NMR Studies and electrophilic properties of triphenylphosphine-trifluoromethanesulfonic anhydride; a remarkable dehydrating reagent system for the conversion of aldoximes into nitriles

Article abstract of DOI:10.1016/j.tetlet.2010.01.119

NMR Studies on the reaction of triphenylphosphine with various amounts of triflic anhydride at 0 °C is described. The reagent structure resulting from mixing 1.3 equiv of Ph₃P with Tf₂O (1.0 mmol) has been established as an equilibrium mixture consisting mainly of triphenyl(trifluoromethylsulfonyloxy)phosphonium trifluoromethanesulfinate and the corresponding bis(triphenyl)oxodiphosphonium trifluoromethanesulfinate dimer. The electrophilic properties of the system have been exploited in the development of a mild method for converting aldoximes into nitriles. The dehydration occurs at 0 °C under very mild conditions by initial activation of the oxime oxygen, followed by treatment with a base and subsequent elimination of triphenylphosphine oxide. The substrate scope and functional group tolerance of this useful method are explored.

Full text of DOI:10.1016/j.tetlet.2010.01.119

Tetrahedron Letters 51 (2010) 1826–1831
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
NMR Studies and electrophilic properties of
triphenylphosphine–trifluoromethanesulfonic anhydride; a remarkable
dehydrating reagent system for the conversion of aldoximes into nitriles
*
Ziad Moussa , Saleh A. Ahmed, Ahmad S. ElDouhaibi, Shaya Y. Al-Raqa
Department of Chemistry, Faculty of Science, Taibah University, PO Box 30002, Almadinah Almunawarrah, Saudi Arabia
a r t i c l e i n f o
a b s t r a c t
Article history:
NMR Studies on the reaction of triphenylphosphine with various amounts of triflic anhydride at 0 °C is
described. The reagent structure resulting from mixing 1.3 equiv of Ph3P with Tf2O (1.0 mmol) has been
established as an equilibrium mixture consisting mainly of triphenyl(trifluoromethylsulfonyloxy)phos-
phonium trifluoromethanesulfinate and the corresponding bis(triphenyl)oxodiphosphonium trifluorom-
ethanesulfinate dimer. The electrophilic properties of the system have been exploited in the development
of a mild method for converting aldoximes into nitriles. The dehydration occurs at 0 °C under very mild
conditions by initial activation of the oxime oxygen, followed by treatment with a base and subsequent
elimination of triphenylphosphine oxide. The substrate scope and functional group tolerance of this use-
ful method are explored.
Received 12 December 2009
Revised 15 January 2010
Accepted 29 January 2010
Available online 4 February 2010
Dedicated to Professor Thomas G. Back
Keywords:
Aldoximes
Nitriles
Ó 2010 Elsevier Ltd. All rights reserved.
Dehydration
Triphenylphosphine
Triflic anhydride
Triphenyl(trifluoromethylsulfonyloxy)-
phosphonium trifluoromethanesulfinate
Bis(triphenyl)oxodiphosphonium
trifluoromethanesulfinate
The synthetic utility of the trifluoromethanesulfonyl (triflyl)
group as an effective oxygen activator has been extensively studied
and its many proven applications are well documented.1 Among
such applications, the conversion of triphenylphosphine oxide into
bis(triphenyl)oxodiphosphonium trifluoromethanesulfonate for
use as a general oxygen activator has attracted interest, particu-
larly from the Hendrickson group.2 They demonstrated that tri-
phenylphosphine oxide reacts smoothly under very mild reaction
conditions with triflic anhydride to afford the bis(triphenyl)oxodi-
phosphonium trifluoromethanesulfonate salt (1), currently known
as Hendrickson’s reagent (Scheme 1, Eq. 1). The structure was
erroneously assigned as the triphenyl(trifluoromethylsulfonyl-
oxy)phosphonium trifluoromethanesulfonate salt and was later
corrected by Aaberg et al.2,3 The oxodiphosphonium salt 1 was
found to undergo rapid complexation with a wide range of oxygen-
ated substrates and was capable of dehydrating alcohols, amides
and aldoximes, and activating carboxylic acids towards nucleo-
philic attack.4 Unfortunately, further exploration of the full syn-
thetic potential of 1, or variations thereof, as mild electrophilic
activators was not aggressively pursued. Only recently has the syn-
a
(Ph3P+)2O.2OTf-
Hendrickson's
reagent
(1)
(2)
Ph3P=O + Tf2O
Ph3P + Tf2O
1
b
(Ph3P+)OTf + Tf - or (Ph3P+)2O.2Tf-
2
3
Scheme 1. Reagents and conditions: (a) Ph3PO/Tf2O; 2:l stoichiometry, 0 °C,
CH2Cl2; (b) envisioned conditions for the preparation of 2: Ph3P/Tf2O; 1:l stoichi-
ometry, 0 °C or rt, CH2Cl2.
thetic utility of Hendrickson’s reagent as a mediator of thiazoline5
and imidazoline6 ring formation been highlighted by You and
Kelly6 and demonstrated by Doi and Takahashi in the total synthe-
sis of apratoxin A.7
In our quest for an economical, rapid, efficient and mild ap-
proach for the conversion of aldoximes into nitriles, we became
interested in using triphenyl(trifluoromethylsulfonyloxy)phospho-
nium trifluoromethanesulfinate (2) (Scheme 1, Eq. 2) as an alterna-
tive oxygen activator and dehydrating reagent devoid of intrinsic
nucleophiles in order to circumvent the formation of unwanted
by-products. Species released during the reaction are triphenyl-
phosphine oxide, trifluoromethanesulfonate (triflate) and trifluo-
romethanesulfinate (triflinate) ions. In principle, such a reagent
* Corresponding author. Tel./fax: + 966 4 8611190.
E-mail address: zmousa@taibahu.edu.sa (Z. Moussa).
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.01.119

Z. Moussa et al. / Tetrahedron Letters 51 (2010) 1826–1831
1827
Figure 1. 19F NMR spectra from the reaction of various equivalents of Ph3P with Tf2O in CH2Cl2 at 0 °C over a period of 10 min. (a) Ph3P (1.0 equiv) + Tf2O (1.0 equiv); (b) Ph3P
(1.1 equiv) + Tf2O (1.0 equiv); (c) Ph3P (1.2 equiv) + Tf2O (1.0 equiv); (d) Ph3P (1.3 equiv) + Tf2O (1.0 equiv).
should be accessible via reaction of readily available and inexpen-
sive triphenylphosphine (Ph3P) with an equimolar amount of triflic
anhydride. In sharp contrast to Hendrickson’s reagent (1), which is
prepared by triflating the phosphine oxide oxygen, reagent 2 is ob-
tained by direct triflation of the phosphorus atom of triphenyl-
phosphine (Scheme 1). Although reagent 2 first appeared in the
literature some time ago, its preparation, characterization, electro-
philic properties and synthetic applications remain unreported.8
We now report on the reactivity and behaviour of triphenyl-
phosphine with various amounts of triflic anhydride at different
temperatures, and the ability of the resulting complexes to act as
very strong dehydrating reagent systems for the conversion of
aldoximes into nitriles. We initially determined the appropriate
stoichiometry of triphenylphosphine to triflic anhydride required
to produce the electrophilic triphenylphosphonium salt 2 and
whether any dimerization to complex 3 would occur. This is very
critical as triflic anhydride itself is an indiscriminate electrophile
and any remaining unreacted excess will mask the true identity
of the electrophilic species responsible for dehydration. Thus, a
dichloromethane solution of triphenylphosphine (1.0 mmol) at
0 °C was treated with one molar equivalent of triflic anhydride
and the reaction progress was monitored by analyzing aliquots
by 1H, 13C, 31P and 19F NMR spectroscopy. These techniques
were complementary and proved decisive in establishing the dis-
appearance of each reagent and the emergence of new species. The
19F NMR spectrum of an aliquot taken 10 min after the addition
of triflic anhydride showed three signals at d À77.8 (s), À71.7 (s)
and À28.4 (d, J = 4.1 Hz) ppm integrating as 4.33:0.18:1.00 (Fig. 1,
spectrum a). The singlet at d À77.8 is most likely due to the triflu-
oromethanesulfinate ion and that at d À71.7 is assigned to triflic
anhydride as verified independently by the 19F (d À71.7) and 13C
NMR spectra (q, d 118.3, J = 320 Hz) of a commercial sample. The
doublet at d À28.4 was attributed to bis(triphenyl)oxodiphospho-
nium trifluoromethanesulfinate (3) (Fig. 2) as was confirmed by
44.4
44.2
44.0
-28.4
-28.5
31P-NMR
19F-NMR
O
Ph
Ph
Ph
Ph
P
Ph
Ph
Ph
+
O
CF3
F3C
P
O
S
CF3
O
S
S
P
O
51.7 ppm (s)
O -77.8 ppm (s)
Ph
Ph
-28.4 ppm
(d, J = 4.0 Hz)
O
O
44.2 ppm
(q, J = 3.9 Hz)
2
3
Figure 2. 19F and 31P NMR spectral evidence for complex 2 and the corresponding dimer 3.

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Z. Moussa et al. / Tetrahedron Letters 51 (2010) 1826–1831
other experiments (vide infra). Further evidence for the formation
of 3 stems from the 31P NMR spectrum which showed a quartet at d
44.2 (J = 4.0 Hz) (Fig. 2). The small value of the coupling constant
suggests long-range 19F–31P coupling which could only exist in
intermediate 2 or in the corresponding bis-triphenylphosphonium
dimer 3. The 31P NMR spectrum also showed another singlet at d
51.7 which was assigned to complex 2 (vide infra). Two other
unidentified and rather weak broad singlets were observed at d
75.1 and d 79.5 [(31P NMR d (integration): 44.2 (0.67), 51.7 (1),
75.1 (0.28), 79.5 (0.32)] (Fig. 3, spectrum a). The signal for Ph3P
which usually occurs at d À5.5 was not detected. Temperature con-
trol is critical as slight fluctuations led to additional new signals
emerging in the 31P NMR spectrum and others disappearing. For
example, performing the addition at À5 °C resulted in the emer-
gence of a new signal at d 61.7 and the disappearance of the broad
resonances observed at d 75.1 and d 79.5. The signals at d 44.2 and
d 51.7 remained unchanged. On the other hand, running the reac-
tion at room temperature under the same conditions resulted in
identical signals to those observed at 0 °C, although in different ra-
tios [(31P NMR d (integration): 44.2 (0.82), 51.7 (1), 75.1 (0.47),
79.5 (0.50) ppm; 19F NMR d (integration): À77.8 (4.1), À71.7
(0.20) and À28.4 (1) ppm)]. The 1H NMR spectrum of the reaction
mixture at 0 °C showed overlapping aromatic signals extending
from d 8.02–7.59, whereas the 13C DEPT-135 spectrum displayed
new aromatic signals due to the resulting complexes at d 138.6
(br s, CH), 137.4 (d, J = 4.0 Hz, CH, 2), 134.9 (d, J = 3.0 Hz, CH, 3),
134.5 (br s, CH), 134.2 (d, J = 12.0 Hz, CH, 2), 132.8 (d, J = 12.0 Hz,
CH, 3), 131.3 (d, J = 15.0 Hz, CH, 2), 131.2 (br s, CH), 129.7 (d,
J = 13.0 Hz, CH, 3), with chemical shifts that differed from those
of triphenylphosphine [137.1 (d, J = 11.0 Hz, C), 133.7 (d,
J = 20.0 Hz, 2 Â CH), 128.7 (p-CH), 128.5 (d, J = 7.0 Hz, 2 Â CH)].
The 31C NMR spectrum of the experimental sample showed a quar-
tet (d 119.3, J = 319 Hz) due to the triflinate moiety, and two other
quaternary carbons appeared as doublets at
d 123.1 (d,
J = 108.5 Hz, C, 3) and d 115.6 (d, J = 84.4 Hz, C, 2). Interestingly,
the observed large coupling constants support the presence of a
P–O bond, as a similar coupling constant was observed for the qua-
ternary carbon atom of Ph3PO (d, J = 104.2 Hz), whereas a much
smaller J value was observed for the quaternary carbon of Ph3P
(d, J = 11.0 Hz). The characteristic carbon quartet expected from
the presence of remaining triflic anhydride was not observed in
the 13C NMR spectrum. No changes were observed in the NMR
spectra when the reaction mixture was warmed to room tempera-
ture and stirred overnight.
In the next stage of our series of experiments aimed at deter-
mining the amount of Ph3P required for the complete consumption
of unreacted triflic anhydride and directed at discerning the struc-
ture of the triphenylphosphonium intermediates, 1.1 mole equiv of
Figure 3. 31P NMR spectra from the reaction of various equivalents of Ph3P with Tf2O in CH2Cl2 at 0 °C over a period of 10 min. (a) Ph3P (1.0 equiv) + Tf2O (1.0 equiv); (b) Ph3P
(1.1 equiv) + Tf2O (1.0 equiv); (c) Ph3P (1.2 equiv) + Tf2O (1.0 equiv); (d) Ph3P (1.3 equiv) + Tf2O (1.0 equiv); (e) Ph3P (2.0 equiv) + Tf2O (1.0 equiv).

Z. Moussa et al. / Tetrahedron Letters 51 (2010) 1826–1831
1829
Ph3P and triflic anhydride (1.0 mmol) was reacted at 0 °C under the
conditions used earlier. The 19F NMR spectrum of an aliquot taken
after 10 min showed the same three signals observed earlier [d
À77.8 (s), À71.7 (s) and À28.4 (d)], with an integration ratio of
4.01:0.09:1.0 (Fig. 1, spectrum b). Clearly, some triflic anhydride
remains unreacted, although it is present in a relatively smaller
amount than that observed earlier with the equimolar reaction of
both reagents. The addition of 1.2 mole equiv of Ph3P to triflic
anhydride (1.0 mmol) produced the expected three signals in the
19F NMR spectrum with an integration ratio of 3.69:0.06:1.0
(Fig. 1, spectrum c), whereas the addition of 1.3 mole equiv of
Ph3P resulted in the complete consumption of triflic anhydride
yielding two signals only [d À77.8 (s) and d À28.4 (d)] in a ratio
of 3.57:1.0 (Fig. 1, spectrum d). This clearly indicates that Ph3P
and triflic anhydride react in 1.3:1 stoichiometry as >95% of the lat-
ter was consumed immediately after the start of the reaction. It is
noted that the ratio between the two signals at d À77.8 and d
À28.4 ppm decreased consistently with additional Ph3P as is
clearly shown in spectra a–d, Figure 1. The 31P NMR spectra for
the preceding series of reactions are shown in Figure 3 and indicate
that 1.1 equiv of Ph3P produces the same four intermediates ob-
served earlier as well as traces of an as yet unidentified species
appearing upfield with a chemical shift of d 2.42 [31P NMR d (inte-
gration): 2.42 (0.08), 44.2 (0.57), 51.7 (1), 75.1 (0.25), 79.5 (0.19);
(Fig. 3, spectrum b)]. With 1.2 equiv of Ph3P, the broad singlets at
d 75.1 and d 79.5 disappeared almost completely whereas those
at d 44.2 and d 2.42 ppm experienced a reduction and enhance-
ment in integration, respectively [31P NMR d (integration): 2.42
(0.16), 44.2 (0.46), 51.7 (1); (Fig. 3, spectrum c)]. Finally, utilizing
the optimum amount of Ph3P (1.3 equiv) needed for the complete
O
S
O
S
Ph
Ph
_
_
+
+
O
O
CF3
path a
P
O
CF3
O
path a
Ph
Ph
2
4
O
O
S
CF3
Ph
Ph
P:
O
S
O
S
O
Ph
S
O
+
O
+
CF3
Ph
Ph
P
CF3
path b
path b
F3C
O
O
Scheme 2. Plausible pathways for the reaction of Ph3P with Tf2O.
Figure 4. 31P NMR reaction profile for the conversion of 2,6-dichlorobenzaldehyde oxime into 2,6-dichlorobenzonitrile under the conditions given in Table 1; (a) Ph3P
(1.3 equiv) + Tf2O (1.0 equiv), 0 °C, 10 min; (b) 2,6-dichlorobenzaldehyde oxime (1.0 equiv) was added to the reaction mixture at 0 °C; (c) the reaction mixture was treated
with Et3N (2 equiv).

1830
Z. Moussa et al. / Tetrahedron Letters 51 (2010) 1826–1831
Table 1
reaction of triflic anhydride resulted in the same three signals ob-
served above [31P NMR d (integration): 2.42 (0.24), 44.2 (0.40), 51.7
(1); (Fig. 3, spectrum d)]. It is noted from Figure 3 that as the
amount of Ph3P was increased, there was a consistent reduction
in the integration of the signal at d 44.2 and an apparent enhance-
ment of that at d 2.42. The 1H NMR spectrum of the reaction mix-
ture exhibited chemical shifts ranging from d 8.02–7.59, whereas
the 13C DEPT-135 spectrum displayed, in addition to the usual
six aromatic CH doublets of 2 and 3, three new aromatic CH dou-
blets stemming from the minor compound with a 31P chemical
shift of d 2.42 ppm [13C NMR d 135.5 (d, J = 3.0 Hz, CH), 134.0 (d,
J = 10.0 Hz, CH), 130.5 (d, J = 15.0 Hz, CH)].
The final reaction of our series of experiments at 0 °C involved
treating triflic anhydride (1.0 mmol) with 2 equiv of Ph3P and ana-
lyzing an aliquot of the reaction mixture after 10 min by NMR.
Spectrum e of Figure 3 clearly shows that the excess Ph3P reacted
completely as demonstrated by the absence of a signal at d À5.41.
The signal for complex 2 was virtually undetectable as the 31P NMR
spectrum showed a major signal for dimer 3 and a minor one for
the species which was observed earlier at d 2.42 (integration;
1.00:0.33, respectively). The 19F NMR spectrum showed the two
signals at d À77.8 (s) and d À28.4 (d) and indicated that triflic
anhydride had been totally consumed, whereas the 13C NMR spec-
trum demonstrated the expected signals as observed earlier for the
above-mentioned two products. The disappearance of 2 is under-
standable as excess Ph3P converts it into the corresponding bis(tri-
phenyl)oxodiphosphonium dimer 3. It is worthwhile noting that
when the same reaction was conducted at room temperature, the
same two species were formed in almost similar ratios.
We believe that 2 is formed by the attack of the phosphorus
atom of triphenylphosphine on the anhydride oxygen of triflic
anhydride via path a of Scheme 2, releasing a trifluoromethanesulf-
inate ion as the leaving group. Triphenylphosphine can also be
envisioned to undergo an alternative reaction pathway (path b)
in which it reacts with the triflyl group to give an electrophilic tri-
phenyl(trifluoromethylsulfonyl)phosphonium complex (4) and a
negative triflate ion (Scheme 2). Complex 4 may then act as a triflyl
source, negating the role of triphenylphosphine. Fortunately, this
was not the case as was proven by the reaction of Ph3P with
PhNTf2. The latter reagent is a source of a triflyl group and a very
strong triflating agent. When an equimolar amount of Ph3P and
PhNTf2 was reacted in CH2Cl2 at 0 °C, the former failed to react
as was demonstrated by 1H, 13C, 19F and 31P NMR spectroscopy.
For example, the 31P NMR spectrum showed only one signal at d
À5.41 due to Ph3P, and the 19F NMR spectrum contained one signal
at d À70.6 corresponding to PhNTf2.
Nitriles prepared from aldoximes via reaction with the Ph3P/Tf2O reagent systema
Ph3P (1.3 mmol), Tf2O (1.0 mmol)
R
C N
RCH=N-OH
Et3N (2 mmol), CH2Cl2, 0 oC, 10 min
Entry
1
Substrate
Product
Yieldb (%)
OH
OH
CN
N
91
CN
N
2
3
4
95
98
92
OMe
OMe
OH
CN
N
MeO
MeO
OH
CN
N
CF3O
CF3O
OH
CN
N
5
6
92
93
OMe
OMe
OMe
OMe
OH
CN
N
MeO
MeO
OMe
OMe
OH
CN
N
7
8
93
94
Cl
Cl
OH
CN
N
Cl
Cl
OH
CN
Cl
N
9
95
Cl
Cl
Cl
Cl
Cl
OH
OH
CN
N
N
10
11
12
95
93
95
Cl
Cl
CN
Cl
Cl
Cl
Cl
Cl
Cl
Next, we assessed the electrophilic properties of the Ph3P/Tf2O
reagent system and its effectiveness as a general oxygen activator.
2,6-Dichlorobenzaldehyde oxime was used as a model compound
in a complexation/dehydration study with the Ph3P/Tf2O reagent
system and the progress of the reaction was monitored by 31P
NMR spectroscopy. The reagent system was prepared under the
optimal conditions reported earlier (Fig. 4, spectrum a). The oxime
(1.0 equiv) underwent immediate complexation at 0 °C with all
three species present in the reagent system to give a single com-
plex as observed in Figure 4, spectrum b. Finally, the addition of
two equivalents of Et3N resulted in immediate and clean dehydra-
tion of the oxime to the corresponding nitrile in high yield and
eliminated Ph3P@O as demonstrated in Figure 4, spectrum c.
Having established a proof of concept for the activating ability
of the Ph3P/Tf2O reagent system, the versatility of this protocol
was examined on various structurally diverse aldoximes derived
from aromatic (entries 1–17, 25 and 26), heterocyclic (entries
18–20 and 24) and aliphatic (entries 21–23) substrates (Table 1).
Using the optimized conditions (1.3:1 Ph3P/Tf2O), the dehydration
proceeded rapidly at 0 °C and produced high yields of the corre-
OH
CN
Cl
N
Cl
Cl
F
F
OH
OH
CN
13
14
96
85
N
N
Cl
CN
NO2
N
NO2
CN
OH
15
16
95
NO2
NO2
OH
CN
N
88
O2N
O2N
(continued on next page)

Z. Moussa et al. / Tetrahedron Letters 51 (2010) 1826–1831
1831
In summary, we have presented NMR evidence of the novel
triphenyl(trifluoromethylsulfonyloxy)phosphonium trifluorome-
thanesulfinate complex and its corresponding bis(triphenyl)oxodi-
phosphonium trifluoromethanesulfinate dimer which are
produced on mixing 1.3 equiv of Ph3P with Tf2O (1.0 mmol). The
electrophilic properties of the system have been utilized in the
development of a mild method for converting aldoximes into ni-
triles, rapidly at 0 °C in high yields.10 The method tolerates a wide
range of substrates and functional groups and has been shown to ex-
hibit some degree of chemoselectivity. Hence, this method should
find utility in synthesis and may prove to be a valuable alternative
to known methods.
Table 1 (continued)
Entry
Substrate
Product
Yieldb (%)
88
Cl
Cl
CN
OH
N
17
NO2
NO2
OH
N
N
CN
N
18
19
20
21
22
84
84
85
90
95
OH
CN
N
N
N
N
OH
CN
N
N
Acknowledgements
OH
CN
N
We thank Lena Moussa for helpful discussions during the
preparation of this Letter. This work was supported by the Dean-
ship of Scientific Research of Taibah University (project number:
600/1431). Dr. Ziad Moussa greatly acknowledges this generous
financial support.
N
CN
OH
OH
CN
23
24
82
60
N
O
O
CN
CN
OH
OH
N
References and notes
N
1. Hendrickson, J. B.; Sternbach, D. D.; Kenneth, W. B. Acc. Chem. Res. 1977, 10,
306–312.
25
26
84
85
OH
OH
2. Hendrickson, J. B.; Schwartzman, S. M. Tetrahedron Lett. 1975, 277–280.
3. Aaberg, A.; Gramstad, T.; Husebye, S. Tetrahedron Lett. 1979, 2263–2264.
4. Hendrickson, J. B.; Hussoin, Md. S. J. Org. Chem. 1987, 52, 4137–4139.
5. You, S.-L.; Razavi, H.; Kelly, J. W. Angew. Chem., Int. Ed. 2003, 42, 83–85.
6. You, S.-L.; Kelly, J. W. Org. Lett. 2004, 6, 1681–1683.
Br
HO
OH
Br
CN
N
HO
7. (a) Doi, T.; Numajiri, Y.; Munakata, A.; Takahashi, T. Org. Lett. 2006, 8, 531–534;
(b) Numajiri, Y.; Takahashi, T.; Doi, T. Chem. Asian J. 2009, 4, 111–125.
8. Ramos, S.; Rosen, W. Tetrahedron Lett. 1981, 22, 35–38.
Br
Br
Products were characterized by 1H and 13C NMR spectroscopy and compared
a
9. For recent publications describing the conversion of aldoximes into nitriles see:
(a) Kim, H. S.; Kim, S. H.; Kim, J. N. Tetrahedron Lett. 2009, 50, 1717–1719; (b)
Singh, M. K.; Lakshman, M. K. J. Org. Chem. 2009, 74, 3079–3084; (c) Zuidema,
D.; Dennison, A.; Park, E.; Mebane, R. Synth. Commun. 2008, 38, 3810–3815; (d)
Yoshiro, F.; Kazuaki, I.; Hisashi, Y. Bull. Chem. Soc. Jpn. 2007, 80, 400–406; (e)
Campbell, J. A.; McDougald, G.; McNab, H.; Rees, L. V. C.; Tyas, R. G. Synthesis
2007, 3179–3184; (f) Khan, T. A.; Peruncheralathan, S.; Ila, H.; Junjappa, H.
Synlett 2004, 2019–2021; (g) Ishihara, K.; Furuya, Y.; Yamamoto, H. Angew.
Chem., Int. Ed. 2002, 41, 2983–2986.
10. Typical procedure for the conversion of an aldoxime into the corresponding nitrile.
A CH2Cl2 solution (5 mL) of Ph3P (1.3 mmol) was cooled in an ice bath to 0 °C
and treated with Tf2O (1.0 mmol). After stirring the mixture for 10 min, the
aldoxime (1.0 mmol) was added as a neat liquid or solid, followed by the
addition of Et3N (2.0 mmol). After stirring for another 10 min, the mixture was
diluted with CH2Cl2 (10 mL) and washed with H2O (20 mL) and brine (20 mL).
The organic layer was dried over Na2SO4, and the residue was purified on silica
gel (elution with 5% EtOAc/hexanes) to afford the nitrile in the yields shown in
Table 1.
with authentic commercial samples. The 1H and 13C NMR spectra matched those
reported in the literature.
b
Isolated unoptimized yields.
sponding nitriles.9 The method tolerates a wide range of substrates
and functional groups such as methoxy, trifluromethoxy, halogens
and nitro. Moreover, the system exhibits some degree of chemose-
lectivity (entries 25 and 26) as the oxime function reacted prefer-
entially over the phenolic hydroxy group. Interestingly, ring-
activating and deactivating substituents had no significant effect
on the rate of reaction as all the nitriles shown in Table 1 were pro-
duced almost immediately following the addition. All the products
were characterized by 1H and 13C NMR spectroscopy and were
compared with authentic commercial samples.