH2
(0.1)
[1]PF6
(2)
NaPH2
(0.1)
[1]PF6
(2)
NaPH2
(0.1)
[1]PF6
(2)
[a] Reactions performed using a 20 mL two-chambered apparatus described in
Figure 5, using 12.5 equiv. HCl, 11 equiv. PhI, 14.4 equiv. Et3N in 2.0 mL solvent
under blue LED irradiation and N2 atmosphere. [b] A 10 mL two-chambered
apparatus was used. [c] A 10 mL single-chambered apparatus was used. [d] No
HCl was added. Equivalents of reagent (equiv) and catalyst loadings (in mol%)
are defined per P atom.
Figure 5. Schematic representation of the two-chambered apparatus used to
investigate the photocatalytic phenylation of PH3, generated by in situ
acidification of suitable solid precursors.
Gratifyingly, initial experiments using catalytic [1]PF6 and reaction
conditions identical to those used previously in the optimised
phenylation of P4 unambiguously confirmed the formation of
Ph4P+ in modest yields (Table 1, entry 1). This result clearly
illustrates the feasibility of PH3 as an intermediate en route to
arylated products and to our knowledge is the first example of the
successful catalytic arylation of PH3. Control experiments
confirmed that all reaction components ([1]PF6, Et3N, light) were
To further mitigate problems associated with gas transfer of PH3,
the use of a single-chambered experimental apparatus was
pursued, within which it was hoped that addition of acid would
trigger release of PH3 directly into the photocatalytic reaction
solution (for full details see Section 2.2.1 of the Supporting
Information). Disappointingly, use of this apparatus in
combination with NaPH2/HCl as a source of PH3 did not lead to
5
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RESEARCH ARTICLE
an improvement in reaction outcome, although clear catalytic
formation of Ph4P+ was once again observed (Table 1, entry 6).
Gratifyingly, however, when this reaction was repeated in the
absence of HCl significantly improved results were observed, with
very good conversion to the target product achieved following
slight further optimisation (Table 1, entry 7 and Table S3). Thus,
the conjugate base of PH3 appears to be a highly effective and
convenient synthetic surrogate for PH3 in these reactions,
allowing catalytic arylation to be performed in a practically
convenient manner while achieving synthetically relevant
conversion and selectivity.
substrates (notably 2-iodotoluene, which provided good
conversion to the important ligand (o-tol)3P with good conversion
and excellent selectivity; o-tol = 2-methylphenyl; Table 2, entry
2),[5] as well as electron-deficient substrates (such as methyl
4-iodobenzoate; Table 2, entry 7). Notably, the particularly bulky
substrate MesI (Mes = 2,4,6-trimethylphenyl) failed to reach even
the tertiary phosphine, instead producing the primary and
secondary phosphines MesPH2 and Mes2PH as the only products
detected by standard 31P{1H} NMR spectroscopic measurements
(Table 2, entry 15). The heteroatomic substrate Ph3SnCl could
also successfully be employed, providing reasonable, selective
conversion to the interesting “P3-” synthon (Ph3Sn)3P without any
further reaction optimisation (Table 2, entry 16). In all cases the
observed trends in reactivity and selectivity are in excellent
agreement with those noted previously for the photocatalytic
arylation of P4.[9]
Table 2. Photoredox arylation of NaPH2 (as a surrogate for PH3) catalysed by
[1]PF6.
Table 3. Photoredox arylation of NaPH2 (as a surrogate for PH3) catalysed by
organocatalyst 2.
Entry[a]
R
Conversion
to Ar4P+
/ %
Conversion
to Ar3P / %
Conversion
to Ar2PH
/ %
Conversion
to ArPH2
/ %
1
2
H
77
-
-
63
6
-
-
-
-
Entry[a]
R
Conversion
to Ar4P+
/ %
Conversion
to Ar3P / %
Conversion
to Ar2PH
/ %
Conversion
to ArPH2
/ %
2-Me
3
3-Me
61
64
-
-
-
4
4-Me
<5
10
<5
32
13
42
<5
6
-
-
1
2
H
72
-
-
51
<5
-
-
-
-
-
5
2-CO2Me
3-CO2Me
4-CO2Me
2-SMe
2-OMe
3-OMe
4-OMe
2-CF3
-
-
2-Me
6
29
-
-
-
3
3-Me
51
56
-
-
-
7
-
-
4
4-Me
-
-
8
-
-
-
5
2-CO2Me
3-CO2Me
4-CO2Me
2-SMe
2-OMe
3-OMe
4-OMe
2-CF3
7
<5
-
-
9
-
-
-
6
20
-
<5
9
-
10
11
12
13
14
15
16
53
39
-
-
-
7
-
-
-
-
8
-
29
52
7
-
-
-
-
-
9
-
-
-
3-CF3
12
7
7
-
-
10
11
12
13
14
15
16
72
34
-
-
-
4-CF3
19
-
-
-
14
-
-
-
2,4,6-Me3
-
11
-
17
-
-
-
Ph3SnCl
-
55[c]
3-CF3
30
<5
-
6
-
-
[b]
4-CF3
18
-
-
-
[a] Reactions performed using 0.1 mmol NaPH2, 2 mol% [1]PF6, 11 equiv. ArI,
15 equiv. Et3N in 2.0 mL MeCN under blue LED irradiation and N2 atmosphere
for 24 h. [b] Ph3SnCl instead of ArI. [c] (Ph3Sn)3P formed instead of Ar3P.
2,4,6-Me3
7
-
19
-
Ph3SnCl
-
41[c]
[b]
Having identified an optimised set of reaction conditions for the
[1]PF6-catalysed phenylation of PH3, the use of other, substituted
aryl iodides was investigated (Table 2). Satisfyingly, a range of
other substrates ArI could be employed successfully, including
examples bearing both electron-donating and electron-
withdrawing groups and with varying steric bulk. These reactions
yielded either phosphonium salts Ar4P+ or tertiary phosphines
Ar3P, with the latter being favoured for more sterically hindered
[a] Reactions performed using 0.1 mmol NaPH2, 10 mol% 2, 13 equiv. ArI, 16
equiv. Et3N in 2.0 mL MeCN under blue LED irradiation and N2 atmosphere for
24 h. [b] Ph3SnCl used instead of ArI. [c] (Ph3Sn)3P formed instead of Ar3P.
Having established the scope of the [1]PF6-catalysed reaction, the
use of the less expensive and more abundantly available,
sustainable organic photoredox catalyst 2 was also investigated.
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Gratifyingly, after only minor further reaction optimisation (Table
S4), good conversions could also be achieved using this more
practical, precious metal-free catalyst, under similar conditions
(Table 3). In general, both catalysts achieve similar conversions,
and the same trends in product selectivity are observed with
respect to the substrates’ steric and electronic properties.
Nevertheless, in several cases an appreciably superior
preference is observed for either the metallo- or organo-catalyst
(for example: compare entries 2 and 9 in both Table 2 and Table
3), indicating that the choice of catalyst can be tailored to the
specific target product.
respectively by these species from Et3N+• (Et3N having been
established as the ultimate H atom source for this chemistry; vide
supra; for the corresponding in situ NMR study applying fully
deuterated Et3N see Section 3.6 in the Supporting Information)
then generates new P–H bonds and ultimately PH3.
Arylation of PH3 is proposed to occur via an analogous
mechanism to that already established for P–H arylation of the
‘downstream’ intermediates PhPH2 and Ph2PH. Reduction of ArI
by PC●⁻ (generated as outlined above) generates aryl radicals Ar●
●
that can abstract H● to generate transient PH2 which can then
combine with a second equivalent of Ar● to produce ArPH2 (most
likely via intermediate formation of the dimer P2H4; c.f. our
previous observation of Ph4P2 during P–H functionalisation of
Ph2PH).[9b] Analogous, subsequent arylation steps then generate
in turn Ar2PH and Ar3P (and, for certain Ar, Ar4P+), as established
in our previous investigations. Formation of this sequence of
intermediates has been further confirmed by NMR monitoring of
the ‘single chamber’ arylation of NaPH2 (Figure 6).
Figure 6. Reaction profile showing the evolution of P atom speciation during the
light-driven phenylation of NaPH2 (0.1 mmol scale) catalysed by organocatalyst
2, as assessed by time-resolved 31P{1H} NMR spectroscopy. Equivalents of
reagent (equiv.) and catalyst loadings (in mol%) are defined per P atom.
(unprod.) indicates the sum of intensities for unproductive side-products
−
Side1-Side5. In the magnified region, the course of PH2 is highlighted as a
thicker line to emphasise the very low amounts present throughout.
Notably, the reaction profile in Figure 6 shows that only small
−
Scheme 2. Complete proposed mechanisms for the photocatalytic reduction of
P4 to PH3 in the absence of ArI (a); and the photocatalytic arylation of PH3 in the
presence of ArI (b). Here, [P]–[P] indicates a generic P–P bond derived from P4
and [P]–H indicates a generic P–H bond derived from PH3. PC = [1]+ or 2.
amounts of NaPH2 are dissolved at any specific time (PH2 ), and
+
also that the sequential reaction steps leading to PPh4 proceed
very cleanly with nearly no side product formation (c.f. Figure 2
for analogous, less selective reactions starting from P4). Based on
this apparent correlation it was speculated that using lower
concentrations of other monophosphorus starting materials might
also provide cleaner reactions, and thus higher eventual yields.
And indeed, NMR investigations of the light-driven arylation of
H2PPh (applied in different concentrations) confirmed this
hypothesis by showing that the total yield of side products
increases with increasing concentration of starting material,
alongside a concomitant decrease in yield of the final product (for
a more comprehensive discussion of side product formation
during the arylation of PhPH2, see Section 3.9.4 in the Supporting
Information).
Mechanisms of photocatalytic arylation
Based on our prior studies of photocatalytic P4, PhPH2 and Ph2PH
arylation, as well as the studies described herein, it is possible to
propose complete mechanistic courses for both the photocatalytic
formation of PH3 from P4 and Et3N, and the photocatalytic
arylation of PH3 (Scheme 2). For the former, the photoexcited
state of the photocatalyst PC (PC = [1]+ or 2) undergoes reductive
quenching by Et3N (confirmed previously by fluorescence
quenching experiments) to generate Et3N+• and the reduced
catalyst PC•⁻. Thus generated, PC•⁻ can effect single electron
reduction of one of the P–P bonds present in P4 (confirmed
previously by UV-Vis spectroelectrochemistry) to generate a
phosphorus-centred radical and anion. Abstraction of H● and H+
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Competing mechanisms of P4 arylation
quantitative yields of their target products, despite full
consumption of starting material and apparently clean conversion.
Moreover, the use of the organophotocatalyst 2 to mediate these
reactions instead of the iridium catalyst [1]PF6 has been shown to
significantly increase the prevalence of these side products which
provides an explanation for its poorer catalytic performance in P4
arylation, despite other investigations showing it to be a superior
catalyst for the closely related arylation of PhPH2 and Ph2PH.
These side products seem to be primarily derived from
unexpected side reactions of the Et3N reductant (or the aminium,
iminium or enamine oxidation products thereof). Given the
widespread use of Et3N as an electron donor in photoredox
chemistry, these results provide further evidence that similar side
reactions may have an underappreciated limiting effect on
reaction yields for many other transformations. Based on this
realisation, current efforts are being made to replace Et3N with a
‘better-behaved’ combination of reductant and hydrogen source,
to facilitate the desired transformation while minimising undesired
side reactivity.
Alongside this mechanistic insight, based on the detection of PH3
as an additional intermediate, these studies have also enabled
the development of an entirely new photocatalytic transformation.
Specifically, the first examples of the catalytic arylation of PH3
have been developed, which allow for the unprecedented direct
transformation of this key industrial P1 precursor into a sterically
and electronically diverse range of valuable triarylphosphines and
tetraarylphosphonium salts. Notably, this reaction does not
Taken together, the elementary steps outlined above (reduction
of P4 to PH3 and its subsequent arylation) provide a plausible
alternative mechanistic proposal for our previously reported
catalytic arylation of P4. Nevertheless, the mechanistic complexity
of these reactions should again be acknowledged, and several
specific observations suggest that these are unlikely to be the only
kinetically viable elementary mechanistic steps. For example, it
was noted in our original report that upon irradiation in the
presence of [1]PF6 and Et3N, P4 is consumed more quickly in the
presence of PhI than in its absence, with the reverse being
observed for consumption of PhI in the presence/absence of P4.
While the latter trend is easily explained based upon the above
mechanism (since PhI must compete with P4 to react with PC•⁻),
the former is more difficult to account for. Moreover, attempts to
quantify the PH3 formed during the photocatalytic reaction
between P4 and Et3N in the absence of ArI suggest this to be a
rather inefficient process that produces PH3 in only very low yield
(see Section 3.12 of the Supporting Information for full details). It
is therefore likely that reaction with Ph● can provide an alternative
means by which the P–P bonds of P4 are broken (Scheme 3), in
line with our initial mechanistic hypothesis.[24] We thus propose
that initial degradation of the P4 tetrahedron to P1 species can
proceed through a combination of both pathways, to generate a
mixture of PH3 and ArPH2.[25] The relative rates, and hence
importance, of these competing mechanistic routes is likely to
depend strongly on the identity of the arene substrate (for
example, more hindered aryl radicals may add more slowly to P4,
and so render this pathway less competitive).
require
a precious metal catalyst, and works well using
3DPAFIPN as an inexpensive and more sustainable organic
photoredox catalyst.
Acknowledgements
We thank Dr. Gabor Balász (University of Regensburg) for a
generous donation of NaPH2 and Prof. Dr. B. Luy (Karlsruhe
Institute of Technology) for providing the broadband pulse
xyBEBOP. Financial Support by the European Research Council
(ERC CoG 772299), the Deutsche Forschungsgemeinschaft
(CRC 325) and the Alexander von Humboldt Foundation
(postdoctoral fellowship for D.J.S.) is gratefully acknowledged.
Scheme 3. Proposed alternative initial mechanism for the photocatalytic
transformation of P4 in the presence of ArI. Here, [P]–[P] indicates a generic P–
P bond derived from P4.
Keywords: phosphine • white phosphorus • arylation •
photoredox catalysis • NMR spectroscopy
Conclusion
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Detailed NMR spectroscopic studies have been used to provide a
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photocatalytic arylation of P4. Despite the complexity of this
elaborate transformation, it is now possible to propose a plausible
and comprehensive set of elementary steps for this reaction,
supported by experimental observations. In addition to these
primary productive steps, it has been shown that a wide variety of
competing side reactions are relevant to the overall course of the
reaction, resulting in of a large number of minor side products and
intermediates. While these products are present in individually
insignificant quantities they sum to an appreciable fraction of the
overall P-containing reaction products, and their formation
therefore explains the inability of these transformations to provide
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10.1002/anie.202110619
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favoured on steric grounds. For Ar = Ph, direct formation of Ph3P as a
major pathway is also seemingly excluded by the kinetic profiles of these
reactions, which show that initial formation is very slow relative to PhPH2
and Ph2PH. For Ph2PH, which forms more quickly, it is harder to
confidently distinguish between formation as a P1 product directly from
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[19] Note however that previous screening efforts have highlighted the
importance of using a reductant that can also act as a source of H atoms
(presumably to facilitate formation of intermediates including PhPH2 and
Ph2PH), so replacement of Et3N with alternative reductants is a non-trivial
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[23] This may be due to more rapid release of PH3 by NaPH2, leading to
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[24] Indeed, we have previously proposed that P–H alkylation of Ph2PH may
proceed via analogous radical attack on the P–P bond of intermediately-
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Entry for the Table of Contents
31P{1H} NMR spectroscopic studies provide significant, new insights into the mechanism of the recently reported photocatalytic
arylation of white phosphorus (P4). Through the first-time observation of a series of reaction intermediates, these studies have also
inspired the development of the first examples of direct, catalytic arylation of PH3, which is a key synthetic intermediate for industrial
phosphorus chemistry.
Institute and/or researcher Twitter usernames: @TheWolf_Group
10
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