1-(organoselanyl)perfluoroalkanols: A stable and efficient precursor for organoselenols

Article abstract of DOI:10.1246/cl.2008.1046

The 1-(organoselanyl)perfluoroalkanols 1, 3, 4, and 10 were successfully prepared and reactions with hexanoyl chlorides to produce the corresponding esters 5, 7, and 8, accompanied by the selenoesters 6 were conducted. The DBU-mediated alkylations of the heptafluorobutanols 4, 10, and the α-p-nitro-benzoate 2 with alkyl halides easily provided alkyl phenyl selenides 9a-9i and 11a-11c in good to high yields. Copyright

Full text of DOI:10.1246/cl.2008.1046

1046
Chemistry Letters Vol.37, No.10 (2008)
1-(Organoselanyl)perfluoroalkanols:
A Stable and Efficient Precursor for Organoselenols
Teruhisa Yamamoto, Eri Moriura, Arisa Sawa, and Mitsuhiro Yoshimatsuꢀ
Department of Chemistry, Faculty of Education, Gifu University, 1-1 Yanagido, Gifu 501-1193
(Received June 26, 2008; CL-080643; E-mail: yoshimae@gifu-u.ac.jp)
The 1-(organoselanyl)perfluoroalkanols 1, 3, 4, and 10
were successfully prepared and reactions with hexanoyl chlo-
rides to produce the corresponding esters 5, 7, and 8, accompa-
nied by the selenoesters 6 were conducted. The DBU-mediated
alkylations of the heptafluorobutanols 4, 10, and the ꢀ-p-nitro-
benzoate 2 with alkyl halides easily provided alkyl phenyl
selenides 9a–9i and 11a–11c in good to high yields.
Rf
Rf
i
+
OCO(CH2)4Me PhSeCO(CH2)4Me
OH
PhSe
PhSe
5 (Rf = CF3)(55%)
7 (Rf = CF2CF3)(43%)
8 (Rf = CF2CF2CF3)(15%)
1
3
4
6 (17%)
6 (49%)
6 (68%)
Reagent: i, Me(CH2)4COCl (1.2 equiv), pyridine (1.0 equiv), DMAP
(0.1 equiv), CH2Cl2, 0 oC, 10 min
Scheme 2. Reactions of 1-(phenylselanyl)perfluoroalkanols 1,
3, and 4 with hexanoyl chloride.
1-Organoselanylalkanols (1-organoselanyl hemiacetals) are
recognized as labile intermediates in the syntheses of 1,1-bis-
(organoselanyl)alkanes (Se,Se-acetals) (Figure 1).1 The corre-
sponding sulfur analogs were reported to be isolated as 2,2,2-tri-
fluoro-1-(organosulfanyl)ethanol by hydrolysis of the acetate;
however, the yield of the product was very low.2 Since a conven-
ient and easy access to 1-organosulfanyl and selanylalkanols
(sulfanyl and selanylhemiacetals) has not been reported, we
conducted the syntheses of these analogs as perfluoroalkanols
and now report the initial results of the selenium analogs and
their unique reactivities.
selanyl group in the 1H NMR spectrum, a singlet at ꢁ 1.73 in the
19F NMR spectrum, and m=z 256 (Mþ) in the mass spectrum.
Furthermore, the hemiacetal 1 was isolated as p-nitrobenzoate
2 (mp 75–76 ꢁC). Hemiacetal 1 was also found to be very stable
both in air for 8 months and in CDCl3 for one week. We next
prepared both 2,2,3,3,3-pentafluoro-1-(phenylselanyl)propanol
(3) and 2,2,3,3,4,4,4-heptafluoro derivative 4 by almost the same
procedure,5 and performed reactions with hexanoyl chloride as
shown in Scheme 2.
First, we examined preparation of 1-(phenylselanyl)per-
fluoroalkanols as 1-organoselanyl hemiacetals (Scheme 1). We
selected trifluoroacetaldehyde ethyl hemiacetal as the commer-
cially available precursor of the selenohemiacetals and phenyl-
selanyldiisobutylaluminum3 as the soft selenium nucleophile.
The reaction proceeded over 1 h to quantitatively give 2,2,2-tri-
fluoro-1-(phenylselanyl)ethanol (1);4 however, further purifica-
tions by chromatography afforded the diphenyl diselenide. Dis-
tillation afforded almost pure hemiacetal 1, however, elemental
analysis could not be accomplished because the material con-
tained a small amount of benzeneselenol. The structure determi-
nation of 1 was based on the spectral data, which showed a dou-
blet at ꢁ 2.54 (J ¼ 9 Hz) due to the hydroxy group and a doublet
of quartets at ꢁ 5.39 (J ¼ 9 and 7 Hz) due to the ꢀ-proton of the
The reaction of trifluoroethanol 1 with hexanoyl chloride
gave the 2,2,2-trifluoro-1-(phenylselanyl)ethyl hexanoate (5) in
55% yield, accompanied by Se-phenyl hexaneselenoate 6 in
17% yield. The hexanoylation reactions of both 2,2,3,3,3-penta-
fluoropropanol 3 and 2,2,3,3,4,4,4-heptafluorobutanol 4 sur-
prised us based on the yields of the products. The yields of the
esters 5, 7, and 8 decreased as the length of the perfluoroalkyl
groups grew longer, while that of the selenoesters increased.
In particular, the yield of 6 in the reaction of 4 with hexanoyl
chloride is the highest. This tendency was observed in the reac-
tions with isobutyryl chloride, benzoyl chloride, and p-bromo-
benzoyl chloride.
The reactivity could be explained by the relative Ka of the
perfluoroalkanols 1, 3, and 4 under basic condition given in
Figure 2. Since the distillates contain a small amount of ben-
zeneselenol, the hemiacetals would be in equilibrium with both
benzeneselenol and the perfluoroalkanols. The product ratios
of the hexanoylations would be due to the acidities of the
hydroxy groups of the hemiacetals, and the 2,2,3,3,4,4,4-
heptafluorobutanol 4 was found to be useful for producing the
benzeneselenol.
R1
R3SeH
H+
R1
R2 SeR3
R3SeH
H+
SeR3
R1 SeR3
R2 OH
O
R2
Figure 1. 1-Organoselanylalkanols (1-organoselanyl hemiace-
tals).
We found that 2,2,3,3,4,4,4-heptafluorohemiacetal 4 was a
Rf
Rf
CF3
i
ii
OH
OH
OCOC6H4-p-NO2
Rf
EtO
PhSe
Rf=CF3
PhSe
PhSeH + RfCHO
OH
2
1 (Rf = CF3)
RSe
Reagent: i, i-Bu2AlSePh (1.2 equiv),
toluene, 0 oC, 1 h; ii, p-NO2C6H4COCl
(1.2 equiv), pyridine (1.0 equiv),
DMAP (0.1 equiv)
Selenol
3 (Rf = CF3CF2)
Hemiacetal
4 (Rf = CF3CF2CF2)
Ka: CF3 < CF2CF3 < CF2CF2CF3
Figure 2. Relative Ka of 1-(organoselanyl)perfluoroalkanols in
the presence of DBU.
Scheme 1. Synthesis of 1-(organoselanyl)perfluoroalkanols.
Copyright Ó 2008 The Chemical Society of Japan

Chemistry Letters Vol.37, No.10 (2008)
1047
good compound to provide benzeneselenol, therefore, we next
tried to utilize hemiacetal 4 as the precursor of benzeneselenol.
Benzeneselenol is the most common selenium compound and
is commercially available or in situ generated from diphenyl
diselenide/H3PO2 in THF–H2O; however, it is highly labile in
air and easily undergoes oxidation to form diphenyl diselenide.6
There exist many reagents providing its synthetic equivalent,
such as trimethylsilyl phenyl selenide (TMSSePh),7 tris(phenyl-
selanyl)borane (B(SePh)3),8 sodium and lithium benzeneseleno-
late PhSeM,9 i-Bu2AlSePh,3 (PhSe)2/NaBH4,10 and (PhSe)2/
LiAlH4.11 The metal organoselenolates9 have sometimes acted
as effective reducing agents, not as nucleophiles.7b Organosele-
nols generated from the hemiacetals would be a powerful tool for
the selective introduction of selenium functional groups. There-
fore, we next performed alkylations of hemiacetal 4 with alkyl
halides. First, a productive approach was to change the base in
the reaction of 4 with benzyl bromide under conditions such as
1 equiv of base at 0 ꢁC for 10 min. Reaction in the presence of
1,8-diazabicyclo[5.4.0]-7-undecene (DBU) afforded 9e in 66%
yield, however, the other bases were ineffective for the alkyla-
tion as follows: pyridine/DMAP (0.1 equiv) in 29%, 1 mol/L
NaOH in 32%, i-Pr2NEt in 49%, triethylamine in 29% yield.
Since DBU was found to be the most suitable for removing
benzeneselenol from 4, we next examined the reactions with
some alkyl halides and the results are shown in Table 1. Since
we found that aroyloxyperfluoroalkanes 2 also decomposed
in the presence of DBU, we further investigated alkylations
using 2 and obtained alkyl phenyl selenides 9c–9f and 9i in good
to high yields (Entries 11–15).
CF3CF2CF2
CF3CF2CF2
EtO
ii
i
OH
n-BuSeR
OH
n-BuSe
10 (quant.)
Reagents: i, n-BuSeAlBui2
(1.2 equiv), 0 oC, 1 h; ii, Alkyl
Halide (1 equiv), DBU (1 equiv),
rt, in Air
Alkyl Halide
BnBr
11a (R = Bn)(55%)
cinnamyl-
chloride
CH2I2
11b (R = cinnamyl)(55%)
11c (R = CH2Sen-Bu)(62%)
Scheme 3. Synthesis and alkylations of 1-butylselanyl-2,2,3,3,
4,4,4-heptafluorobutanol (10).
DBU-promoted alkylations of the hemiacetal 10 with a few alkyl
halides. Satisfactory results were obtained as shown in Scheme 3.
In summary, we have described for the first time the synthe-
ses of 1-organoselanyl hemiacetals as perfluoroalkanols, which
were isolated as alkanoyloxyalkanes or aroyloxyalkanes. The
base-promoted alkylations with alkyl halides proceeded in good
to high yields. Since the organoselenols have been attracting
much attention as novel anchoring groups of monolayers on met-
als in the chemistry of molecular electronics,12 this methodology
could be a powerful tool for providing indispensable organo-
selenols when required.
References and Notes
1
2
3
O-Trimethylsilyl ether: W. Dumont, A. Krief, Angew. Chem.
1977, 89, 559.
K. Uneyama, M. Momota, K. Hayashida, T. Itoh, J. Org.
Chem. 1990, 55, 5364.
A. P. Kozikowski, A. Ames, J. Org. Chem. 1978, 43, 2735;
K. Maruoka, T. Miyazaki, M. Ando, Y. Matsumura, S. Sakane,
K. Hattori, H. Yamamoto, J. Am. Chem. Soc. 1983, 105, 2831;
T. Inoue, T. Takeda, N. Kambe, A. Ogawa, I. Ryu, N. Sonoda,
J. Org. Chem. 1994, 59, 5824.
DBU, THF
R2R3CXn
(1 equiv)
X=Cl, Br, I
R2R3C(SePh)n
CF3CF2CF2
ð1Þ
OR1
9
4 (R1=H)
4
5
S. Piettre, C. De Cock, R. Merenyi, H. G. Viehe, Tetrahedron
1987, 43, 4309.
PhSe
2 (R1=p-NO2C6H4CO)
4: IR (KBr) ꢂ: 3409 (OH), 1476, 1439, 1344, 1229, 1182, 1127,
We next examined the preparations of the other hemiacetal
bearing butylselanyl group (Scheme 3). Since butylselanyl de-
rivative 10 was quantitatively obtained, we also examined the
1104 (m), 965 (m), 937 (m), 733 (m), 689 (m) cmꢂ1; 1H NMR
(500 MHz, CDCl3, 26 ꢁC, TMS) ꢁ 2.6 (1H, d, J(H,H) ¼ 7 Hz,
2
2
2
OH), 5.6 (1H, dd, J(H,H) ¼ 9 Hz and J(H,F) ¼ 23 Hz, CH),
7.2–7.5 (3H, m, ArH), 7.6–7.7 (2H, m, ArH); 19F NMR
(470.5 MHz, CDCl3, CF3CO2H) ꢁ ꢂ3:1 (3F, s, CF3), ꢂ34:2
Table 1. Base-mediated alkylation of 2,2,3,3,4,4,4-heptafluoro-
butanol 4 and p-nitrobenzoate 2
2
2
(1F, d, J(F,F) ¼ 279 Hz, CF2), ꢂ45:9 (1F, d, J(F,F)
¼
Acetal
(equiv)
Alkyl halide
R2R3CXn
Yield of
9/%c
2
Conditionsa,b
279 Hz, CF2), ꢂ46:7 (1F, d, J(F,F) ¼ 296 Hz, CF2), ꢂ48:3
Run
2
(1F, d, J(F,F) ¼ 296 Hz, CF2); MS (70 eV): m=z (%): 355
(20) [Mþ ꢂ 1], 149 (100).
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
4 (1)
4 (1)
4 (1)
4 (1)
4 (1)
4 (1)
4 (1)
4 (1)
4 (2)
4 (3)
2 (1)
2 (1)
2 (1)
2 (1)
2 (2)
MeI
EtI
i-PrI
n-BuI
BnBr
rt, 2 h
9a (68)
9b (56)
9c (86)
9d (quant)
9e (91)
9f (84)
9g (64)
9h (54)
9i (70)
9j (66)
9c (59)
9d (64)
9e (quant)
9f (68)
9i (56)
rt, 10 min
rt, 0.5 h
rt, 15 min
0 ꢁC, 1 h
6
7
A. Chieffi, J. V. Comasseto, in Organoselenium Chemistry, ed.
by T. G. Back, Wiley, New York, 1999, Chap. 7, p. 145.
M. R. Detty, Tetrahedron Lett. 1978, 19, 5087; D. Liotta,
P. B. Paty, J. Johnston, G. Zima, Tetrahedron Lett. 1978,
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(E)-cinnamyl chloride 0 ꢁC, 1 h
8
9
D. L. J. Clive, S. M. Menchen, J. Org. Chem. 1979, 44, 4279.
Na: a) D. Liotta, U. Sunay, H. Santiesteban, W. Markiewicz,
J. Org. Chem. 1981, 46, 2605. b) S. V. Ley, I. A. O’Neil,
C. M. R. Low, Tetrahedron 1986, 42, 5363. Li: c) A. B. Smith,
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Montanucci, J. Org. Chem. 1983, 48, 4289. e) F. F. Fleming,
J. J. Pak, J. Org. Chem. 1995, 60, 4299.
Allyl bromide
TMSCH2Cl
CH2I2
rt, 2 h
0 ꢁC, 0.5 h
0 ꢁC, 0.5 h
0 ꢁC, 0.5 h
rt, 30 min
rt, 1 h
CHBr3
i-PrI
n-BuI
BnBr
rt, 10 min
(E)-cinnamyl chloride 0 ꢁC, 1 h
10 M. Miyashita, M. Hoshino, A. Yoshikoshi, Tetrahedron Lett.
1988, 29, 347.
11 N. D. P. Cosford, R. F. Schinazi, J. Org. Chem. 1991, 56, 2161.
12 K. Yokota, M. Taniguchi, T. Kawai, J. Am. Chem. Soc. 2007,
129, 5818.
CH2I2
rt, 1 h
aAll reactions were carried out in air. bEquiv of DBU was shown as
follows. Entries 1–8: 1 equiv; Entry 9: 2 equiv; Entries 11–15: 3 equiv;
c
Entry 10: 3 equiv Entry 15: 6 equiv. Isolated yields of 9.
Published on the web (Advance View) September 6, 2008; doi:10.1246/cl.2008.1046