Access to Stable Quaternary Phosphiranium Salts by P-Alkylation and P-Arylation of Phosphiranes

Article abstract of DOI:10.1055/s-0040-1708000

We report the preparation of phosphiranium salts by quaternarization of phosphiranes, a class of sensitive, highly strained, and poorly nucleophilic cyclic phosphines. High-yielding introduction of a varied set of alkyl groups including methylene ester ar

Full text of DOI:10.1055/s-0040-1708000

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© Georg Thieme Verlag Stuttgart · New York
2020, 31, A–F
letter
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J. Gasnot et al.
Letter
Synlett
Access to Stable Quaternary Phosphiranium Salts by P-Alkylation
and P-Arylation of Phosphiranes
Julien Gasnota
Ar1
Ar2
Ar1
P
Ar1
Ar1
Alk
CO2R
Clément Botellaa
Sébastien Comessea
Sami Lakhdarb
Carole Alayracb
Annie-Claude Gaumontb
Vincent Dalla*a
P-Alkylation
P
P
P
X
X
X
R
or P-Arylation
R
R
R
R
R
R
R
X = OTf, BF4, PF6
R = H, Me
15 examples
Yields up to 98%
Mild conditions
High efficiency
New groups
Catherine Taillier*a
a Normandie Univ., URCOM, UNIHAVRE, FR 3032, EA 3221,
25 Rue Philippe Lebon, BP 540, 76058 Le Havre, France
vincent.dalla@univ-lehavre.fr
catherine.taillier@univ-lehavre.fr
b Normandie Univ., LCMT, ENSICAEN, UNICAEN, CNRS,
6 Boulevard Marechal Juin, 14000 Caen, France
Received: 22.12.2019
Accepted after revision: 02.03.2020
Published online: 12.03.2020
that phosphiranes were generally appreciated as highly
strained species, moderately stable thermodynamically
and, in many instances, subject to ring fragmentations or
rearrangements.3
DOI: 10.1055/s-0040-1708000; Art ID: st-2020-b0683-l
Abstract We report the preparation of phosphiranium salts by quater-
narization of phosphiranes, a class of sensitive, highly strained, and
poorly nucleophilic cyclic phosphines. High-yielding introduction of a
varied set of alkyl groups including methylene ester arms was accom-
plished under mild conditions. A Cu-catalyzed electrophilic arylation of
phosphiranes using diaryl iodonium reagents was also achieved to yield
unprecedented P,P-diaryl phosphiranium salts with good efficiency.
General approach for phosphine quaternarization
Tertiary phosphines
R
Phosphiranes
Ar1
R
Ar1
R1
R
R
P
R1
P
P
P
R1
X
R1
X
X
R
R
X
R
R
R
R
Nucleophilic P
Ring strain
Poor Nu
Low stability
QPrS
QPS
Wide set of R1-X
(X = Cl, Br, I, OSO2R, ...)
Key words alkylation, arylation, phosphirane, phosphiranium salt,
alkylating agent, diaryliodonium salt
Few examples R1 = Me
R
1 = Alk
R1 = CH2-EWG
R1 = Ar2
This work
Nowadays, quaternary phosphonium salts (QPS) repre-
sent an important class of organophosphorus compounds
which have found a broad spectrum of applications ranging
from catalysis, organic synthesis to biological and medical
applications.1 It is therefore not surprising that the access
to a large panel of QPS has been widely documented. Until
recently, most of the QPS syntheses exploited the nucleo-
philic properties of phosphorus nonbonded lone pair of
electrons to form new bonds with a variety of electrophilic
species.2 In particular, the direct introduction of alkyl
groups on tertiary phosphines using alkyl halides (Cl, Br, I)
or related sulfonates (Ms, Ts, Tf) as electrophilic partners
has been extensively exploited over the years.
Compared to regular phosphines, the reactivity of phos-
phiranes, which are rather uncommon subtypes of cyclic
phosphines, was only scarcely studied (Scheme 1). These
three-membered phosphorus heterocyclic systems have
been viewed for long as elusive species being largely ne-
glected by the synthetic community. One main reason is
Scheme 1 General statement for tertiary phosphines (left) and phos-
phiranes (right) quaternarization
Moreover, theoretical calculations also revealed that
strain of the small P-heterocycles would cause partial delo-
calization of the phosphorus lone pair over the cycle, result-
ing in a decrease of nucleophilicity in comparison to tertia-
ry phosphines.4 In light of these structural characteristics
and the resultant reactivity uncertainties, the chemistry of
phosphiranes, and in particular quaternarization has been
barely approached. To our knowledge, only a handful of
such quaternarizations has been reported, all of which be-
ing performed using the highly electrophilic alkylating
agent methyl trifluoromethanesulfonate.5 Hence, the as-
sessment that phosphiranes can undergo quaternarization
with reliability and wide scope is still awaited. We have re-
cently endeavored to tackle this problem and now report
our preliminary results showcasing that phosphiranes are a
© 2020. Thieme. All rights reserved. Synlett 2020, 31, A–F
Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany

B
J. Gasnot et al.
Letter
Synlett
promising platform for easy synthesis of quaternary phos-
phiranium salts (QPrS) by alkylative and arylative function-
alization. In particular, an assortment of new derivatives,
including P-alkyl, P-methylene ester, and P-aryl units, with
appealing and untapped potential reactivity in organic syn-
thesis has been prepared.
Since we observed at the early stage of this study that
introduction of large substituents on phosphorus signifi-
cantly mitigated instability issues, we first selected as a
model substrate phosphirane 1a incorporating a mesityl
(Mes = 2,4,6-trimethylphenyl) substituent on P, for impar-
ting the ideal balance of thermal stability/resistance to air
oxidation/reactivity. Phosphirane 1a was prepared from its
parent primary phosphine MesPH2 using a straightforward
one-step reaction procedure.6
A preliminary study first focused on the screening of
classical methylating agents and reaction conditions for P-
methylation of 1a.7 Of the set of reagents tested, only the
highly electrophilic methyl trifluoromethanesulfonate
(MeOTf) appeared sufficiently reactive to enable alkylation
and form the desired phosphiranium salt 2a in almost
quantitative isolated yield (conditions A, Scheme 2).8 This
stands in full agreement both with literature precedents
and the expected weak nucleophilicity of 1a resulting from
the sterics and the ring strain/electronics relationship dis-
cussed above.
Like any strained three-membered ring systems, phos-
phiranium triflate 2a is characterized by extreme high field
1H, 13C, and 31P chemical shifts as well as large 1JC–P coupling
constants.9,10 It should also be noticed that, in the absence
of air and water, the phosphiranium 2a appeared complete-
ly stable over several months when stored at –20 °C. Modu-
lation of aryl substituents on phosphorus was next evalua-
ted. Preparation of the corresponding P-methyl-P-superme-
sityl phosphiranium 2b and its P-phenyl analogue 2c was
again performed using MeOTf (1 equiv) at room tempera-
ture in dichloromethane. Both reactions were rapid and
clean, requiring only 2 h of stirring at room temperature to
reach completion and give the desired compounds in high
yields (conditions A, 95% and 80%, respectively, from phos-
phiranes 1b and 1c). The high-yielding synthesis of phos-
phiranium 1c adorned with a simple phenyl deserves par-
ticular mention, given the relatively modest shielding em-
bedding this substituent.
R3
Ar
Ar
P
P
Conditions A–C
CH2Cl2, rt
X
R2
R1
R1
R2
1a–e
2a–f (R = Me)
3a–c (R = Allyl, Bn, Et)
Ph Me
P
Mes Me
P
Mes*
Me
P
OTf
OTf
OTf
1 h, Cond. A
2a 98%
1 h, Cond. A
2bb 95%
1 h, Cond. A
2c 80%
Mes Me
P
Mes Me
P
Mes Me
P
OTf
OTf
Me
BF4
Me
Me
1 h, Cond. A
2d 98% (dr = 77/23)c
1 h, Cond. A
2 h, Cond. B
2f 96%
2e n.d.d
Mes
Et
Mes
Ph
OTf
Mes
P
P
P
OTf
OTf
4 h, Cond. C
3a 95%e
4 h, Cond. C
3b 90%e
16 h, Cond. C
3c n.d.f
Scheme 2 Preparation of P-alkyl phosphiranium salts 2 and 3. Condi-
tions A: MeOTf (1–2 equiv), CH2Cl2. Conditions B: Me3O·BF4 (1 equiv),
CH2Cl2. Conditions C: ROTfa (1–1.2 equiv), CH2Cl2. a ROTf formed in situ
by reaction of Tf2O (1.2 equiv) and the corresponding alcohols (allylOH
or BnOH, 1.2 equiv) in the presence of DIPEA (1.2 equiv) in CH2Cl2 at
–30 °C (see Supporting Information for full details). b Mes* = 2,4,6-(t-
Bu)3Ph. c Reaction performed from the diastereoisomeric mixture of
syn- and anti-1-mesityl-2-methylphosphirane. For clarity, only the ma-
jor anti diastereoisomer of 2d was represented. d Reaction performed
from the racemic trans-1-mesityl-2,3-dimethylphosphirane (1e).
e Crude yield estimated (2 steps, from ROH). f Reaction run at 50 °C in
DCE; n.d. = not determined.
anti/syn = 77:23).12 As observed in the parent phosphirane
series, the C-substituted phosphiranium salt 2d appeared
to be much less stable than its unsubstituted analogue 2a,
and partial degradation occurred after only a few hours at
room temperature. These instability issues increased even
further with additional substitution as shown by the signif-
icant proportion of degradation products formed when at-
tempting to isolate the disubstituted phosphiranium salt 2e
from the reaction mixture.13
To verify whether the nature of the counteranion could
also be modified, P-methylation of 1a was next tested using
the Meerwein reagent (Me)3O+BF4 . The latter was found
–
equally effective as methyl triflate to form the correspond-
ing phosphiranium tetrafluoroborate salt 2f in high yield
within 2 h (96%, conditions B).8
The quaternarization of C-substituted phosphiranes was
next considered. Phosphiranes 1d and 1e, respectively, in-
corporating one or two methyl groups on the ring were
then reacted with methyl trifluoromethanesulfonate (con-
ditions A). Fast reactions were again observed leading to full
conversion of both phosphiranes 1d and 1e within 1 h to
form the corresponding salts 2d and 2e.11 On one hand, the
monosubstituted phosphiranium 2d could be isolated in
Rewardingly, it was also shown that the quaternariza-
tion step could expand beyond methylation. Indeed, we
were pleased to succeed in the P-allylation and P-benzyla-
tion of the phosphirane 1a to afford the phosphiranium tri-
flates 3a and 3b, which were isolated in good yields when a
sequential one-pot triflation/alkylation protocol was ap-
plied from allyl and benzyl alcohols, respectively (condi-
tions C).14,15
98% yield as
a
mixture of diastereoisomers (dr
© 2020. Thieme. All rights reserved. Synlett 2020, 31, A–F

C
J. Gasnot et al.
Letter
Synlett
Formation of the P-ethyl phosphiranium salt 3c was
also attempted from phosphirane 1a using the commercial-
ly available ethyl triflate.16 In this case, a prolonged reaction
time of 16 h and heating at 50 °C (conditions C) were found
critical to reach completion and, although the desired QPrS
3c could be formed as the major product, extensive decompo-
sition was also observed preventing its isolation in pure form.17
To broaden diversity and open new perspectives for fur-
ther functionalization, introduction of methylene ester
(–CH2CO2R) groups on phosphirane 1a was next considered.
Since we expected an increased electrophilicity of the –CH2
group adjacent to the proximal ester with respect to the
methyl, allyl, and benzyl halides, we first tested the use of
the commercially available bromo- and iodoacetate deriva-
tives. Apart from avoiding the tedious glycolic esters de-
rived triflate route while providing a simplified protocol,
these experiments were also intended to bring valuable in-
formation refining our knowledge of phosphiranes general
reactivity.
In line with earlier observations in methyl, allyl, and
benzyl series, a lack of reactivity was, unfortunately, ob-
served with only partial conversion of 1a and degradation
observed after prolonged reaction times. So, we finally had
to resort to synthesizing the corresponding triflate reagents
from the parent hydroxy esters. The triflation step was,
somehow surprisingly, a clean process which enabled easy
and high yielding (70–82%) isolation of the desired triflates
4a–d. Their reaction with 1a all proceeded smoothly to give
the expected methylene ester phosphiranium triflates 5a–d
in high yields (80–95%) irrespective of the ester group
(Scheme 3).18,19
ing the weak nucleophilicity of phosphiranes while demon-
strating the dominant influence of sterics on reactivity. Dis-
appointingly and for some unclear reasons, attempts to
switch the ester function by a trifluoromethyl group com-
pletely suppressed the alkylation, and no trace of the corre-
sponding quaternary phosphiranium salt 5e could be de-
tected when mixing 1a with the trifluoroethyl triflate 4e.
To further expand our phosphiranium salts portfolio, we
next focused on the introduction of aryl groups on phosphi-
rane 1a. We postulated that hypervalent iodine derivatives
should be suitable reagents for diarylphosphiranium salt
synthesis through electrophilic arylation of phosphirane
substrates,20,21 thus opening new perspectives in phosphi-
rane functionalization. We were delighted to be able to
demonstrate that this was indeed the case.
Table 1 shows selected results of our preliminary explo-
ration of a Cu/CuCl-catalyzed arylative quaternarization re-
action of 1a with diaryliodonium triflates 6a–c.20d,22 Reac-
tion of 1a with 6a was initially conducted in 1,1,2,2-tetra-
chloroethane at 140 °C. Under these relatively drastic
reaction conditions the diaryl phosphiranium salt 7a was
isolated in only 12% yield from the reaction mixture, in
spite of complete conversion (entry 1). To limit decomposi-
tion, we next performed a series of reactions at lower tem-
peratures and observed progressive yields enhancement
following gradual decrease of the temperature (48% at 80 °C
vs 81% at 50 °C, entries 2 and 3). A complete absence of re-
activity was, however, observed at room temperature (en-
try 4). It is worth mentioning that P,P-diarylphosphiranium
salt 7a proved less stable than its P-Me,P-aryl analogue 2a,
with faster decomposition occurring in solution even at
room temperature. The P,P-diarylphosphiranium salt 7a
was, however, found stable enough to be isolated by flash
column chromatography on silica gel and could be stored
neat for weeks at –20 °C, in the absence of air and water.
Preparation of the hexafluorophosphate salt analogue 7b
was run under the same conditions using diphenyliodoni-
um salt 6b. In stark contrast with the triflate case, tempera-
ture influenced the reaction outcome only marginally (54%
isolated yield at 80 °C vs 58% at 50 °C, entries 2 and 3 re-
spectively), thereby suggesting a greater instability of P,P-
diaryl QPrs paired with a hexafluorophosphate anion.
Last, introduction of the electron-rich and bulky p-tert-
butylphenyl group on 1a was attempted. Although the
starting phosphirane 1a was rapidly consumed either at
80 °C or 50 °C, the phosphiranium hexafluorophosphate
salt 7c was isolated in only 14% and 27% yields, respectively
(entries 2 and 3). At this stage, it is not clear whether these
low yields reflect an exacerbated instability of QPrS 7c un-
der the reaction conditions or are the results of an unfavor-
able aryl transfer.
TfO
EWG
Mes
EWG
OTf
Mes
P
4a–e
(1–1.2 equiv)
P
CH3CN, rt, 24 h
1a
5a–e
O
O
O
Mes
Mes
Mes
P
P
OiPr
P
OMe
OEt
OTf
OTf
OTf
5c 90%
5a 80%
Mes
5b >95%
O
Mes
CF3
OTf
P
P
OBn
OTf
5d 86%
5e 0%
Scheme 3 Preparation of P-methylene ester phosphiranium triflates
5a–e. Crude yields are given.
In all cases, slow reaction rates were observed, and the
reactions required an extended reaction time of 24 h (vs 2 h
for methylation) at room temperature to reach completion.
Heating and solvent change were also tested without any
improvement. As a whole, triflyloxy acetates 4a–d turned
out to be much more reactive than the corresponding ha-
lides, but clearly less than methyl triflate, thereby confirm-
In conclusion, we have described the preparation of un-
precedented quaternary phosphiranium salts, an intriguing
and barely explored class of quaternary phosphonium salts.
To this end, the singular reactivity of their phosphirane pre-
© 2020. Thieme. All rights reserved. Synlett 2020, 31, A–F

D
J. Gasnot et al.
Letter
Synlett
Table 1 Arylation of Phosphirane 1a with Diaryliodonium Reagents:
Optimization of Reaction Conditions
Ramsden, C. A., Ed.; Thieme: Stuttgart, 2007, 2083–2104. (c) For
the first example of QPS synthesis utilizing phosphine oxides as
electrophilic partners and Grignard reagents as nucleophiles,
see: Vetter, A. C.; Nikitin, K.; Gilheany, D. G. Chem. Commun.
2018, 54, 5843.
t-Bu
I(Ar)2X 6a–c
(1.2 equiv)
CuCl (10 mol%)
Cu cat.
(3) (a) Mathey, F. Chem. Rev. 1990, 90, 997. (b) Quin, L. D. In A Guide
to Organophosphorus Chemistry; Quin, L. D., Ed.; John Wiley &
Sons: New York, 2000, 234. (c) Mathey, F.; Regitz, M. In Phos-
Mes
P
Mes
Mes
Mes
P
P
P
PF6
PF6
OTf
TCE, 1 h
phorus-Carbon Heterocyclic Chemistry: The Rise of
a New
7a
7b
7c
1a
Domain; Mathey, F., Ed.; Elsevier Science: Amsterdam, 2001, 17.
(4) Henderson, W. A.; Buckler, S. A. J. Am. Chem. Soc. 1960, 82, 5794.
(5) (a) Hockless, D. C. R.; McDonald, M. A.; Pabel, M.; Wild, S. B.
J. Chem. Soc., Chem. Commun. 1995, 257. (b) Hockless, D. C. R.;
McDonald, M. A.; Pabel, M.; Wild, S. B. J. Organomet. Chem. 1997,
529, 189. For another recent example of isolated QPrS, see:
(c) Ficks, A.; Martinez-Botella, I.; Stewart, B.; Harrington, R. W.;
Clegg, W.; Higham, L. J. Chem. Commun. 2011, 47, 8274.
(6) For the synthesis of phosphirane substrates, see: (a) Mézailles,
N.; Fanwick, P. E.; Kubiak, C. P. Organometallics 1997, 16, 1526.
(b) Yang, F.; Fanwick, P. E.; Kubiak, C. P. Organometallics 1999,
18, 4222.
(7) Partial conversions of phosphirane 1a to the corresponding P-
methyl phosphiranium salts were observed after prolonged
reaction times using other methylating agents by 31P NMR mon-
itoring. Attempts to complete the methylation reactions all
failed to give the products in satisfactory yields. Prolonged reac-
tion times and heating were rather found to favor degradation
of both substrate 1a and quaternarization products. Results not
shown.
Entry
Temp (°C)
Yielda of 7a
(%)
Yielda of 7b
(%)
Yielda of 7c
(%)
1
2
3
4
140
80
12
48
81
NR
–
–
54
58
NR
14
27
NR
50
20
a Isolated yields are given; NR = no reaction.
cursors, which are highly strained and poorly nucleophilic
cyclic phosphines, was studied with regard to quaternariza-
tion. Introduction of a varied set of alkyl substituents, rang-
ing from methyl to methylene ester groups, could be ac-
complished in high yields when using the triflate reagents
as the alkylating agents. For triflates which are not com-
mercially available and highly sensitive, a straightforward
and efficient one-pot triflation/alkylation procedure was
developed. We have also demonstrated that use of hyperva-
lent iodine reagents in a Cu-catalyzed electrophilic aryla-
tion of phosphirane substrates could offer a facile access to
bisarylated compounds, thus broadening our library of
phosphiranium salts. This work allowed access to known
and new structures with fascinating yet untapped synthetic
potential for new phosphorus chemistry. Studies on those
aspects are currently ongoing in our laboratory and will be
reported in due course.
(8) General Procedure for the Preparation of P-Me Phosphira-
nium Salts 2 (Conditions A or B)
To a solution of phosphirane 1 (1.0 equiv) in CH2Cl2 (0.5 M) was
added methyl trifluoromethanesulfonate or trimethyloxonium
tetrafluoroborate (1.0–2.0 equiv) dropwise at room tempera-
ture. The mixture was then stirred at room temperature and
conversion of the starting material was monitored by 31P NMR
(approx. 2 h). The reaction mixture was then concentrated
under reduced pressure to give the title compounds 2.
1-Mesityl-1-methylphosphiran-1-ium Trifluoromethanesul-
fonate (2a)
Prepared from 1-mesitylphosphirane (1a, 0.84 mmol) using the
general procedure with methyl trifluoromethanesulfonate (2.0
equiv). Reaction time: 2 h. The title compound 2a was isolated
as a white solid (290 mg, 99% yield). Rf = 0.40 (CH2Cl2/EtOAc =
60:40); mp 58–60 °C. IR (neat):  = 2941, 1604, 1250, 1031, 940
cm–1. 1H NMR (300 MHz, CDCl3, 20 °C):  = 6.99 (d, 4JH–P = 6.0 Hz,
Funding Information
We gratefully acknowledge the region Haute-Normandie, the réseau
CRUNCH for grants to J.G. and C.B.; J.G. also thanks the University Le
Havre Normandie for financial support.()
4
2 H), 2.74–2.60 (m, 2 H), 2.57 (d, JH–P = 1.6 Hz, 6 H), 2.26 (s, 3
H), 2.20 (d, 2JH–P = 17.8 Hz, 3 H), 2.15–2.03 (m, 2 H). 13C NMR (75
MHz, CDCl3, 20 °C):  = 146.9 (d, 4JC–P = 3.0 Hz, Cq), 144.5 (d, 3JC–
2
1
Supporting Information
P = 11.0 Hz, 2 CH), 130.0 (d, JC–P = 13.2 Hz, 2 Cq), 120.3 (q, JC–
F = 320.2 Hz, Cq), 110.7 (d, 1JC–P = 93.8 Hz, Cq), 22.0 (d, 3JC–P = 9.1
Supporting information for this article is available online at
https://doi.org/10.1055/s-0040-1708000.
5
1
Hz, 2 CH3), 21.3 (d, JC–P = 1.7 Hz, CH3), 9.3 (d, JC–P = 4.4 Hz, 2
S
u
p
p
orit
n
gInformati
o
n
S
u
p
p
orti
n
gInformati
o
n
CH2P), 5.4 (d, JC–P = 50.1 Hz, CH3P). 31P NMR (121 MHz, CDCl3,
1
20 °C):  = –116.1. 19F NMR (282 MHz, CDCl3, 20 °C):  = –78.4.
HRMS (ESI): m/z calcd for C12H18P [M]+: 193.1146; found:
193.1144.
References and Notes
(9) The 31P NMR spectrum shows a single peak at –116.4 ppm for
2a, while the methyl group on P appears as a doublet at 2.20
ppm (2JP–H = 17.8 Hz) in the 1H NMR spectrum. In comparison,
the acyclic phosphonium analogue of 2a gives a signal at +21.2
ppm in the 31P NMR spectrum, see: Sattler, A.; Parkin, G. Chem.
Commun. 2011, 47, 12828.
(1) Berchel, M.; Jaffrès, P.-A. In Organophosphorus Chemistry: From
Molecules to Applications, 1st ed; Iaroshenko, V., Ed.; Wiley-
VCH: Weinheim, 2019, 59–111; and references cited therein.
(2) (a) Virieux, D.; Volle, J.-N.; Pirat, J.-L. In Science of Synthesis, Vol.
42; Mathey, F.; Trost, B. M., Ed.; Thieme: Stuttgart, 2009, 503–
594. (b) Tebby, J. C.; Allen, D. W. In Science of Synthesis, Vol. 31;
© 2020. Thieme. All rights reserved. Synlett 2020, 31, A–F

E
J. Gasnot et al.
Letter
Synlett
(10) Similarly, phosphiranes give the most upfield 31P NMR signals
known for tertiary phosphines. As a representative example,
our model phosphirane 1a gives a signal at –240.4 ppm in the
31P NMR spectrum.
20 °C):  = –114.1. 19F NMR (282 MHz, CDCl3, 20 °C):  = –78.5.
HRMS (ESI): m/z calcd for
C14H20
P
[M]+: 219.1303;
found: 219.1298.
(16) Crude yield estimated from 1H NMR analysis of the crude mix-
ture.
(11) (a) The stereochemistry anti and syn refers to the relative posi-
tion of the substituent on the ring carbon to the mesityl substit-
uent at phosphorus. The reaction was performed from a diaste-
reosiomeric mixture of syn- and anti-1-mesityl-2-
methylphosphirane (1d). (b) The reaction was performed from
the racemic trans-1-mesityl-2,3-dimethylphosphirane (1e).
(12) (a) Stereochemistry of the products 2d and 2e are proposed by
analogy and in accordance with Gaspar and co-workers’ work
who described the stereoselective synthesis of the parent phos-
phiranes 1d and 1e, see: Li, X.; Robinson, K. D.; Gaspar, P. P.
J. Org. Chem. 1996, 61, 7702. (b) It is worth noting that due to
instability issues, which differ from one diastereomer to
another in both the phosphirane and the phosphiranium series,
significant variations in the dr values of the isolated products
may be observed.
(13) It should be noted that due to their increased instability:
(a) HRMS and IR data are missing from the characterization of
phosphiranium 2d. (b) neither determination of a reliable
chemical yield nor full characterization of the quaternarization
product 2e could be done.
(14) Isolation of both allyl and benzyl triflate could not be realized.
Therefore, in situ formation of the triflate reagents and direct
addition of the reaction mixture onto a dichloromethane solu-
tion of phosphirane 1a at –30 °C was realized. For a similar pro-
cedure involving formation and direct use of allyl triflate, see:
Corey, E. J.; Helal, C. J. Tetrahedron Lett. 1996, 37, 5675.
(15) General Procedure for the Preparation of P-Alkyl Phosphira-
nium Triflate 3 (Conditions C)
(17) Formation of P-ethyl phosphiranium triflate 3c as a major
product was observed by monitoring progress of the quater-
narization reaction starting from phosphirane 1a by 1H NMR
and 31P NMR spectroscopy. The 31P NMR spectrum shows a
single peak at  = –109.6 ppm for 3c, while the ethyl group on P
appears as a dt at  = 1.42 ppm (3 H, 3JP–H = 27.0 Hz and 3JH–H = 7.6 Hz)
and a multiplet at  = 2.50–2.25 ppm (2 H) in the 1H NMR
spectrum.
(18) General procedure for the preparation of P-methylene ester
phosphiranium triflates 5:
a) Triflate Reagents Formation: To a solution of the corre-
sponding glycolic ester (1 equiv) and pyridine (1.3 equiv) in
CH2Cl2 (0.25 M) at –10 °C, was added triflic anhydride (1.15
equiv) dropwise, under argon atmosphere. Reaction was stirred
1 h at –10 °C and 3.5 h at room temperature. Degassed water
(0.2 M) was next added to the reaction mixture. After decanta-
tion, the aqueous layer was extracted with CH2Cl2 (3 × 5
mL/mmol). The combined organic layers were then combined,
dried over MgSO4, filtered, and concentrated under vacuum to
give the corresponding triflate reagents 4.
b) Alkylation of Phosphirane 1: To a solution of phosphirane
(1 equiv) in MeCN (0.2 M) was added the corresponding triflate
reagent 4 (1 equiv). The reaction mixture was then stirred at
room temperature under argon atmosphere until complete con-
version of phosphirane 1 (31P NMR monitoring, approx. 24 h).
The solvent was then removed under vacuum to give the crude
methylene ester phosphiranium salts 5.
To a solution of diisopropylethylamine (1.2 equiv) and the cor-
responding alkyl alcohol (1.2 equiv) in dry CH2Cl2 (0.6 M) at
–30 °C was added dropwise trifluoromethanesulfonic anhy-
dride (1.2 equiv) under argon atmosphere. The reaction mixture
was successively stirred 10 min at –30 °C, warmed to 0 °C, and
stirred for 10 min. The reaction mixture was again cooled to
–30 °C. Then, dry Et2O was added to precipitate the ammonium
salts. After decantation, the supernatant solution was added
dropwise to a solution of phosphirane 1 (1 equiv) in dry CH2Cl2
(1 M) at –50 °C. The reaction mixture was then allowed to warm
to room temperature over a period of 4 h, and stirring was
pursued at room temperature. Conversion of the starting mate-
rial was monitored by 31P NMR spectroscopy. Evaporation of the
solvent under reduced pressure then afforded the title product 3.
1-Allyl-1-mesitylphosphiranium Trifluoromethanesulfon-
ate (3a)
1-Mesityl-1-(2-ethoxy-2-oxoethyl)phosphiran-1-ium Triflu-
oromethanesulfonate (5b)
Prepared from 1-mesitylphosphirane (1a, 0.40 mmol) using the
general procedure with the triflate reagent derived from ethyl
glycolate (1.0 equiv). Reaction time: 24 h. The title compound
5b was isolated as a thick colorless oil (394 mg, 95% crude yield).
Rf = 0.23 (CH2Cl2/acetone = 50:50). IR (neat):  = 2985, 1724,
1606, 1243, 1223, 1156, 1027 cm–1
.
1H NMR (300 MHz, CDCl3,
4
3
20 °C):  = 7.09 (d, JP–H = 6.2 Hz, 2 H), 4.19 (q, JH–H = 7.2 Hz, 2
H), 4.03 (d, 2JP–H = 16.8 Hz, 2 H), 3.17–3.07 (m, 2 H), 2.71 (s, 6 H),
2.37 (s, 3 H), 2.28–2.18 (m, 2 H), 1.24 (t, 3JH–H = 7.2 Hz, 3 H). 13
C
2
NMR (75 MHz, CDCl3, 20 °C):  = 164.6 (d, JP–C = 5.1 Hz, C=O),
147.7 (d, 4JP–C = 3.2 Hz, Cq), 145.7 (d, 3JP–C = 11.4 Hz, 2 CH), 130.5
(d, 2JP–C = 14.0 Hz, 2 Cq), 120.4 (q, 1JF–C = 319.4 Hz, CF3), 109.1 (d,
1JP–C = 93.0 Hz, Cq), 63.5 (CH2), 30.0 (d, JP–C = 56.2 Hz, CH2P),
1
3
5
22.4 (d, JP–C = 8.5 Hz, 2 CH3), 21.7 (d, JP–C = 1.6 Hz, CH3), 13.8
(CH3), 10.3 (d, 1JP–C = 2.7 Hz, 2 CH2P). 31P NMR (121 MHz, CDCl3,
20 °C):  = –118.6. 19F NMR (282 MHz, CDCl3, 20 °C):  = –78.5.
HRMS (ESI): m/z calcd for C15H22O2P [M]+: 265.1357; found:
265.1360.
Prepared from 1-mesitylphosphirane (1a, 0.84 mmol) using the
general procedure with allyl alcohol (1.2 equiv). Reaction time:
4 h. The title compound 3a was isolated as a thick colorless oil
(350 mg, 95% crude yield). Rf = 0.15 (EtOAc). IR (neat):  = 2944,
1605, 1250, 1153, 1025, 940 cm–1
.
1H NMR (300 MHz, CDCl3,
(19) Crude yields are given since purification attempts only led to
the decomposition of the products.
4
20 °C):  = 7.03 (d, JH–P = 5.7 Hz, 2 H), 5.70 (m, 1 H), 5.55–5.39
2
3
(m, 2 H), 3.41 (dd, JH–P = 18.7 Hz and JH–H = 7.6 Hz, 2 H), 2.78–
2.68 (m, 2 H), 2.58 (br s, 6 H), 2.31 (s, 3 H), 2.20–2.10 (m, 2 H).
13C NMR (75 MHz, CDCl3, 20 °C):  = 147.3 (d, 4JC–P = 3.2 Hz, Cq),
(20) For examples of metal-catalyzed arylation of tertiary phos-
phines, see: (a) Ziegler, C. B. Jr.; Heck, R. F. J. Org. Chem. 1978, 43,
2941. (b) Marcoux, D.; Charette, A. B. J. Org. Chem. 2008, 73, 590.
(c) Marcoux, D.; Charette, A. B. Adv. Synth. Catal. 2008, 350,
2967. (d) Hanamoto T., Kiguchi Y., Shindo K., Matsuoka M.,
Kondo M.; Chem. Commun.; 1999, 151. For a photoredox reac-
tion mediated by a Ru-based photosensitizer, see: (e) Fearnley,
A. F.; An, J.; Lindovska, P.; Denton, R. M. Chem. Commun. 2016,
52, 4987.
3
2
145.2 (d, JC–P = 10.8 Hz, 2 CH), 130.2 (d, JC–P = 13.3 Hz, 2 Cq),
3
2
125.3 (d, JC–P = 16.2 Hz, CH2), 123.5 (d, JC–P = 14.0 Hz, CH),
120.3 (q, 1JC–F = 319.6 Hz, CF3), 109.3 (d, 1JC–P = 86.1 Hz, Cq), 25.8
1
3
(d, JC–P = 42.6 Hz, CH2P), 22.5 (d, JC–P = 7.9 Hz, 2 CH3), 21.5 (d,
5JC–P = 1.2 Hz, CH3), 9.0 (m, 2 CH2P). 31P NMR (121 MHz, CDCl3,
© 2020. Thieme. All rights reserved. Synlett 2020, 31, A–F

F
J. Gasnot et al.
Letter
Synlett
(21) For examples of metal-free arylation methods, see: (a) Wittig,
G.; Matzura, H. Angew. Chem., Int. Ed. Engl. 1964, 3, 231.
(b) Rémond, E.; Tessier, A.; Leroux, F. R.; Bayardon, J.; Jugé, S.
Org. Lett. 2010, 12, 1568. (c) Huang, W.; Zhong, C.-H. ACS Omega
2019, 4, 6690. (d) Bugaenko, D. I.; Volkov, A. A.; Livantsov, M. V.;
Yurovskaya, M. A.; Karchava, A. V. Chem. Eur. J. 2019, 25, 12502.
(22) General Procedure for the Preparation of Diaryl Phosphira-
nium Salts 6
Prepared from 1-mesitylphosphirane (1a, 0.14 mmol) using the
general procedure with diphenyliodonium triflate (1.2 equiv).
Reaction time: 1 h. The title compound 7a was isolated as a col-
orless oil (42 mg, 81% crude yield). Rf = 0.40 (CH2Cl2/acetone =
60:40). IR (neat): 1603, 1257, 1169, 1034, 636 cm–1 1H NMR
.
(300 MHz, acetone-d6, 20 °C):  = 7.93–7.82 (m, 2 H), 7.81–7.68
4
(m, 3 H), 7.35 (d, JH–P = 5.9 Hz, 2 H), 3.36–3.23 (m, 2 H), 3.08–
4
2.96 (m, 2 H), 2.70 (d, d, JH–P = 1.7 Hz, 6 H), 2.44 (s, 3 H). 13C
4
To a solution of phosphirane 1 (1 equiv) in 1,1,2,2-tetrachlo-
roethane (0.1 M) were added diphenyliodonium salt (1.2 equiv),
copper chloride (10 mol%), and copper metal wire (cat.) at room
temperature. The reaction mixture was then heated at 50 °C.
After cooling down to room temperature, the resulting crude
mixture was directly purified by flash column chromatography
on silica gel (eluent: CH2Cl2 then CH2Cl2/acetone, 60:40) to yield
the title product 7.
NMR (75 MHz, acetone-d6, 20 °C):  = 148.5 (d, JC–P = 3.1 Hz,
2
4
Cq), 147.1 (d, JC–P = 10.7 Hz, 2 Cq), 135.8 (d, JC–P = 4.5 Hz, CH),
3
3
133.4 (d, JC–P = 13.3 Hz, 2 CH), 131.6 (d, JC–P = 16.4 Hz, 2 CH),
131.1 (d, JC–P = 13.4 Hz, 2 CH), 122.3 (q, JC–F = 321.8 Hz, CF3),
2
1
1
1
115.2 (d, JC–P = 90.5 Hz, Cq), 109.2 (d, JC–P = 97.4 Hz, Cq), 22.6
(d, 3JC–P = 8.9 Hz, 2 CH3), 21.6 (d, 5JC–P = 1.4 Hz, CH3), 12.9 (d, 1JC–
P = 3.2 Hz, 2 CH2P). 31P NMR (121 MHz, acetone-d6, 20 °C):  = –
113.8. 19F NMR (282 MHz, acetone-d6, 20 °C):  = –78.9. HRMS
(ESI): m/z calcd for C17H20P [M]+: 255.1302; found: 255.1303.
1-Mesityl-1-phenylphosphiranium
fonate (7a)
Trifluoromethanesul-
© 2020. Thieme. All rights reserved. Synlett 2020, 31, A–F