Phenylselenofluorination of alkenes and alkynes promoted by difluoroiodotoluene and diphenyldiselenide

Article abstract of DOI:10.1055/s-2004-832827

The oxidation of diphenyldiselenide with 4-iodotoluene difluoride (DFIT) in dichloromethane produces in situ an efficient phenylselenofluorinating agent of alkenes and internal alkynes.

Full text of DOI:10.1055/s-2004-832827

LETTER
2339
Phenylselenofluorination of Alkenes and Alkynes Promoted by Difluoroiodo-
toluene and Diphenyldiselenide
P
henylselenofluo
a
rination of
r
A
lkenes
b
and
A
lkynesara Panunzi, Andrea Picardi, Marco Tingoli*
Facoltà di Agraria, Università di Napoli ‘Federico II’, Via Università, 100-I-80055 Portici (Napoli), Italy
Fax +39(081)2539186; E-mail: tingoli@unina.it
Received 20 July 2004
activated phenylselenium species in situ and transfer the
Abstract: The oxidation of diphenyldiselenide with 4-iodotoluene
difluoride (DFIT) in dichloromethane produces in situ an efficient
phenylselenofluorinating agent of alkenes and internal alkynes.
fluorine ligand, avoiding the competition of other nucleo-
philes. More recently, the Motherwell group have shown
that the very old hypervalent iodine(III) reagent difluoro-
iodotoluene (DFIT) can be prepared on a multigram scale
and used in a variety of useful transformations including
selective fluorination of dithioketals,3 arylthioglyco-
sides,4 xanthate esters5 and a-phenylsulfanyl esters6 and
amides.7 Thus, following this protocol, we have prepared
the hypervalent iodine(III) difluoride [DFIT (1),
Equation 1] and used in a new experiment starting from
cyclohexene and PhSeSePh in CH2Cl2 at ambient temper-
ature. In this case by GC-MS analysis the addition product
of PhSeF species was identified as final compound, to-
gether with 4-iodotoluene coming from DFIT reduction.
Key words: alkenes, alkynes, hypervalent iodine(III) difluoride,
diphenyldiselenide, oxidation
Our recent studies established that iodine(III) reagents are
able to generate in situ both electrophilic phenylselenium
and iodonium species starting from PhSeSePh and I2, re-
spectively.1 When these reactive intermediates were pro-
duced in the presence of terminal alkenes and an oxygen-
containing nucleophile, the corresponding addition prod-
ucts, with a Markovnikov orientation, were isolated.
More recently, we have also shown that the activated
phenylselenium moiety, produced in methanol with
phenyliodine(III) bis(trifluoroacetate) (BTI), gave a,a-
dimethoxycarbonyl compounds starting from activated
and enolisable alkyl aryl ketones.2
As summarized in Equation 1, we decided to apply this
simple and new phenylselenofluorination protocol to both
olefins and disubstituted alkynes.
R
PhSe
R
R
The common feature of all the reactions cited below is the
incorporation of an oxygen-containing nucleophile via an
inter- or an intramolecular pathway. Now it should be of
interest to evaluate the possibility of using our easily ac-
cessible and mild source of electrophilic phenylselenium
and iodonium species to develop new addition reactions,
employing different types of nucleophiles.
R
F
PhSeSePh
+ 4-Iodotoluene
4-Tol-IF2 (1, DFIT)
PhSe
R
R
F
CH2Cl2, r.t.
R
R
Equation 1
In particular, the controlled introduction of one fluorine
atom into organic molecules continues to be a challenge
for organic chemists. Thus, we have tried to use BTI and
PhSeSePh in the presence of an external source of fluorine
anions, like the commercial available Et3N·3HF, in
CH2Cl2 and choosing cyclohexene as starting material. An
equimolecular amount of both hydroxy and fluorinated
phenylselenylated cyclohexane are identified by GC-MS
as final products. Two competitive reactions clearly oc-
curred and the phenylselenonium intermediate thus
formed is consumed both by the iodine(III) ligand
CF3COO, that easily hydrolyzes to OH, and by the F-an-
ion initially added. On the basis of this experience, we
moved our attention to a fluorinating agent based on the
hypervalent iodoarene difluoride structure. This type of
compounds should in principle be able to generate the
It is important to note that the addition of PhSeF elements
to unsaturated compounds has some precedents in the lit-
erature.8 The more recent contribution to this subject
showed that the formal addition of PhSeF across the car-
bon-carbon double or triple bonds can be performed by
using N-phenylselenophthalimide and pyridine–HF or
Et3N·3HF complexes.9 Similar results have been obtained
via electrolytic fluorination of diphenyldiselenide again in
the presence of Et3N·3HF.10
Our method seems to be promising and efficient com-
pared to those described in the literature. In fact DFIT
quickly oxidizes diphenyldiselenide at room temperature
and the subsequent addition of the starting unsaturated
compound coincides with the complete decoloration of
the red-brown solution and all the reactions carried out
were completed in less than two hours.
SYNLETT 2004, No. 13, pp 2339–2342
0
3
.1
1
.2
0
0
4
Advanced online publication: 28.09.2004
DOI: 10.1055/s-2004-832827; Art ID: G27704ST
© Georg Thieme Verlag Stuttgart · New York

2340
B. Panunzi et al.
LETTER
As depicted in Table 1, various kinds of alkenes were sub- a-configuration for the anomeric fluorides and a manno-
jected to the phenylselenofluorination reaction and high stereochemistry for the PhSe linked to C-2 in both com-
stereo- and regioselectivity can be realized. In particular, pounds 6a and 7a.12
very good results are obtained on starting from different
The success of our reaction is confirmed by the result ob-
kinds of protected glycals (entry 6, 7 and 8, Table 1).
tained on starting from a phenol derivative (entry 9,
These compounds are indeed good precursors for the
Table 1). Although yield of addition product was not so
preparation of 2-phenylseleno-1-fluoro glycosyl donors
high, unprotected eugenol was easily transformed into ad-
like 6a, recently proposed as a useful intermediate in the
dition product 9a, without touching the remote phenol
group. This last compound is an interesting precursor of
total synthesis of Everninomicin 13,384-1.11
The anti-addition of PhSeF elements to protected glycals monofluoro analog of eugenol methyl ether, an extremely
3
is confirmed by observing the low value of the JHH potent and specific attractant for the oriental fruit fly, a
coupling constant (below of 2 Hz) between H1 and H2 on major pest of a wide variety of plant species.13
1H NMR of products 6a, 7a and 8a. These data suggest an
Table 1 Phenylselenofluorination of Alkenes Promoted by Difluoroiodotoluene (DFIT) and PhSeSePh in CH2Cl2 at 25 °C15
Entry
1
Alkene
Reaction products
Yield (%)a
58
cis-Stilbene
1a
Ph
Ph
F
SePh
F
2
3
1-Octene
2a
3a
65
60
SePh
C6H13
(E)-4-Octene
F
C3H7
C3H7
SePh
F
4
Cyclohexene
4a
78
SePh
F
5
6
Cyclooctene
5a
72
67
SePh
OBn
Tri-O-benzyl-D-glucal
6a16
O
BnO
F
BnO
SePh
OAc
7
3,4,6-Tri-O-acetyl-D-glucal
7a
81
O
F
AcO
AcO
SePh
8
9
3,4-Di-O-acetyl
6-deoxy-L-glucal
8a
70
62
O
F
AcO
SePh
AcO
Eugenol
9a16
HO
MeO
F
SePh
a Yields based on 19F NMR using trifluoromethylbenzene as internal standard.
Synlett 2004, No. 13, 2339–2342 © Thieme Stuttgart · New York

LETTER
Phenylselenofluorination of Alkenes and Alkynes
2341
(3) Motherwell, W. B.; Wilkinson, J. A. Synlett 1991, 191.
(4) Caddick, S.; Gazzard, L.; Motherwell, W. B.; Wilkinson, J.
A. Tetrahedron 1996, 52, 149.
(5) Koen, M. J.; Le Guyader, F.; Motherwell, W. B. J. Chem.
Soc., Chem. Commun. 1995, 1241.
(6) Greaney, M. F.; Motherwell, W. B.; Tocher, D. A. J. Chem
Soc., Perkin Trans. 1 2002, 2809.
(7) Edmunds, J. J.; Greaney, M. F.; Motherwell, W. B.; Steed, J.
W. J. Chem Soc., Perkin Trans. 1 2002, 2816.
(8) (a) Tomoda, S.; Usuki, Y. Chem. Lett. 1989, 1235.
(b) Lermontov, S. A.; Zavorin, S. I.; Pushin, A. N.;
Chekhlov, A. N.; Zefirov, N. S.; Stang, P. J. Tetrahedron
Lett. 1993, 34, 703.
We finally have extended the methodology described
above to some simple alkynyl derivatives. Concerning
these substrates we were not completely surprised to ob-
serve that also the couple DFIT/PhSeSePh acts as simple
PhSe-donor for terminal alkynes. Thus as we have ob-
served early by using BTI/PhSeSePh, phenyl acetylene
underwent only hydrogen substitution by PhSe group and
no addition of PhSeF elements to the triple bond were de-
tected. This result clearly indicates that the reactivity of
terminal alkynes with PhSeSePh and I(III) species is inde-
pendent of the structure of hypervalent iodine used.14
(9) Saluzzo, C.; La Spina, A. M.; Picq, D.; Alvernhe, G.; Anker,
D.; Wolf, D.; Haufe, G. Bull. Soc. Chim. Fr. 1994, 131, 831.
(10) Uneyama, K.; Hiraoka, S.; Amii, H. J. Fluorine Chem. 2000,
102, 215.
(11) Nicolaou, K. C.; Fylaktakidou, K. C.; Mitchell, H. J.; van
Delft, F. L.; Rodriguez, R. M.; Conley, S. R.; Jin, Z. Chem.–
Eur. J. 2000, 6, 3166.
On the other hand, internal alkynes gave the expected
trans-addition of PhSeF elements and, as depicted in
Table 2, all the substrates employed were transformed at
room temperature, in less than two hours, into the corre-
sponding substituted alkenes showing E-configuration on
double bonds.
(12) (a) Unfortunately spectroscopic properties of compound 6a
were not reported in ref.11. Nevertheless, some analogs of
our compounds 6a and 7a (Table 1) were recently described
by: Cumpstey, I.; Fairbanks, A. J.; Redgrave, A. J. Org. Lett.
2001, 3, 2371. (b) The first one is the 2-O-acetyl-3,4,6-tri-
O-benzyl-b-D-glucopyranosyl fluoride that shows in its 1H
NMR spectrum a J1,2 between H-1 and H-2 of 6.1 Hz, while
the second one named 2-O-acetyl-3,4,6-tri-O-benzyl-a-D-
mannopyranosyl fluoride shows a J1,2 of 1.9 Hz beween H-1
nd H-2. This last value of J1,2 is consistent with our data.
(13) Khrimian, A. P.; De Milo, A. B.; Waters, R. M.; Liquido, N.
J.; Nicholson, J. M. J. Org. Chem. 1994, 59, 8034.
(14) Tingoli, M.; Tiecco, M.; Testaferri, L.; Temperini, A.
Tetrahedron 1995, 51, 4691.
The use of these last interesting stereo defined substrates
as precursors of tetra-substituted olefins synthesis by us-
ing organometallic-mediated coupling reactions is under
investigation in our laboratory.
Table 2 Phenylselenofluorination of Alkenes Promoted by
Difluoroiodotoluene (DFIT) and PhSeSePh in CH2Cl2 at 25 °C15
Entry Alkyne
Reaction products
Yield
(%)a
1
2
3-Hexyne
1b16 74
F
(15) A Typical Procedure for the Phenylselenofluorination
Reaction Promoted by DFIT and PhSeSePh in CH2Cl2.
Diphenyldiselenide (0.16 mmol) was dissolved in CH2Cl2 (3
mL) in a 20 mL polyethylene erlenmeyer flask and DFIT
(0.40 mmol) was added under stirring in Ar atmosphere. The
initially yellow solution turns to a red-brown color in a few
minutes. After 15 min a CH2Cl2 solution (3 mL) of the
starting material (0.30 mmol) was added slowly. The color
of the solution disappeared in a few minutes and all the
reactions described on alkenes were completed in less than
90 min. All compounds described in Table 1, separated from
organic layers previously washed with aq NaHCO3, brine
and dried over anhyd Na2SO4, do not tolerate acidic
conditions and cannot be purified by a traditional column
chromatography on silica gel. On the other hand, fast flash
chromatography (mixture of light petroleum/tert-butyl
methyl ether) can be successfully used to remove 4-
iodotoluene and to obtain acceptable quantity of all
compounds showing high level of purity useful for
spectroscopic identification. As matter of fact, authors of
ref.6 have isolated compound 6a and used it as glycosyl
donor without any further purification. Spectral data of
compounds 4a and 5a are identical with those reported in the
literature.9 The reaction conditions resumed above have
been applied to alkynes. All the reactions reported in Table 2
are completed in less than 120 min and the crude materials
isolated are successfully purified by flash chromatography
(light petroleum/tert-butyl methyl ether) to obtain pure
compounds. Products 2b, 3b, 4b have spectral data identical
with those reported in the literature.9
SePh
F
4-Octyne
2b
78
C3H7
C3H7
SePh
F
3
4
Diphenylacetylene
1-Phenyl-1-propyne
3b
4b
82
92
Ph
Ph
SePh
F
Ph
SePh
a Isolated yields after flash chromatography.
Acknowledgment
We thank Dr. Crescenzi O. for 19F NMR spectroscopic assistance.
References
(1) (a) Tingoli, M.; Tiecco, M.; Testaferri, L.; Temperini, A.
Synth. Commun. 1998, 28, 1769. (b) De Corso, A. R.;
Panunzi, B.; Tingoli, M. Tetrahedron Lett. 2001, 42, 7245.
(2) Panunzi, B.; Rotiroti, L.; Tingoli, M. Tetrahedron Lett.
2003, 44, 8753.
The chemical shift d on 19F NMR spectra are expressed in
ppm using fluoro trichloromethane as internal reference. The
presence of six natural isotopes of selenium leads to highly
Synlett 2004, No. 13, 2339–2342 © Thieme Stuttgart · New York

2342
B. Panunzi et al.
LETTER
characteristic groups of peaks for selenium-containing
fragments. The values reported below refer to the prominent
peak.
3 H), 5.5 (br s, OH), 4.8 (dm, JH,F = 47.8 Hz, 1 H), 3.8 (s, 3
H), 3.2, 2.9 (m, 4 H). 13C NMR (50 MHz, CDCl3): d = 146.3,
144.0, 133.0, 129.1, 128.1, 127.0, 122.0, 114.0, 112.0, 93.2
(d, JC,F = 175.3 Hz), 55.8, 40.1 (d, J = 21.5 Hz), 30.9 (d,
J = 23 Hz). 19F NMR (376 MHz, CDCl3/C6H5CF3): d =
–171.8 to –172.2 (m, 1 F). GC-MS (EI): m/z (%) = 340 (8)
[M+], 310 (2), 182 (9), 162 (25), 157 (30), 137 (77), 119 (15),
103 (19), 91 (31), 77 (80).
(16) Physical data of selected compounds:
Compound 6a: 1H NMR (300 MHz, CDCl3): d = 7.6–7.5 (m,
2 H), 7.4–7.2 (m, 18 H), 5.8 (dd, J = 2.4 Hz, JH,F = 51.0 Hz,
1 H), 5.0–4.9 (ABq, JAB = 10.5 Hz, 2 H), 4.8–4.5 (ABq,
JAB = 10.7 Hz, 2 H), 4.6–4.5 (ABq, JAB = 12 Hz, 2 H), 4.1–
3.9 (m, 2 H), 3.9–3.7 (m, 2 H), 3.7–3.6 (m, 1 H), 3.3 (ddd,
J = 2.4 Hz, J = 11.2 Hz, JH,F = 32.7 Hz, 1 H). 13C NMR (75
MHz, CDCl3): d = 138.0, 137.0, 134.0, 130.0, 129.0, 128.0,
108.5 (d, JC,F = 218.7 Hz), 81.0, 79.5, 76.5, 75.0, 73.0, 69.0.
19F NMR (376 MHz, CDCl3/C6H5CF3): d = –139.9 (dd,
J = 51 Hz, J = 33 Hz, 1 F). GC-MS (EI): m/z (%) = 572 (1)
[M+ – HF], 224 (1), 207(1), 161 (2), 157 (1), 105 (2), 91
(100), 77 (9).
Compound 1b: 1H NMR (200 MHz, CDCl3): d = 7.6–7.5 (m,
2 H), 7.4–7.3 (m, 3 H), 2.7 (dq, J = 7.5 Hz, JH,F = 23.0 Hz, 2
H), 2.4 (dq, J = 7.5 Hz, JH,F = 2.7 Hz, 2 H), 1.1 (t, J = 7.5 Hz,
3 H), 1.0 (t, J = 7.5 Hz, 3 H). 13C NMR (50 MHz CDCl3):
d = 164.0 (d, JC,F = 267.5 Hz), 133.0, 129.2, 127.2, 110.0 (d,
J
C,F = 21.5 Hz), 25.0 (d, JC,F = 28.9 Hz), 24.0 (d, JC,F = 7.0
Hz), 13.8, 11.8. 19F NMR (376 MHz, CDCl3/C6H5CF3):
d = –95.8 (dd, J = 23 Hz, 1 F). GC-MS (EI): m/z (%) = 258
(45) [M+], 229 (4), 183 (5), 157 (40), 137 (41), 117 (27), 55
(43), 77 (81), 73 (74), 59 (91), 51 (100).
Compound 9a: 1H NMR (200 MHz, CDCl3): d = 7.6–7.5 (m,
2 H), 7.4–7.3 (m, 3 H), 6.9 (d, J = 7.8 Hz, 1 H), 6.7, 6.6 (m,
Synlett 2004, No. 13, 2339–2342 © Thieme Stuttgart · New York