Cyclic aromatic analogues of the hendrickson reagent; NMR studies and electrophilic properties

Article abstract of DOI:10.1055/s-0031-1289998

Two novel cyclic aromatic analogues of the Hendrickson POP reagent, 1,1,3,3-tetraphenyl-1,3-dihydro-2,1,3-benzoxadiphosphole-1,3-diium bis(trifluoromethanesulfinate) and bis(trifluoromethanesulfonate), have been readily prepared by the treatment of 1,2-bis(diphenylphosphino)benzene or 1,2-bis(diphenylphosphoryl)benzene, respectively, with trifluoromethanesulfonic anhydride in dichloromethane. ³¹P and ¹⁹F NMR studies indicated that while the latter complex is formed as the sole product, the former species was shown to be the predominant component in equilibrium with 1-(diphenylphosphino)-2-[diphenyl(trifluoromethylsulfonyloxy)phosphonio]benzene trifluoromethanesulfinate and 1,2-bis[diphenyl(trifluoromethylsulfonyloxy) phosphonio]benzene bis(trifluoromethanesulfinate). The dehydrating POP systems were exploited in the conversion of aldoximes into nitriles. The dehydration occurred rapidly at room temperature and produced high yields with a variety of alkyl- and arylaldoximes, tolerating a wide range of substrates and functional groups. Georg Thieme Verlag Stuttgart New York.

Full text of DOI:10.1055/s-0031-1289998

460
PAPER
Cyclic Aromatic Analogues of the Hendrickson Reagent; NMR Studies and
Electrophilic Properties
Cyclic
Analogu
i
es of th
a
e
H
endrick
d
sonReagent Moussa*
Department of Chemistry, Taibah University, P.O. Box 30002, Almadinah Almunawarrah, Saudi Arabia
E-mail: zmousa@taibahu.edu.sa
Received 10 November 2011; revised 30 November 2011
Dedicated to Professor Daniel Romo
tem has since been successfully used in a number of func-
Abstract: Two novel cyclic aromatic analogues of the Hendrickson
‘POP’ reagent, 1,1,3,3-tetraphenyl-1,3-dihydro-2,1,3-benzoxadi-
phosphole-1,3-diium bis(trifluoromethanesulfinate) and bis(tri-
fluoromethanesulfonate), have been readily prepared by the
treatment of 1,2-bis(diphenylphosphino)benzene or 1,2-bis(diphenyl-
phosphoryl)benzene, respectively, with trifluoromethanesulfonic
anhydride in dichloromethane. 31P and 19F NMR studies indicated
that while the latter complex is formed as the sole product, the
former species was shown to be the predominant component in
equilibrium with 1-(diphenylphosphino)-2-[diphenyl(trifluorometh-
ylsulfonyloxy)phosphonio]benzene trifluoromethanesulfinate and
1,2-bis[diphenyl(trifluoromethylsulfonyloxy)phosphonio]benzene
bis(trifluoromethanesulfinate). The dehydrating ‘POP’ systems
were exploited in the conversion of aldoximes into nitriles. The de-
hydration occurred rapidly at room temperature and produced high
yields with a variety of alkyl- and arylaldoximes, tolerating a wide
range of substrates and functional groups.
tional group interconversions,8–10 and in the syntheses of
several natural products11–19 and heterocyclic building
blocks for biologically active molecules.20–25
The aforementioned promising prospects associated with
the synthetic versatility of Hendrickson’s reagent provid-
ed the impetus for the Jenkins’ group to develop five-,
six-, and seven-membered cyclic bisphosphine analogues,
which proved successful in ester and amide synthesis,26
and were recently used to prepare 2-oxazolines, 2-thiazo-
lines, and 2-dihydrooxazine.27 These had the advantage of
liberating one mole of the phosphine oxide byproduct per
dehydration reaction.
In an attempt to find an alternative dehydrating agent, we
became interested in using triphenyl(trifluoromethyl-
Key words: 1,2-bis(diphenylphosphino)benzene, 1,2-bis(diphe- sulfonyloxy)phosphonium trifluoromethanesulfinate (2)
nylphosphoryl)benzene, trifluoromethanesulfonic anhydride,
(Scheme 2) as an alternative oxygen activator and dehy-
drating reagent.28 Surprisingly, we discovered that it
Hendrickson reagent, dehydration, aldoximes, nitriles
could be directly prepared from triphenylphosphine and
trifluoromethanesulfonic anhydride by mixing them in
In the past few years, the Hendrickson ‘POP’ reagent 1
(triphenylphosphonium anhydride trifluoromethane-
sulfonate),1 prepared instantly at 0 °C by reacting triphe-
nylphosphine oxide with trifluoromethanesulfonic
anhydride in a 2:1 stoichiometry, has demonstrated wide
applicability as an effective dehydrating agent and its
many proven applications have been well-documented
(Scheme 1).2 Hendrickson erroneously postulated that the
reagent was the monophosphonium salt, triphenyl(trifluo-
1.3:1 stoichiometric ratio, respectively. NMR studies in-
dicated that the reaction produces an equilibrium mixture
consisting mainly of 2 and the corresponding triphe-
nylphosphonium anhydride bis(trifluoromethanesulfi-
nate) (3). It is noted, though, that both reacted readily and
cleanly at 0 °C to effect instantaneous dehydration of al-
doximes into nitriles. The main advantages of this reagent
is that it avoids the formation of a double stoichiometric
amount of triphenylphosphine oxide and does not require
the extra unnecessary step of oxidizing the phosphine into
the corresponding oxide prior to trifluoromethylsulfona-
tion, as often done in the preparation of known phosphine-
based dehydrating agents.
romethylsulfonyloxy)phosphonium
trifluoromethane-
sulfonate [Ph3P(OTf)2] which was subsequently shown by
Aaberg et al. to be the diphosphonium analogue
[(Ph3P+)2O·2 OTf–].3 Dehydrations and coupling reactions
are induced through an alkoxyphosphonium salt, the same
common intermediate often observed in the Mitsunobu re-
action.4–7 It is noted, though, that the Hendrickson ‘POP’
reagent has several advantages over the Mitsunobu reac-
tion, where the recovered triphenylphosphine oxide may
be recycled by treatment with trifluoromethanesulfonic
anhydride, it obviates the need for explosive azodicarbox-
ylates, and the alkylation of the hydrazinedicarboxylate
and other side reactions are averted. The dehydrating sys-
In continuation of our previous work in this area, herein
we report the preparation of two aromatic cyclic bisphos-
phine analogues 5 and 7 of the Hendrickson ‘POP’ re-
agent (Scheme 3). The advantage of these analogues over
the Hendrickson reagent is that they liberate one mole of
the phosphine oxide byproduct per dehydration reaction.
With the latter reagent, the release of two moles of tri-
phenylphosphine oxide exacerbates the problem of sepa-
ration of the product by chromatography. On the other
hand, the bisphosphine oxide byproduct produced from
the cyclic analogues is considerably more polar than triph-
enylphosphine oxide because of the two phosphine oxide
moieties, thus rendering purification more facile. For in-
SYNTHESIS 2012, 44, 460–468
x
x
.x
x
.2
0
1
1
Advanced online publication: 22.12.2011
DOI: 10.1055/s-0031-1289998; Art ID: T105811SS
© Georg Thieme Verlag Stuttgart · New York

PAPER
Cyclic Analogues of the Hendrickson Reagent
461
a
Hendrickson's
"POP" reagent
2 Ph3P=O
+
Tf2O
(Ph3P+)2O•2OTf–
1
R-CN
O
O
O
R
S
N
R
NH2
R
Nu
or
O
N
H
R-C=NOH
NuH
O
O
+
S
R
O–
NR4
O
Hendrickson's
"POP" reagent
HN
R
R2
R1
N
H
R2
N
R3
R2
STr
OMe
H
O
O
PhCO2H, DIPEA
HOCH2CH2NH2
R1
N
H
O
R2
N
O
R2
R2
OMe
O
S
R1
N
R1
N
R3
Scheme 1 A selection of transformations promoted by the Hendrickson reagent 1. Reagents and conditions: (a) Ph3PO/Tf2O (2:l stoichiome-
try), 0 °C, CH2Cl2.
stance, the retention factor values in a solvent system of bis(diphenylphosphoryl)benzene (6) with trifluoro-
ethyl acetate–diethyl ether (1:1) for 1,2-bis(diphenylphos- methanesulfonic anhydride (Scheme 3). Proof of the
phoryl)benzene and triphenylphosphine oxide are 0.04 structure for 6 was secured via spectroscopic methods by
and 0.33, respectively.
the use of 1D/2D 1H, 13C, and 31P NMR, and IR techniques
(see Supporting Information).29–31
One further advantage is that these five-membered ring
analogues may produce significant improvement in the We initially determined the appropriate stoichiometry of
reaction rates of certain transformations as noted by 6 to trifluoromethanesulfonic anhydride required to pro-
Jenkins.26 For example, a marked increase in the rate of duce the electrophilic phosphonium anhydride salt 7 and
esterification was achieved with the five-membered ring whether any double trifluoromethylsulfonation of 6
analogue versus the six- and seven-membered ring homo- would occur. In principle, the bis-phosphine oxide 6 may
logues and the Hendrickson reagent. This was attributed react with up to two stoichiometric amounts of trifluo-
to the ease of formation of the putative phosphorane inter- romethanesulfonic anhydride to afford a mixture of 7 and
mediate. In contrast, the Hendrickson reagent resulted in
significantly greater rate constant than that for the six- and
O
O
+
+
O
seven-membered ring analogues presumably due to the
higher positive charge on the phosphorus atoms in the
former. Unlike Jenkins’ cyclic reagents where the phos-
phorus atoms are connected by electron-donating alkyl
tethers, 5 and 7 feature an aromatic linker which is antici-
pated to render them more electrophilic with relatively
higher positive charge on the phosphorus atoms.
Ph2P
PPh2
Ph2P
PPh2
Ph2P
PPh2
a
b
–
6
4
2 CF3SO2
5
c
OTf OTf
+
Ph2P
O +
PPh2
+
+
The cyclic phosphonium anhydride 7 was easily prepared
from commercial 1,2-bis(diphenylphosphino)benzene (4)
by oxidation with excess hydrogen peroxide and subse-
quent trifluoromethylsulfonation of the resulting 1,2-
Ph2P
PPh2
not observed
2 CF3SO2O–
2 CF3SO2O–
7
8
a
Ph3P + Tf2O
(Ph3P+)OTf•Tf– + (Ph3P+)2O•2Tf–
Scheme 3 Reagents and conditions: preparation of 5: (a) 4/Tf2O
(1:1 stoichiometry), r.t., 20 min, CH2Cl2; preparation of 7: (b) excess
H2O2 (30%), 30 min, r.t., CH2Cl2, 99%; (c) 6/Tf2O (1.3:1 stoichiome-
try), r.t., 10 min, CH2Cl2.
2
3
Scheme 2 Reagents and conditions: (a) Ph3P/Tf2O (1.3:1 stoichio-
metry), 0 °C, CH2Cl2.
© Thieme Stuttgart · New York
Synthesis 2012, 44, 460–468

462
Z. Moussa
PAPER
8. This is critical as trifluoromethanesulfonic anhydride it- tage of such a reagent is that it saves the extra unnecessary
self is an indiscriminate electrophile and any remaining step of oxidizing the phosphine into the corresponding ox-
unreacted excess will veil the true identity of the electro- ide prior to trifluoromethylsulfonation. In this case
philic species responsible for dehydration. Thus, a though, the reaction may produce two non-cyclic products
dichloromethane solution of 1,2-bis(diphenylphosphor- alongside 5, where one phosphorus atom or both are tri-
yl)benzene (6) (1.0 mmol) at 0 °C was first treated with fluoromethylsulfonated. Thus, a dichloromethane solu-
two molar equivalents of trifluoromethanesulfonic anhy- tion of 4 (1.0 mmol) at 0 °C was first treated with two
dride (2.0 mmol) and the reaction progress was monitored molar equivalents of trifluoromethanesulfonic anhydride
by analyzing aliquots by 19F, 31P, 1H, and 13C NMR spec- and reaction progress was monitored by analyzing ali-
troscopy (see Supporting Information). These techniques quots by 1H, 13C, 31P, and 19F NMR spectroscopy. The 19F
were complementary and proved decisive in tracking the NMR spectrum of an aliquot taken 10 minutes after the
disappearance of each reagent and the emergence of new addition of trifluoromethanesulfonic anhydride showed
species. The 19F NMR spectrum of an aliquot taken 10 three signals at d = –78.1 (s), –71.7 (s), and –31.4 ppm
minutes after the addition of trifluoromethanesulfonic an- (dd, J = 15.0, 4.1 Hz) integrating as 1.00:0.80:0.37, re-
hydride showed two signals at d = –71.7 (s), and –78.1 spectively. Clearly, copious amount of trifluoromethane-
ppm (s) integrating as 1.00:0.93, respectively. The singlet sulfonic anhydride remained unreacted. Interestingly, the
at d = –78.1 ppm was attributed to the trifluoromethane- 31P NMR spectrum of the same aliquot showed three sig-
sulfonate ion and that at d = –71.7 ppm was assigned to nals at d = 82.2 (s), 44.7 (dq, J = 29.4, 4.1 Hz), and –9.93
trifluoromethanesulfonic anhydride as verified indepen- ppm (overlapped dq, J = 29.4, 15.1 Hz) integrating as
dently by the 19F NMR signal (d = –71.7 ppm) of a com- 1.74:1.09:1.00, respectively (Figure 1, spectrum a).
mercial sample. The 13C NMR spectra provided further
support for the presence of the latter species which exhib-
its a distinctive quartet at d = 118.3 ppm (J = 320 Hz) that
matches the 13C NMR chemical shift and coupling con-
stant obtained from an authentic sample. The 31P NMR
spectrum showed one singlet at d = 49.6 ppm and the sig-
nal for 6 which usually occurs at d = 31.8 ppm was not de-
tected. The presence of one molar equivalent of unreacted
trifluoromethanesulfonic anhydride as suggested by the
1.00:0.93 ratio and the exclusive presence of one product
as indicated by the 31P NMR clearly suggest that the for-
mation of the cyclic anhydride 7 is favored over the alter-
native bis-trifluoromethylsulfonated non-cyclic analogue
8. Indeed, when 1,2-bis(diphenylphosphoryl)benzene (6)
(1.0 mmol) was treated with one molar equivalent of tri-
fluoromethanesulfonic anhydride (1.0 mmol) under the
same conditions outlined earlier, the same product 7
formed instantaneously and promptly precipitated as a
white solid within the first 10 minutes following mixing
of the two reagents. It is noteworthy that 1.3 mmol of 6
Figure 1 31P NMR stack spectra (162 MHz) for the addition of Tf2O
(2 equiv) to 4 in CH2Cl2. The signal at d = 49.7 ppm was truncated to
allow close stacking: (a) Tf2O (2 equiv), 0 °C, 10 min; (b) Tf2O (2
equiv), 0 °C to r.t., 1 h.
was required to completely consume the trifluo-
19
romethanesulfonic anhydride (1.0 mmol) within the pre-
ceding time period. The high sensitivity of the product to
moisture precluded isolation and made complete charac-
terization difficult. For instance, shortly after removing
the supernatant and exposing the solid residue to air, it
turned into 1,2-bis(diphenylphosphonous acid)benzene
(see Supporting Information), pointing to its highly hy-
groscopic property. However, evaporating the solvent un-
der an inert atmosphere and adding chloroform-d allowed
The singlets at d = –78.1 and –71.7 ppm in the F NMR
were assigned to the trifluoromethanesulfinate ion and
trifluoromethanesulfonic anhydride, respectively. The
doublet of doublets at d = –31.4 ppm in the 19F NMR and
the doublets of quartets at d = 44.7 and –9.93 ppm
in the 31P NMR were attributed to 1-(diphenylphosphino)-
2-[diphenyl(trifluoromethylsulfonyloxy)phosphonio]ben-
zene trifluoromethanesulfinate (9) which comprised 55%
of the mixture (Figure 2).
1
it to be characterized by H, 13C DEPT-90, 13C, COSY,
The peak multiplicity and similar coupling constants of
the doublet of doublet in the 19F NMR and doublets of
quartets in the 31P NMR (Figure 2) corroborate the pro-
posed structure of complex 9, where the 3JP-P vicinal cou-
pling value is 29.4 Hz and the long-range JP-F values are
15.0 and 4.1 Hz. Further evidence to support 9 stems from
the upfield chemical shift for the diphenylphosphino
group (–9.93 ppm) and its complex first-order multiplet
HSQC, 19F, and 31P NMR spectroscopy. Alternatively,
this species may be formed and characterized directly in
chloroform-d.
As in the preceding studies, the appropriate stoichiometry
of the reaction between 4 and trifluoromethanesulfonic
anhydride required to produce the electrophilic phospho-
nium anhydride salt 5 was investigated. The main advan-
Synthesis 2012, 44, 460–468
© Thieme Stuttgart · New York

PAPER
Cyclic Analogues of the Hendrickson Reagent
463
methylsulfonyloxy oxygen with concomitant release of
trifluoromethanesulfinate ion as the leaving group. Evi-
dence to support this stems from the diminished integra-
tion value for the signal of complex 10 at d = 82.2 ppm,
which suggest that its formation is reversible and that 9 is
continuously regenerated from 10 during the cyclization
process, noting that the latter species could not undergo
cyclization. Surprisingly, when the same reaction was
conducted at room temperature under the same condi-
tions, the desired cyclic anhydride 5 and 9 were the only
two products present (5/9; 1.0:0.96 integration), where the
former was the major product. These optimized condi-
tions were subsequently used in the upcoming dehydra-
tion reactions.
Next, the electrophilic properties of the cyclic analogues
5 and 7 and their effectiveness as oxygen activators were
evaluated. 2-Chlorobenzaldehyde oxime was used as a
model compound in a complexation/dehydration study
with 7 and progress of the reaction was monitored by 31P
and 19F NMR spectroscopy (Figure 3). The reagent 7 was
prepared under the optimal conditions reported earlier in
which slight excess of the bisphosphine oxide 6 was em-
ployed, as excess trifluoromethanesulfonic anhydride
could react with the oxime (Figure 3, spectrum a and b).
The oxime (1.0 equiv) underwent immediate complex-
ation at 0 °C with 7 to give a single complex as shown by
the 31P NMR spectrum (Figure 3, spectrum c). Finally, ad-
dition of excess triethylamine resulted in immediate and
clean dehydration of the oxime to the corresponding ni-
trile in high yield, with concomitant elimination of oxide
6 as demonstrated in Figure 3, spectrum d.
Figure 2 19F and 31P NMR spectral evidence for complex 9 and the
corresponding bis-trifluoromethylsulfonated analogue 10
where peak coincidence arises from a doublet of quartet
with coupling constants of 29.4 and 15.1 Hz. The remain-
ing far downfield singlet at d = 82.2 ppm in the 31P NMR
(Figure 1, spectrum a) was assigned to 1,2-bis[di-
phenyl(trifluoromethylsulfonyloxy)phosphonio]benzene
bis(trifluoromethanesulfinate) (10, comprising 45% of the
mixture) where the weak long-range JP-F was not ob-
served. Surprisingly, the phosphonium anhydride salt 5
was not detected at all. However, when the reaction was
warmed to room temperature over one hour, a fourth sig-
nal corresponding to 5 appeared in the 31P NMR at d =
49.7 ppm (s) in addition to the other three peaks observed
earlier (integrating as 1.0:1.14:1.08:0.17) (Figure 1, spec-
trum b).
Product 5, which promptly precipitated as a white solid,
was isolated by the removal of the supernatant following
several washes with cold dichloromethane. The clean
1
product was characterized in chloroform-d by H, 13C
DEPT-90, 13C, COSY, HSQC, 19F, and 31P NMR spec-
troscopy (see Supporting Information), where all spectra
were near identical to those obtained earlier for the phos-
phonium anhydride analogue 7. It appears that 5, which
comprises 32% of the mixture, is formed at the expense of
9 (63%) and 10 (5%) as evident from the integration val-
ues obtained for the mixture of the three species. Thus, the
significant decrease in the integration for the signal at d =
82.2 ppm from 1.74 to 0.17 and the simultaneous emer-
gence of the resonance at d = 49.7 ppm, coupled with a
slight increase in integration values for the signals stem-
ming from complex 9 (Figure 1, spectra a, b) clearly sup-
port this proposition. A possible mechanism for the
formation of complex 5 would involve an intramolecular
Figure 3 19F and 31P NMR reaction profile for the conversion of 2-
chlorobenzaldehyde oxime into 2-chlorobenzonitrile; (a) 19F NMR
after mixing 6 with Tf2O (1.3:1), CH2Cl2, r.t., 5 min; (b) 31P NMR af-
ter mixing 6 with Tf2O (1.3:1), CH2Cl2, r.t., 5 min; (c) 2-chloro-
cyclization of precursor 9 by attack of the phosphorus benzaldehyde oxime (1 equiv) was added to the reaction mixture at
r.t.; (d) the reaction mixture was treated with Et3N (2.6 equiv).
atom of the diphenylphosphino group on the trifluoro-
© Thieme Stuttgart · New York
Synthesis 2012, 44, 460–468

464
Z. Moussa
PAPER
As with 7, the reagent system comprising 5 (1.0 mmol) tion of 7, it is less likely to be formed from the correspond-
was prepared under the optimal conditions reported earli- ing analogue 5 and more likely to be formed from an
er and treated with the oxime (1 equiv) under the same intramolecular fluorination of the phosphine atom of com-
conditions as above. The two main species present in the plex 9 (Scheme 4). It is noted that 13 does not form in all
reagent system 5 and 9 underwent immediate complex- instances and its generation may be associated with cer-
ation to give the expected complexes as observed in tain deviations or subtle changes in temperature and time
Figure 4 (spectrum a) at d = 49.4 (s), 44.6 (dq, J = 29.2, of mixing reagents. Although the mechanistic aspects are
3.2 Hz), and –10.2 ppm (dq, J = 11.0, 29.2 Hz).
interesting, this side product bears no significance to the
thrust of this work and thus was not pursued further.
O
Cl
Ph2P
PPh2
H
path a
N
path a
O
P
12
Ph
Ph
OSO2CF3
PPh2
Ph2F2P
PPh2
path b
path b
–
CF3SO2
11
13
Scheme 4 Plausible pathways for the conversion of intermediate 11
into 12 and 13
Figure 4 19F and 31P NMR reaction profile for the conversion of 2-
chlorobenzaldehyde oxime into 2-chlorobenzonitrile; (a) 2-chloro-
benzaldehyde oxime (1 equiv) was added to the reagent system pre-
pared from 4 (0.5 mmol), Tf2O (0.5 mmol), CH2Cl2, r.t., 20 min; (b)
the reaction mixture was treated with Et3N (2 equiv); (c) an expanded
region of the 19F NMR following addition of Et3N.
With a preliminary proof of concept for the dehydrating
abilities of 5 and 7 in hand, the versatility of the preceding
protocol was examined on various structurally diverse al-
doximes 14 derived from aromatic (entries 1, 2, and 4–
12), heterocyclic (entries 13–15), and aliphatic (entry 3)
substrates (Table 1). Using the optimized conditions as
shown in Table 1 where the reagents were used in excess
to ensure complete conversion, the dehydration proceeded
rapidly at room temperature and produced high yields of
the corresponding nitriles 15.32 Whereas the 31P NMR of
all crude reactions showed 6 to be the sole side product in
the dehydration reactions of 7 and the major one in those
involving 5, a new minor and as yet unidentified species
appeared at dP = 28.6 ppm (s) in addition to those observed
earlier in Figure 4. The reagents tolerated a wide range of
substrates and functional groups such as methoxy, trifluo-
romethoxy, halogens, and nitro. Moreover, the dehydrat-
ing systems exhibited some degree of chemoselectivity
(entries 13, 14, and 16) as the oxime function reacted pref-
erentially over the phenolic hydroxy group and pyridine
nitrogen. In the latter case, the nitrogen atom may ring
open 5 or 7, and can be envisioned to undergo trifluoro-
methylsulfonation by 9 to afford the corresponding pyri-
dinium trifluoromethanesulfonate with concomitant
formation of 12. Interestingly, ring-activating and -deacti-
vating substituents had no significant effect on the rate of
reaction or yields as all nitriles shown in Table 1 were
produced almost immediately following addition of tri-
Whereas the major complex at d = 49.4 ppm (integrating
for 1.0) was derived from 5, the one with chemical shifts
at d = 44.6 and –10.2 ppm (integrating for 0.95 overall)
was formed from the reaction of the oxime with 9. It is
noted that the signal for the double-substitution product
was not observed in part due to the relatively lower con-
centration of the precursor species 10 and its reversible
formation. Finally, the addition of excess triethylamine
resulted in immediate dehydration of the oxime to the cor-
responding nitrile. The 31P NMR spectrum (Figure 4,
spectrum b) shows a signal for the expected 1,2-bis(diphe-
nylphosphoryl)benzene [6, d = 31.8 ppm (s)] as the major
elimination product and two signals for 1-(diphenylphos-
phino)-2-(diphenylphosphoryl)benzene (12) at d = 30.8
(d, J = 15.7 Hz) and –14.1 ppm (d, J = 15.7 Hz). The NMR
spectral data of the latter known compound, an eliminated
product of complex 11 that was isolated by column chro-
matograph, matched those reported.31 Lastly, an unex-
pected product with chemical shifts in the 31P spectrum at
d = –11.1 (td, J = 33.2, 21.5 Hz) and –48.5 ppm (td, J =
666, 21.5 Hz), and d = –32.7 ppm (dd, J = 666, 33.7 Hz)
in the 19F spectrum (Figure 4, spectrum c) has been attrib-
uted to 1-[difluorodiphenylphosphoranyl)-2-(diphe-
nylphosphino)benzene (13) (Scheme 4). Since such a
product was not observed earlier in the dehydration reac-
1
ethylamine. All products were characterized by H and
13C NMR spectroscopy and compared with authentic
commercial samples.
Synthesis 2012, 44, 460–468
© Thieme Stuttgart · New York

PAPER
Cyclic Analogues of the Hendrickson Reagent
465
Table 1 Dehydration of Aldoximes into Nitrilesa,b
H
method A or B
N
R
CN
15
R
OH
14
Entry
1
Substratec
Product
Yieldd (%)
Method A
Method B
85
81
OH
PhCN
Ph
Ph
Ph
N
2
91
96
95
OH
CN
N
3e
93
OH
OH
CN
N
N
CN
4
5
6
88
95
92
90
98
94
OMe
OMe
OH
CN
N
F3CO
F3CO
CN
Cl
OH
N
N
Cl
OH
CN
7
8
85
86
87
89
Cl
Cl
Cl
Cl
OH
CN
Cl
N
Cl
F
F
OH
N
CN
Cl
9
95
96
N
Cl
OH
CN
Cl
10
11
91
92
94
94
Cl
OH
Cl
Cl
CN
N
NO2
NO2
OH
CN
N
12
13
89
91
91
93
O2N
O2N
CN
CN
N
N
OH
N
OH
N
14
15
93
82
95
85
N
O
N
O
CN
OH
N
© Thieme Stuttgart · New York
Synthesis 2012, 44, 460–468

466
Z. Moussa
PAPER
Table 1 Dehydration of Aldoximes into Nitrilesa,b (continued)
H
method A or B
N
R
CN
15
R
OH
14
Entry
16
Substratec
Product
Yieldd (%)
Method A
Method B
79
Br
OH
Br
CN
N
77
HO
Br
HO
Br
a Method A via 5: 14 (0.25 mmol), 4 (0.5 mmol), Tf2O (0.5 mmol), Et3N (1–1.3 mmol), CH2Cl2, r.t., 40 min; Method B via 7: 14 (0.25 mmol),
6 (0.65 mmol), Tf2O (0.5 mmol), Et3N (1–1.3 mmol), CH2Cl2, r.t., 40 min.
b Products were characterized by 1H and 13C NMR spectroscopy and compared with authentic commercial samples.
c 0.5 equiv was used to ensure complete conversion.
d Isolated unoptimized yields.
e The substrate consisted of a mixture of E/Z isomers (1:0.6).
below; spectra for 5, 6, 7, 12, and 1,2-bis(diphenylphosphonous
acid) are given in the Supporting Information.
In summary, we have prepared and characterized two cy-
clic aromatic analogues of the Hendrickson ‘POP’ re-
agent, 5 and 7. They were prepared by the treatment of
1,2-bis(diphenylphosphino)benzene and 1,2-bis(diphe-
nylphosphoryl)benzene with trifluoromethanesulfonic an-
hydride in dichloromethane, respectively. 31P and 19F
NMR studies indicated that while the latter complex
formed as the sole product, the former species has been
established as the predominant component in equilibrium
with 1-(diphenylphosphino)-2-[diphenyl(trifluoromethyl-
sulfonyloxy)phosphonio]benzene trifluoromethanesulfi-
nate (9) and traces of 1,2-bis[diphenyl(trifluoro-
1,1,3,3-Tetraphenyl-1,3-dihydro-2,1,3-benzoxadiphosphole-
1,3-diium Bis(trifluoromethanesulfinate) (5)
Freshly distilled Tf2O (84.0 mL, 0.5 mmol) was added slowly to a
soln of 1,2-bis(diphenylphosphino)benzene (4, 223 mg, 0.5 mmol)
in anhyd CH2Cl2 (4.5 mL) at r.t. under an N2 atmosphere. A floccu-
lent white precipitate formed after ca. 30 min and the mixture was
left to stir for 6 h total. When the precipitate had settled, the light-
yellow supernatant was removed under an inert atmosphere and the
white residue was washed several times with cold CH2Cl2 and re-
dissolved in CDCl3 (suspension) and analyzed by NMR.
1H NMR (400 MHz, CDCl3): d = 7.93–7.87 (m, 2 H), 7.68–7.59 (m,
4 H), 7.57–7.39 (m, 18 H).
methylsulfonyloxy)phosphonio]benzene
bis(trifluoro-
methanesulfinate) (10). The electrophilic properties of the
preceding dehydrating systems have been utilized in the
development of a mild method for converting aldoximes
into nitriles, rapidly at room temperature in high yields.
The method tolerates a wide range of substrates and func-
tional groups and has been shown to exhibit some degree
of chemoselectivity. Hence, this method should find utili-
ty in synthesis and may prove to be a valuable alternative
to known methods. The new ‘POP’ reagents are currently
being investigated in other dehydration and coupling reac-
tions in order to determine their general applicability and
the results will be reported in due course.
13C NMR (100 MHz, CD3CN–CDCl3): d = 136.5 (t, J = 11.7 Hz, 2
CH), 133.9 (br s, 4 CH), 133.1 (dt, J = 10.3, 10.3 Hz, 2 CH), 131.5
(dt, J = 11.0, 9.5 Hz, 8 CH), 130.8 (dd, J = 98.2, 7.0 Hz, 2 C), 128.7
(dt, J = 13.2, 8.9 Hz, 8 CH), 123.2 (dd, J = 112.9, 1.5 Hz, 4 C), 119.5
(q, J = 320 Hz, 2 CF3).
31P (162 MHz, CDCl3): d = 49.7 (s).
19F (376.5 MHz, CDCl3): d = –78.1 (s).
1,2-Bis(diphenylphosphoryl)benzene (6)
A CH2Cl2 soln (150 mL) of 1,2-bis(diphenylphosphino)benzene (4,
3.33 g, 7.46 mmol) was treated with excess 30 wt% aq H2O2 (29
mL) and the mixture stirred at r.t. for 30 min (1H NMR monitoring
indicated complete conversion). The CH2Cl2 layer was washed with
H2O (2 × 100 mL), dried (anhyd NaSO4), and concentrated. Recrys-
tallization of the residue (CH2Cl2–Et2O) afforded 1,2-bis(diphe-
nylphosphoryl)benzene (3.53 g, 99%) as a white solid; mp 189–190
°C (Lit.30b 146–147 °C, it is noted that a similar mp was initially ob-
tained in the presence of remaining CH2Cl2, however upon drying
the sample overnight, a higher mp was obtained).
IR (KBr): 1202 (P=O), 1117 cm–1 (P=O).
1H NMR (400 MHz, CDCl3): d = 8.03–7.93 (m, 2 H), 7.70–7.63 (m,
2 H), 7.51–7.42 (m, 8 H), 7.41–7.36 (m, 4 H), 7.31–7.24 (m, 8 H).
13C NMR (100 MHz, CDCl3): d = 135.6 (dd, J = 98.2, 8.5 Hz, 2 C),
135.4 (t, J = 10.6 Hz, 2 CH), 132.7 (d, J = 107.9 Hz, 4 C), 131.5 (dt,
J = 10.0, 3.0 Hz, 8 CH), 130.9 (br s, 4 CH), 130.7 (dt, J = 8.0, 6.0
Hz, 2 CH), 127.4 (dt, J = 13.0, 6.0 Hz, 8 CH).
Unless otherwise noted, all materials were used as received from a
commercial supplier without further purification. All reactions were
monitored by analytical TLC plates and analyzed with 254 nm UV
light. Known compounds were characterized by 1H and 13C NMR,
IR, and melting points (where applicable) and compared to their lit-
erature values. IR spectra were recorded (KBr) on a Perkin Elmer
1650 spectrophotometer. 1H (400 MHz) and 13C NMR (100 MHz)
spectra were recorded on Avance II Bruker FT NMR spectrometer
400 using CDCl3 or CD3CN as solvents relative to TMS as an inter-
nal reference. The yields refer to the isolated yields of compounds
1
estimated to be 95% pure as determined by H NMR. Melting
points were obtained on a Fisher-Johns melting point apparatus and
are uncorrected. NMR spectral data of 5, 6, 7, 12 are summarized
31P (162 MHz, CDCl3): d = 31.8 (s).
Synthesis 2012, 44, 460–468
© Thieme Stuttgart · New York

PAPER
Cyclic Analogues of the Hendrickson Reagent
467
1,1,3,3-Tetraphenyl-1,3-dihydro-2,1,3-benzoxadiphosphole-
1,3-diium Bis(trifluoromethanesulfonate) (7)
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.
Freshly distilled Tf2O (168 mL, 1.0 mmol) was added slowly to a
soln of 1,2-bis(diphenylphosphoryl)benzene (6, 622 mg, 1.30
mmol) in anhyd CH2Cl2 (10 mL) at r.t. under a N2 atmosphere. A
thick white precipitate was formed after ca. 10 min of mixing the re-
agents and the mixture was stirred for 30 min total. The solvent was
removed under an inert atmosphere and the residue was re-dis-
solved in CDCl3 and analyzed by NMR.
Acknowledgment
The author would like to thank Lena Moussa for the helpful discus-
sions and the Deanship of Scientific Research of Taibah University
for financial support (project number: 162).
1H NMR (400 MHz, CDCl3): d = 7.95–7.89 (m, 2 H), 7.66–7.59 (m,
4 H), 7.57–7.42 (m, 18 H).
References
13C NMR (100 MHz, CDCl3): d = 137.4 (t, J = 11.7 Hz, 2 CH),
134.8 (br s, 4 CH), 134.5 (dt, J = 10.0, 10.0 Hz, 2 CH), 132.4 (dt,
J = 11.0, 9.0 Hz, 8 CH), 131.4 (dd, J = 97.7, 7.0 Hz, 2 C), 129.7 (dt,
J = 14.0, 8.0 Hz, 8 CH), 124.0 (dd, J = 112.9, 1.5 Hz, 4 C), 120.2
(q, J = 320 Hz, 2 CF3).
31P (162 MHz, CDCl3): d = 49.6 (s).
19F (376.5 MHz, CDCl3): d = –78.1 (s).
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7.50 (m, 2 H), 7.47 (m, 1 H), 7.41 (m, 6 H), 7.36 (m, 1 H), 7.25 (m,
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138.9 (dd, J = 103.0, 32.2 Hz, C), 137.2 (dd, J = 11.0, 2.2 Hz, CH),
137.1 (d, J = 13.1 Hz, C), 134.2 (dd, J = 9.0, 12.2 Hz, CH), 133.5
(d, J = 104.6 Hz, C), 133.3 (d, J = 19.1 Hz, CH),132.2 (dd, J = 9.6,
2.3 Hz, CH), 131.8 (d, J = 2.6 Hz, CH), 131.4 (d, J = 2.8 Hz, CH),
128.6 (d, J =12.2 Hz, CH), 128.2 (d, J = 8.2 Hz, CH), 128.2 (br s,
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A CH2Cl2 soln (4.5 mL) of 1,2-bis(diphenylphosphino)benzene (4;
223 mg, 0.5 mmol) was treated with Tf2O (84.5 mL, 0.5 mmol) at r.t.
and the mixture was stirred for 20 min. The aldoxime 14 (0.25
mmol) was added as a CH2Cl2 soln (0.5–1.0 mL) and the mixture
was stirred for a further 5 min, followed by the addition of Et3N
(140 mL, 1.0 mmol). After stirring for a further 15 min, the mixture
was diluted with CH2Cl2 (10 mL) and washed with H2O (20 mL)
and brine (20 mL). The organic layer was dried (Na2SO4), and the
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Nitriles 15; General Procedure for Method B Using 6 and Tf2O
A CH2Cl2 soln (8.0 mL) of 1,2-bis(diphenylphosphoryl)benzene (6,
311 mg, 0.65 mmol) was treated with Tf2O (84.5 mL, 0.5 mmol) at
r.t. and the mixture stirred for 20 min. The aldoxime 14 (0.25 mmol)
was added as a CH2Cl2 soln (0.5–1.0 mL) and the mixture was
stirred for a further 5 min, followed by the addition of Et3N (180 mL,
1.3 mmol). After stirring for a further 15 min, the mixture was di-
luted with CH2Cl2 (10 mL) and washed with H2O (20 mL) and brine
(20 mL). The organic layer was dried (Na2SO4), and the residue was
purified (silica gel, 5% EtOAc–hexanes) to afford the nitriles 15
(Table 1).
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© Thieme Stuttgart · New York
Synthesis 2012, 44, 460–468

468
Z. Moussa
PAPER
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detailed preparation protocols and spectral data:
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Synthesis 2012, 44, 460–468
© Thieme Stuttgart · New York