Air- and water-stable Lewis acids: Synthesis and reactivity of P-trifluoromethyl electrophilic phosphonium cations

Article abstract of DOI:10.1039/c7cc09128a

A new class of electrophilic phosphonium cations (EPCs) containing a -CF₃ group attached to the phosphorus(v) center is readily accessible in high yields, via a scalable process. These species are stable to air, water, alcohol and strong Br?nsted acid, even at raised temperatures. Thus, P-CF₃ EPCs are more robust than previously reported EPCs containing P-X moieties (X = F, Cl, OR), and despite their reduced Lewis acidity they function as Lewis acid catalysts without requiring anhydrous reaction conditions.

Full text of DOI:10.1039/c7cc09128a

View Article Online
View Journal
ChemComm
Accepted Manuscript
This article can be cited before page numbers have been issued, to do this please use: V. Fasano, J.
LaFortune, J. Bayne, M. J. Ingleson and D. W. Stephan, Chem. Commun., 2017, DOI:
10.1039/C7CC09128A.
This is an Accepted Manuscript, which has been through the
Volume 52 Number
1 4 January 2016 Pages 1–216
Royal Society of Chemistry peer review process and has been
accepted for publication.
ChemComm
Accepted Manuscripts are published online shortly after
Chemical Communications
www.rsc.org/chemcomm
acceptance, before technical editing, formatting and proof reading.
Using this free service, authors can make their results available
to the community, in citable form, before we publish the edited
article. We will replace this Accepted Manuscript with the edited
and formatted Advance Article as soon as it is available.
You can find more information about Accepted Manuscripts in the
author guidelines.
Please note that technical editing may introduce minor changes
to the text and/or graphics, which may alter content. The journal’s
standard Terms & Conditions and the ethical guidelines, outlined
in our author and reviewer resource centre, still apply. In no
event shall the Royal Society of Chemistry be held responsible
for any errors or omissions in this Accepted Manuscript or any
consequences arising from the use of any information it contains.
ISSN 1359-7345
COMMUNICATION
Marilyn M. Olmstead, Alan L. Balch, Josep M. Poblet, Luis Echegoyenet al.
Reactivity differences of Sc3N@C2n (2n 68 and 80). Synthesis of the
first methanofullerene derivatives of Sc N@D5h-C80
=
3
rsc.li/chemcomm

Please do not adjust margins
ChemComm
Page 1 of 4
View Article Online
DOI: 10.1039/C7CC09128A
Journal Name
COMMUNICATION
Air- and water-stable Lewis acids: synthesis and reactivity of
P-trifluoromethyl electrophilic phosphonium cations
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
V. Fasano,[a,b] J. H. W. LaFortune,[b] J. M. Bayne,[b] M. J. Ingleson*[a] and D. W. Stephan*[b]
www.rsc.org/
A
new class of electrophilic phosphonium cations (EPCs)
containing a -CF3 group attached to the phosphorus (V) center is
readily accessible in high yields, via a scalable process. These
species are stable to air, water, alcohol and strong Brønsted acid,
even at raised temperatures. Thus, P-CF3 EPCs are more robust
than previously reported EPCs containing P-X moieties (X = F, Cl,
OR), and despite their reduced Lewis acidity they function as Lewis
acid catalysts without requiring anhydrous reaction conditions.
Since the first report on metal-free reversible dihydrogen
activation,1 frustrated Lewis pair (FLP) chemistry has gained
attention from the chemical community due to the potential
for applications in important transformations (e.g. reductions).
This strategy, exploiting the combined action of sterically
encumbered Lewis acids and Lewis bases has been used to
activate a variety of small molecules (e.g. H2, R3SiH, CO2).2
Scheme 1. Examples of EPCs and their relative stability.
The Lewis acidity of [(C6F5)3PF]+ is derived from the
energetically low-lying σ* orbital oriented opposite to the
polar P–F bond. While the fluorine atom and the C6F5 ring(s)
boost the Lewis acidity of EPCs, the presence of the P-F moiety
results in limited stability, particularly with respect to water
and alcohols. This limitation has prompted the search for more
Most typically,
the Lewis
acids employed
are
tri(fluoroaryl)boranes (and derivatives), although other
elements have been reported as the locus of the electrophilic
character (e.g. Al, Si, Ga, C),3 including phosphorus. While
Wittig reagents4 are perhaps the most notable example of P
(V) Lewis acids, in the past decade other examples of
phosphorus-based electrophiles have been reported.5 In 2013
the synthesis and the catalytic applications of a new class of P
(V) Lewis acids was reported.6 The first example of such
electrophilic phosphonium cations (EPCs) [(C6F5)3PF]+ (Scheme
1, A) was employed as a catalyst in a variety of transformations
robust EPCs. In FLP chemistry,
a number of different
approaches have been pursued to provide water and alcohol
compatibility, for example, the utility of Sn cations or less
Lewis acidic boranes have been explored.3b,
15
However, to
date air and water stable EPCs that are still active for σ-bond
activation remains an open problem. One approach that has
mimicked efforts to enhance the chemical robustness of
electrophilic boranes, has been the replacement of C6F5 with
C6Cl5 rings.16 While this increases the steric bulk around the
Lewis acidic phosphorus center, the P-F bond remains prone to
hydrolysis (Scheme 1, B).17 An alternative strategy has been
the replacement of fluoride with aryloxy groups. With
[(C6F5)3POPh]+ for example this achieved a modest increase in
stability to ROH, although these species degrade in CH2Cl2
solution on exposure to atmospheric moisture after 1.5 h
(Scheme 1, C).18 In a related effort, the 1,2-diphosphonium
dication [(C10H6)(Ph2P)2]2+ was shown to be stable for 24 h to
air in the solid state, although rapid hydrolysis occurred in
non-purified (wet) solvents (Scheme 1, D).19
including
hydrodefluorination,6
dehydrocoupling,7
compounds,8
hydrosilylation
of unsaturated
hydrodeoxygenation of ketones,9 amides,10 and phosphine-
oxides,11 FLP-hydrogenations,12 Friedel-Crafts arylations of
fluoro-alkanes13 and hydroarylation of alkynes.14
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 1
Please do not adjust margins

Please do not adjust margins
ChemComm
Page 2 of 4
View Article Online
DOI: 10.1039/C7CC09128A
COMMUNICATION
While the above data illustrate that enhanced water
Journal Name
tolerance of EPCs requires replacement of the P-halogen bond,
high electronegativity of the substituent is essential to produce
a low energy σ* orbital required for strong Lewis acidity. Thus
the synthesis of CF3 (electronegativity: 3.5)20 derived
phosphonium cations was targeted. Synthetic protocols to this
new class of EPCs are presented herein. Despite a modest
reduction in Lewis acidity, these species are shown to be
effective in a variety of Lewis acid catalysis while exhibiting a
significant increase in tolerance to ROH relative to other EPCs.
To the best of our knowledge, [Ph3PCF3]+, [1]+ is the only
known example of a P-CF3 EPC. Umemoto and co-workers21
synthesized this species in-situ via direct electrophilic
Figure 1. POV-ray depictions of the cations of (a) [1]+ and (b) [2]+; H atoms and anions
are omitted for clarity. C: black, P: orange, F: pink. (c) LUMO of [1]+, (d) LUMO of [2]+
(isovalues at 0.04).
trifluoromethylation of Ph3P using
a
highly reactive
trifluoromethylsulfonium cation. In our hands, all efforts to
prepare [1]+ (and related P-CF3 EPCs) by use of Umemoto’s or
Togni’s reagents,22 by radical trifluoromethylation or by
nucleophilic reactions of [R3P-X] with CF3-anions, failed.
Seeking an alternative strategy, installation of the CF3-group
prior to quaternization of the phosphine was undertaken.
Using the method of Caffyn and co-workers,23 Ph2PCF3 was
synthesized in high yield from Ph2POPh and Me3SiCF3 in the
presence of half an equivalent of CsF. Subsequent
quaternization of phosphorus was achieved via reaction with
MeOTf or a Pd(0)-catalyzed reaction with PhOTf yielding
[Ph2PCF3(Me)][OTf] ([2][OTf]) and [Ph3PCF3][OTf] ([1][OTf]) in
high yield, respectively (Scheme 2). Subsequent treatment of
[1][OTf] with [K][B(C6F5)4] afforded [1][BArF] via anion
metathesis.
These salts could be stored as solids under ambient
conditions for months with no observable degradation.
Moreover, even in non-purified solvents at temperatures up to
100oC, or in the presence of excess water, alcohol, phenol /
aniline combinations, or stoichiometric HCl, no degradation
1
was evident by H, 31P or 19F NMR spectroscopy. However, in
the presence of water and base (e.g. aniline), rapid formation
of Ph3PO and HCF3 resulted. Apart from this reactivity, the
resistance to strong Brønsted acids is notable as boranes
utilized in FLP chemistry either bind these Lewis bases or
degrade via protodeboronation under acidic conditions.24
DFT calculations at the M06-2X/6-311G(d,p) level with
DCM solvation (by polarizable continuum model) were used to
probe the Lewis acidity of these salts. The optimized structures
showed the lower torsion angles for the aryl rings in [2]+ (-
118°) in comparison to [1]+ (-126°) consistent with the
increased steric congestion in [1]+ prompting the increased
torsion angle and reduced conjugation of the phenyl rings with
the σ* orbital. The hydride ion affinity (HIA) of [1]+ and [2]+
(relative to BEt3) was computed at the same level of theory.
HIA values of -19.2 and -19.5 kcal mol-1 were obtained for [1]+
and [2]+, respectively. These values are notably larger than
that found for the catalytically active borane BPh3 (HIA = -10.5
kcal mol-1).25 The LUMO of each of these cations is mainly
comprised of the σ* orbital of the P-CF3 fragment, although
the LUMO of [2]+ has a greater contribution on the phenyl
rings in comparison to [1]+ due to the lower torsion angle in
the former (Figure 1(c), (d)).
Scheme 2. Synthesis of [1][OTf], [2][OTf] and [1][BArF].
To further probe the effect of conjugation between the
Single crystals of each of these salts, [1][OTf], [2][OTf]
σ
* orbital and aryl substituent(s), computations for the EPC in
and [2][BArF] were obtained and characterized by X-Ray
diffraction studies (Figure 1) confirming the formulation. This
revealed no significant contacts between the cations and
anions in each case. Replacement of the methyl group of [2]+
with a phenyl ring in [1]+ resulted in an increase of the steric
environment around the phosphorus centre, with [1]+
assuming a more propeller-like shape (lowest torsion angles –
which two of the phenyl rings are linked, [(C12H8)PPh(CF3)]+
[3]+ (Figure 2) were also performed. The reduced torsion angle
for the biphenyl fragment (-70°), led to more delocalization of
the LUMO onto the biphenyl fragment and reduced
contribution with the isolated phenyl ring where the torsion
angle increases to -147°. This also results in a reduced HIA on P
for [3]+ compared to [1]+ (-17.9 and -19.5 kcal mol-1,
respectively).
involving the F3C-P-C-CH- fragment – were -105° and -113° for
[2][OTf] and [1][OTf], respectively).
2 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Please do not adjust margins
ChemComm
Page 3 of 4
View Article Online
DOI: 10.1039/C7CC09128A
Journal Name
COMMUNICATION
BnOSi(H)Et2 in 90% yield. Treatment of benzaldehyde with 1.2
equivalents of PhMe2SiH in the presence of a catalytic amount
of either [1][OTf] or [1][BArF] at 60 °C led to good reduction of
the carbonyl affording Bn2O and (PhMe2Si)2O (Scheme 3, C).
Analogously, benzophenone or acetophenone were both
reduced at 100 °C with [1][BArF] as the catalyst in the
presence of 2.2 equivalents of PhMe2SiH leading to a mixture
of silyl-ether and the deoxygenated product alkane (Scheme 3,
C). In contrast, the catalyst [1][OTf] proved inactive under
these conditions, although reductive de-arylation of [1]+ did
generate Ph2PCF3 and PhOTf. The superior catalytic activity of
[1][BArF] is thus attributed to the more weakly nucleophilic
anion. Also in those cases, repeating the reactions under
ambient conditions in non-purified solvents resulted in good
reduction of the carbonyls despite the competitive
dehydrosilylation of water.3b, 26
Figure 2. LUMO orbital for [3] (isovalues at 0.04).
The computations of the Lewis acidity of [1]+ and [2]+
prompted experiments targeting their use as Lewis acid
catalysts. EPCs have been shown to effect catalytic
hydrodefluorination.6 Thus the EPC salts were evaluated in the
reaction of 1-fluoroadamantane with Et3SiH. While modest
hydrodefluorination was observed at 60 °C, using [1][OTf] or
[1][BArF] the conversions were improved at 100 °C with the
latter giving excellent reactivity after 18 h (Scheme 3, A). Most
notably, repeating the reaction under ambient conditions with
un-purified solvent / reactants resulted only in a small
diminishing of the conversion.
Treatment of N-benzylidene aniline with 1.2 equivalents
of PhMe2SiH in the presence of a catalytic amount of [1][BArF]
at 100 °C gave full imine reduction leading mainly to the
corresponding hydrosilylated product (Scheme 3, D) and
similar conversion again was observed when the reaction was
performed under ambient conditions. Under non-anhydrous
conditions, Brønsted acid catalysis has been observed. For
example, CF3CO2H has been shown to activate silanes.27
However, the low Lewis acidity of the P-CF3 EPCs towards H2O
disfavours this possibility and the reactivity observed is more
consistent with EPC activation of silane. This was supported by
H/D scrambling being observed using freshly distilled
Ph2MeSiH and Et3SiD in anhydrous DCM, under inert
atmosphere, in the presence of 5 mol % of [1][OTf]
.
Recently, EPCs were also shown to initiate the
Mukaiyama aldol addition reaction28 under strictly anhydrous,
but otherwise mild conditions. Indeed, use of 5 mol% of the
salts of [1]+ and [2]+ proved effective in initiating the aldol
reaction of 2-naphthaldehyde and 1-methoxy-2-methyl-1-
trimethylsiloxypropene in CDCl3, affording quantitative yields
of the addition product after 24 h at room temperature
(Scheme 4).
Scheme 3. Transformations catalysed by [1]. In brackets the conversion under ambient
conditions in unpurified solvent. For A, the conversions are based on 19F-NMR spectra
using fluorobenzene as standard. For B-D, the conversions are based on 1H-NMR using
mesitylene as standard. For aldehyde / ketone reductions, the product further reacted
losing siloxane, as previously reported.9
Scheme 4. Mukaiyama aldol reaction with [2][OTf], [1][OTf] and [1][BArF].
In summary, the first example of an air and water-stable
EPC catalyst has been reported.29 This new class of catalyst is
based on the inclusion of a more robust CF3 substituent as the
essential highly electronegative component of the EPC. This
class of catalyst has shown high tolerance to ROH, including
water, allowing them to be stored under ambient conditions
and to be used without rigorous exclusion of water from the
reaction mixture. Experimental and computational evidence
demonstrate that the P-CF3 cation decorated with three phenyl
rings is sufficiently Lewis acidic to be a useful Lewis acid
catalyst, with an inert anion helping to insure no
decomposition at high temperature. While this new class of
Similarly, investigation of the dehydrocoupling of silanes
and alcohols was probed (Scheme 3, B). Combination of phenol
and Et2SiH2, in the presence of 5 mol% [2][OTf] as catalyst
showed limited reactivity (19% conversion), whereas [1][OTf]
and [1][BArF] afforded PhOSi(H)Et2 in high yield. Once again,
repeating the reaction under ambient conditions with
unpurified solvent / alcohols had minor effect on the catalyst
performance. When BnOH was used as alcohol and Et2SiH2 as
silane in the presence of 5 mol% [2][OTf] as catalyst at 20 °C or
at elevated temperatures no reaction was observed. However,
using [1][OTf] or [1][BArF] as the catalyst, dehydro-coupling of
silane and benzyl-alcohol at 60 °C proceeded affording
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 3
Please do not adjust margins

Please do not adjust margins
ChemComm
Page 4 of 4
View Article Online
DOI: 10.1039/C7CC09128A
COMMUNICATION
Journal Name
14. J. H. W. LaFortune, J. M. Bayne, T. C. Johnstone, L. Fan and D. W.
Stephan, Chem. Commun., 2017, 53, DOI:
EPCs have a lower catalytic activity compared to that of
previous EPCs, [1]+ represents a balance between air- and
water-stability and catalytic activity. Furthermore, compound
[1][BArF] is readily accessible not requiring strong oxidants
(XeF2) or highly sensitive silylium cations [Et3Si][BArF] as
reported for the more reactive fluorophosphonium EPCs.[5] On
the basis of this work, the generation of other readily
accessible, water-stable EPCs is under investigation.
10.1039/C1037CC08037A.
15. (a) T. Mahdi and D. W. Stephan, J. Am. Chem. Soc., 2014, 136,
15809-15812; (b) D. J. Scott, M. J. Fuchter and A. E. Ashley, J.
Am. Chem. Soc., 2014, 136, 15813-15816; (c) Á. Gyömöre, M.
Bakos, T. Földes, I. Pápai, A. Domján and T. Soós, ACS Catalysis,
2015, DOI: 10.1021/acscatal.5b01299, 5366-5372; (d) D. J. Scott,
T. R. Simmons, E. J. Lawrence, G. G. Wildgoose, M. J. Fuchter
and A. E. Ashley, ACS Catalysis, 2015, 5, 5540-5544; (e) D. J.
Scott, N. A. Phillips, J. S. Sapsford, A. C. Deacy, M. J. Fuchter and
A. E. Ashley, Angew. Chem. Int. Ed., 2016, 55, 14738; (f) V.
Fasano, J. E. Radcliffe and M. J. Ingleson, ACS Catalysis, 2016, 6,
1793-1798; (g) E. Dorko, M. Szabo, B. Kotai, I. Papai, A. Domjan
and T. Soos, Angew. Chem. Int . Ed., 2017, 56, 9512-9516.
16. (a) A. E. Ashley, T. J. Herrington, G. G. Wildgoose, H. Zaher, A. L.
Thompson, N. H. Rees, T. Kramer and D. O'Hare, J. Am. Chem.
Soc., 2011, 133, 14727-14740; (b) H. Zaher, A. E. Ashley, M.
Irwin, A. L. Thompson, M. J. Gutmann, T. Kramer and D. O'Hare,
Chem. Commun., 2013, 49, 9755-9757.
We are grateful to the Royal Society of Chemistry for a
Research Mobility Grant (V.F.) and the University of
Manchester for financial support. D.W.S. acknowledges the
financial support of the NSERC of Canada and the award of a
Canada Research Chair. M.J.I. acknowledges the EPSRC (grant
numbers EP/K03099X/1 and EP/M023346/1) for financial
support. Dr. Alan Brisdon is thanked for useful discussions.
Additional research data supporting this publication are
available as supplementary information accompanying this
publication
17. S. Postle, V. Podgorny and D. W. Stephan, Dalton Trans., 2016,
45, 14651-14657.
18. J. H. W. LaFortune, T. C. Johnstone, M. Pérez, D. Winkelhaus, V.
Podgorny and D. W. Stephan, Dalton Trans., 2016, 45, 18156-
18162.
Conflicts of interest
The authors declare no conflict of interest.
19. M. H. Holthausen, J. M. Bayne, I. Mallov, R. Dobrovetsky and D.
W. Stephan, J. Am. Chem. Soc., 2015, 137, 7298-7301.
20. F. R. Leroux, B. Manteau, J.-P. Vors and S. Pazenok 4, Beilstein J.
Org. Chem., 2008, 4, doi:10.3762/bjoc.3764.3713.
Notes and references
21. T. Umemoto and S. Ishihara, J. Am. Chem. Soc., 1993, 115, 2156.
22. S. Barata-Vallejo, B. Lantano and A. Postigo, Chemistry, 2014,
20, 16806-16829.
1. G. C. Welch, R. R. S. Juan, J. D. Masuda and D. W. Stephan,
Science, 2006, 314, 1124-1126.
2. (a) D. W. Stephan, J. Am. Chem. Soc., 2015, 137, 10018-10032; (b)
D. W. Stephan, Acc. Chem. Res., 2015, 48, 306-316; (c) D.
Stephan and G. Erker, Isr. J. Chem., 2015, 55, 133-133; (d) D. W.
Stephan and G. Erker, Angew. Chem. Int. Ed., 2010, 49, 46-76.
3. (a) S. A. Weicker and D. W. Stephan, Bull. Chem. Soc. Jap., 2015,
88, 1003-1016; (b) V. Fasano, J. E. Radcliffe, L. D. Curless and M.
J. Ingleson, Chem. Eur. J., 2017, 23, 187.
4. G. Wittig and U. Schöllkopf, Chem. Ber., 1954, 87, 1318-1330.
5. D. W. Stephan, Angew. Chem. Int . Ed., 2017, 56, 5984 -5992.
6. C. B. Caputo, L. J. Hounjet, R. Dobrovetsky and D. W. Stephan,
Science, 2013, 341, 1374-1377.
23. M. B. Murphy-Jolly, L. C. Lewis and A. J. M. Caffyn, Chem.
Commun., 2005, 4479.
24. S. Das and S. K. Pati, Chem. Eur. J., 2017, 23, 1078.
25. (a) D. Mukherjee, DanielF.Sauer, A. Zanardi and J. Okuda, Chem.
Eur.J., 2016, 22, 7730 -7733; (b) D. Mukherjee, S. Shirase, K.
Mashima and J. Okuda, Angew. Chem. Int. Ed., 2916, 55, 13326.
26. V. Fasano and M. J. Ingleson, Chem. Eur. J., 2017, 23, 2217.
27. M. P. Doyle and C. T. J. West, J. Org. Chem., 1975, 40, 3835.
28. A. G. Barrado, J. M. Bayne, T. C. Johnstone, C. W. Lehmann, D.
W. Stephan and M. Alcarazo, Dalton Trans., 2017, DOI:
10.1039/c1037dt03197a.
7. M. Pérez, C. B. Caputo, R. Dobrovetsky and D. W. Stephan, Proc.
Nat. Acad. Sci., 2014, 111, 10917-10921.
29. Whilst the initial silane activation step requires the phosphorus
Lewis acid we acknowledge it is feasible that subsequent
catalytic cycles may be mediated by a silicon electrophile, for a
related example using a strong Brønsted acid see: Q.-A. Chen, H.
F. T. Klare, M. Oestreich, J. Am. Chem. Soc., 2016, 138, 7868.
8. M. Pérez, L. J. Hounjet, C. B. Caputo, R. Dobrovetsky and D. W.
Stephan, J. Am. Chem. Soc., 2013, 135, 18308-18310.
9. M. Mehta, M. H. Holthausen, I. Mallov, M. Pérez, Z. W. Qu, S.
Grimme and D. W. Stephan, Angew. Chem. Int . Ed., 2015, 54,
8250-8254.
10. A. Augurusa, M. Mehta, M. Pérez, J. T. Zhu and D. W. Stephan,
Chem. Commun., 2016, 52, 12195-12198.
11. M. Mehta, I. G. de la Arada, M. Pérez, D. Porwal, M. Oestreich
and D. W. Stephan, Organometallics, 2016, 35, 1030-1035.
12. T. vom Stein, M. Pérez, R. Dobrovetsky, D. Winkelhaus, C. B.
Caputo and D. W. Stephan, Angew. Chem. Int . Ed., 2015, 54,
10178-10182.
13. (a) J. T. Zhu, M. Pérez and D. W. Stephan, Angew. Chem. Int .
Ed., 2016, 55, 8448-8451; (b) J. Zhu, M. Pérez, C. B. Caputo and
D. W. Stephan, Angew. Chem. Int . Ed., 2016, 55, 1417-1421.
4 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins